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Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma/PNET

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00392327
Recruitment Status : Active, not recruiting
First Posted : October 26, 2006
Results First Posted : August 7, 2020
Last Update Posted : August 7, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Anaplastic Medulloblastoma
Medulloblastoma
Interventions Drug: Carboplatin
Drug: Cisplatin
Drug: Cyclophosphamide
Biological: Filgrastim
Drug: Isotretinoin
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Radiation: Radiation Therapy
Drug: Vincristine Sulfate
Enrollment 379
Recruitment Details Patients (Pts) 3-21 yrs were recruited at COG institutions.The first pt was enrolled 5/23/2007, and the last pt was enrolled 4/9/2018.The study was initially open to medulloblastoma and supratentorial primitive neuroectodermal tumor (SPNET) pts, but closed for SPNET pts as of amendment #2.All pts were off treatment at the time of results reporting.
Pre-assignment Details Participants received standard therapy consisting of surgery, radiation and chemotherapy. A subset of patients was randomly assigned to receive carboplatin. A second randomization was used to randomly assign patients to receive isotretinoin. Of note, the isotretinoin randomization was stopped early due to futility.
Arm/Group Title Regimen A (Medulloblastoma Patients) Regimen B (Medulloblastoma Patients) Regimen C (Medulloblastoma Patients) Regimen D (Medulloblastoma Patients) Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Hide Arm/Group Description Medulloblastoma patients who received regimen A (no carboplatin / no isotretinoin) Medulloblastoma patients who received regimen B (carboplatin / no isotretinoin) Medulloblastoma patients who received regimen C (no carboplatin / isotretinoin) Medulloblastoma patients who received regimen D (carboplatin / isotretinoin) SPNET patients who received regimen A (no carboplatin / no isotretinoin) SPNET patients who received regimen B (carboplatin / no isotretinoin) SPNET patients who received regimen C (no carboplatin / isotretinoin) SPNET patients who received regimen D (carboplatin / isotretinoin)
Period Title: Overall Study
Started 87 93 56 58 23 19 21 22
Completed 72 74 36 42 20 14 12 11
Not Completed 15 19 20 16 3 5 9 11
Reason Not Completed
Death             1             0             1             0             0             0             0             0
Lack of Efficacy             8             8             9             6             3             3             3             3
Physician Decision             3             5             2             2             0             1             5             3
Protocol Violation             0             0             1             0             0             0             0             0
Withdrawal by Subject             3             2             4             6             0             1             1             5
Ineligible             0             4             3             2             0             0             0             0
Arm/Group Title Regimen A (Medulloblastoma Patients) Regimen B (Medulloblastoma Patients) Regimen C (Medulloblastoma Patients) Regimen D (Medulloblastoma Patients) Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients) Total
Hide Arm/Group Description Medulloblastoma patients who received regimen A (no carboplatin / no isotretinoin) Medulloblastoma patients who received regimen B (carboplatin / no isotretinoin) Medulloblastoma patients who received regimen C (no carboplatin / isotretinoin) Medulloblastoma patients who received regimen D (carboplatin / isotretinoin) SPNET patients who received regimen A (no carboplatin / no isotretinoin) SPNET patients who received regimen B (carboplatin / no isotretinoin) SPNET patients who received regimen C (no carboplatin / isotretinoin) SPNET patients who received regimen D (carboplatin / isotretinoin) Total of all reporting groups
Overall Number of Baseline Participants 87 89 53 56 23 19 21 22 370
Hide Baseline Analysis Population Description
Only eligible patients were included in the baseline characteristics results. For example, of the 93 Regimen B medulloblastoma patients, 4 were ineligible (see patient flow) and excluded from baseline measures reporting leaving 89 eligible regimen B medulloblastoma patients.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 87 participants 89 participants 53 participants 56 participants 23 participants 19 participants 21 participants 22 participants 370 participants
<=18 years
86
  98.9%
88
  98.9%
51
  96.2%
55
  98.2%
23
 100.0%
19
 100.0%
21
 100.0%
22
 100.0%
365
  98.6%
Between 18 and 65 years
1
   1.1%
1
   1.1%
2
   3.8%
1
   1.8%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
5
   1.4%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 87 participants 89 participants 53 participants 56 participants 23 participants 19 participants 21 participants 22 participants 370 participants
8.2
(3.5 to 19.2)
8.8
(3.5 to 21.2)
9.1
(3.3 to 20.1)
9
(3.4 to 19.9)
10.7
(3.1 to 18.1)
9.4
(3.5 to 16.9)
8.9
(3.1 to 17.9)
10.3
(3.0 to 17.6)
8.8
(3.0 to 21.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 87 participants 89 participants 53 participants 56 participants 23 participants 19 participants 21 participants 22 participants 370 participants
Female
22
  25.3%
29
  32.6%
15
  28.3%
21
  37.5%
13
  56.5%
10
  52.6%
12
  57.1%
12
  54.5%
134
  36.2%
Male
65
  74.7%
60
  67.4%
38
  71.7%
35
  62.5%
10
  43.5%
9
  47.4%
9
  42.9%
10
  45.5%
236
  63.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 87 participants 89 participants 53 participants 56 participants 23 participants 19 participants 21 participants 22 participants 370 participants
Hispanic or Latino
11
  12.6%
8
   9.0%
10
  18.9%
13
  23.2%
3
  13.0%
4
  21.1%
2
   9.5%
2
   9.1%
53
  14.3%
Not Hispanic or Latino
75
  86.2%
79
  88.8%
41
  77.4%
42
  75.0%
20
  87.0%
15
  78.9%
18
  85.7%
19
  86.4%
309
  83.5%
Unknown or Not Reported
1
   1.1%
2
   2.2%
2
   3.8%
1
   1.8%
0
   0.0%
0
   0.0%
1
   4.8%
1
   4.5%
8
   2.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 87 participants 89 participants 53 participants 56 participants 23 participants 19 participants 21 participants 22 participants 370 participants
American Indian or Alaska Native
0
   0.0%
1
   1.1%
1
   1.9%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.8%
0
   0.0%
3
   0.8%
Asian
1
   1.1%
4
   4.5%
3
   5.7%
1
   1.8%
0
   0.0%
2
  10.5%
3
  14.3%
0
   0.0%
14
   3.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
12
  13.8%
7
   7.9%
5
   9.4%
0
   0.0%
9
  39.1%
2
  10.5%
3
  14.3%
8
  36.4%
46
  12.4%
White
63
  72.4%
69
  77.5%
38
  71.7%
49
  87.5%
13
  56.5%
13
  68.4%
10
  47.6%
12
  54.5%
267
  72.2%
More than one race
1
   1.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.3%
Unknown or Not Reported
10
  11.5%
8
   9.0%
6
  11.3%
6
  10.7%
1
   4.3%
2
  10.5%
4
  19.0%
2
   9.1%
39
  10.5%
1.Primary Outcome
Title Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma
Hide Description The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. Data below represents all molecular subgroups combined.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible medulloblastoma patients are included.
Arm/Group Title Regimen A (Medulloblastoma Patients) Regimen B (Medulloblastoma Patients) Regimen C (Medulloblastoma Patients) Regimen D (Medulloblastoma Patients)
Hide Arm/Group Description:
Medulloblastoma patients who received regimen A (no carboplatin / no isotretinoin)
Medulloblastoma patients who received regimen B (carboplatin / no isotretinoin)
Medulloblastoma patients who received regimen C (no carboplatin / isotretinoin)
Medulloblastoma patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 87 89 53 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent Probability
57.5
(43.6 to 71.4)
65.3
(52.0 to 78.6)
60.3
(47.0 to 73.6)
70.9
(57.8 to 84.0)
2.Primary Outcome
Title Percent Probability of Event-free Survival (EFS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
Hide Description The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible SPNET patients are included.
Arm/Group Title Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Hide Arm/Group Description:
SPNET patients who received regimen A (no carboplatin / no isotretinoin)
SPNET patients who received regimen B (carboplatin / no isotretinoin)
SPNET patients who received regimen C (no carboplatin / isotretinoin)
SPNET patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 23 19 21 22
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent Probability
52.2
(32.6 to 71.8)
52.6
(31.2 to 74.0)
19
(3.9 to 34.1)
63
(43.0 to 83.0)
3.Secondary Outcome
Title Tumor Response to Radiation Therapy for Patients With Medulloblastoma
Hide Description Percentages of patients with responses after radiation therapy (induction therapy) are reported with 95% confidence intervals. Complete and partial responses were considered responses.
Time Frame 12 weeks after treatment initiation
Hide Outcome Measure Data
Hide Analysis Population Description
83 of 87 eligible Arm A medulloblastoma patients were evaluated for response after induction, as were 85/89, 48/53, and 55/56 arm B, C, and D patients, respectively.
Arm/Group Title Regimen A (Medulloblastoma Patients) Regimen B (Medulloblastoma Patients) Regimen C (Medulloblastoma Patients) Regimen D (Medulloblastoma Patients)
Hide Arm/Group Description:
Medulloblastoma patients who received regimen A (no carboplatin / no isotretinoin)
Medulloblastoma patients who received regimen B (carboplatin / no isotretinoin)
Medulloblastoma patients who received regimen C (no carboplatin / isotretinoin)
Medulloblastoma patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 83 85 48 55
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
75.9
(65.3 to 84.6)
78.8
(68.6 to 86.9)
72.9
(58.2 to 84.7)
81.8
(69.1 to 90.9)
4.Secondary Outcome
Title Tumor Response to Radiation Therapy for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
Hide Description Percentages of patients with responses after radiation therapy (induction therapy) are reported with 95% confidence intervals. Complete and partial responses were considered responses. SPNET is no longer recognized by WHO (World Health Organization) as a disease entity. Additional trial information can be found under PubMed® # 30332335.
Time Frame 12 weeks after treatment initiation
Hide Outcome Measure Data
Hide Analysis Population Description
23 of 23 eligible Arm A SPNET patients were evaluated for response after induction, as were 18/19, 21/21, and 19/22 arm B, C, and D patients, respectively.
Arm/Group Title Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Hide Arm/Group Description:
SPNET patients who received regimen A (no carboplatin / no isotretinoin)
SPNET patients who received regimen B (carboplatin / no isotretinoin)
SPNET patients who received regimen C (no carboplatin / isotretinoin)
SPNET patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 23 18 21 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
69.9
(47.1 to 86.8)
83.3
(58.6 to 96.4)
66.7
(43.0 to 85.4)
73.7
(48.8 to 90.9)
5.Secondary Outcome
Title Percent Probability of Overall Survival (OS) for Patients With Medulloblastoma
Hide Description The Kaplan-Meier method will be used to estimate 5-year OS, defined as the time from study enrollment to death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. Data below represents all molecular subgroups combined.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible medulloblastoma patients are included.
Arm/Group Title Regimen A (Medulloblastoma Patients) Regimen B (Medulloblastoma Patients) Regimen C (Medulloblastoma Patients) Regimen D (Medulloblastoma Patients)
Hide Arm/Group Description:
Medulloblastoma patients who received regimen A (no carboplatin / no isotretinoin)
Medulloblastoma patients who received regimen B (carboplatin / no isotretinoin)
Medulloblastoma patients who received regimen C (no carboplatin / isotretinoin)
Medulloblastoma patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 87 89 53 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent Probability
66.0
(52.7 to 79.3)
75.9
(64.1 to 87.7)
69.9
(57.1 to 82.1)
81.6
(70.8 to 92.4)
6.Secondary Outcome
Title Percent Probability of Overall Survival (OS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
Hide Description The Kaplan-Meier method will be used to estimate 5-year OS, defined as the time from study enrollment to death from any cause, or to date of last contact.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible SPNET patients are included.
Arm/Group Title Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Hide Arm/Group Description:
SPNET patients who received regimen A (no carboplatin / no isotretinoin)
SPNET patients who received regimen B (carboplatin / no isotretinoin)
SPNET patients who received regimen C (no carboplatin / isotretinoin)
SPNET patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 23 19 21 22
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent Probability
60.9
(41.7 to 80.1)
57.9
(35.8 to 80.0)
35.3
(15.7 to 54.9)
77.0
(59.4 to 94.6)
7.Secondary Outcome
Title The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients
Hide Description Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 9+/-3 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
Time Frame 6 - 12 months post diagnosis
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible medulloblastoma patients are included.
Arm/Group Title Regimen A (Medulloblastoma Patients) Regimen B (Medulloblastoma Patients) Regimen C (Medulloblastoma Patients) Regimen D (Medulloblastoma Patients)
Hide Arm/Group Description:
Medulloblastoma patients who received regimen A (no carboplatin / no isotretinoin)
Medulloblastoma patients who received regimen B (carboplatin / no isotretinoin)
Medulloblastoma patients who received regimen C (no carboplatin / isotretinoin)
Medulloblastoma patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 22 30 13 23
Mean (Standard Deviation)
Unit of Measure: Score on a scale
96.6  (20.54) 89.1  (17.45) 83.5  (15.22) 94.8  (16.88)
8.Secondary Outcome
Title The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients
Hide Description Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 30+/-6 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
Time Frame 24 - 36 months post diagnosis
Outcome Measure Data Not Reported
9.Secondary Outcome
Title The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients
Hide Description Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 60+/-12 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
Time Frame 48 - 72 months post diagnosis
Outcome Measure Data Not Reported
10.Secondary Outcome
Title The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for SPNET Patients
Hide Description Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 9+/-3 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
Time Frame 6 - 12 months post diagnosis
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible SPNET patients are included.
Arm/Group Title Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Hide Arm/Group Description:
SPNET patients who received regimen A (no carboplatin / no isotretinoin)
SPNET patients who received regimen B (carboplatin / no isotretinoin)
SPNET patients who received regimen C (no carboplatin / isotretinoin)
SPNET patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 7 4 9 7
Mean (Standard Deviation)
Unit of Measure: Score on a scale
84.6  (9.66) 80.3  (28.86) 99.3  (16.33) 90.6  (21.9)
11.Secondary Outcome
Title The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for SPNET Patients
Hide Description Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 30+/-6 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
Time Frame 24 - 36 months post diagnosis
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible SPNET patients are included
Arm/Group Title Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Hide Arm/Group Description:
SPNET patients who received regimen A (no carboplatin / no isotretinoin)
SPNET patients who received regimen B (carboplatin / no isotretinoin)
SPNET patients who received regimen C (no carboplatin / isotretinoin)
SPNET patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 4 2 3 6
Mean (Standard Deviation)
Unit of Measure: Score on a scale
83.3  (9.98) 57.5  (2.12) 83.7  (4.04) 88.5  (20.95)
12.Secondary Outcome
Title The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for SPNET Patients
Hide Description Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 60+/-12 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
Time Frame 48 - 72 months post diagnosis
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible SPNET patients are included.
Arm/Group Title Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Hide Arm/Group Description:
SPNET patients who received regimen A (no carboplatin / no isotretinoin)
SPNET patients who received regimen B (carboplatin / no isotretinoin)
SPNET patients who received regimen C (no carboplatin / isotretinoin)
SPNET patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 5 1 2 3
Mean (Standard Deviation)
Unit of Measure: score on a scale
94.8  (15.55) 48.0 [1]   (NA) 87.0  (5.66) 79.7  (25.01)
[1]
There is only one data available
13.Secondary Outcome
Title Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients
Hide Description Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
Time Frame 6 - 12 months post diagnosis
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible medulloblastoma patients are included.
Arm/Group Title Regimen A (Medulloblastoma Patients) Regimen B (Medulloblastoma Patients) Regimen C (Medulloblastoma Patients) Regimen D (Medulloblastoma Patients)
Hide Arm/Group Description:
Medulloblastoma patients who received regimen A (no carboplatin / no isotretinoin)
Medulloblastoma patients who received regimen B (carboplatin / no isotretinoin)
Medulloblastoma patients who received regimen C (no carboplatin / isotretinoin)
Medulloblastoma patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 20 27 11 17
Mean (Standard Deviation)
Unit of Measure: T-Score
50.9  (11.32) 50.2  (11.92) 50.8  (10.04) 47.5  (8.25)
14.Secondary Outcome
Title Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients
Hide Description Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported. SPNET is no longer recognized by WHO (World Health Organization) as a disease entity. Additional trial information can be found under PubMed® # 30332335.
Time Frame 24 - 36 months post diagnosis
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients
Hide Description Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
Time Frame 48 - 72 months post diagnosis
Outcome Measure Data Not Reported
16.Secondary Outcome
Title Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for SPNET Patients
Hide Description Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
Time Frame 6 - 12 months post diagnosis
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible SPNET patients are included.
Arm/Group Title Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Hide Arm/Group Description:
SPNET patients who received regimen A (no carboplatin / no isotretinoin)
SPNET patients who received regimen B (carboplatin / no isotretinoin)
SPNET patients who received regimen C (no carboplatin / isotretinoin)
SPNET patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 4 3 7 4
Mean (Standard Deviation)
Unit of Measure: T-Score
53.8  (15.73) 66.7  (1.53) 46.1  (8.28) 64.3  (6.5)
17.Secondary Outcome
Title Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for SPNET Patients
Hide Description Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
Time Frame 24 - 36 months post diagnosis
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible SPNET patients are included.
Arm/Group Title Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Hide Arm/Group Description:
SPNET patients who received regimen A (no carboplatin / no isotretinoin)
SPNET patients who received regimen B (carboplatin / no isotretinoin)
SPNET patients who received regimen C (no carboplatin / isotretinoin)
SPNET patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 4 2 2 4
Mean (Standard Deviation)
Unit of Measure: T-Score
53.5  (8.27) 75.5  (12.02) 64.5  (2.12) 53.5  (7.55)
18.Secondary Outcome
Title Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for SPNET Patients
Hide Description Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
Time Frame 48 - 72 months post diagnosis
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible SPNET patients are included.
Arm/Group Title Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Hide Arm/Group Description:
SPNET patients who received regimen A (no carboplatin / no isotretinoin)
SPNET patients who received regimen B (carboplatin / no isotretinoin)
SPNET patients who received regimen C (no carboplatin / isotretinoin)
SPNET patients who received regimen D (carboplatin / isotretinoin)
Overall Number of Participants Analyzed 2 1 2 3
Mean (Standard Deviation)
Unit of Measure: T-Score
56.0  (0) 64.0 [1]   (NA) 71.5  (10.61) 53.7  (21.2)
[1]
There is only one data available
Time Frame While patients were on protocol therapy (including induction, 6 cycles of maintenance and 6 cycles of continuation) or up to 10 years while in follow-up
Adverse Event Reporting Description Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
 
Arm/Group Title Regimen A (Medulloblastoma Patients) Regimen B (Medulloblastoma Patients) Regimen C (Medulloblastoma Patients) Regimen D (Medulloblastoma Patients) Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Hide Arm/Group Description Medulloblastoma patients who received regimen A (no carboplatin / no isotretinoin) Medulloblastoma patients who received regimen B (carboplatin / no isotretinoin) Medulloblastoma patients who received regimen C (no carboplatin / isotretinoin) Medulloblastoma patients who received regimen D (carboplatin / isotretinoin) SPNET patients who received regimen A (no carboplatin / no isotretinoin) SPNET patients who received regimen B (carboplatin / no isotretinoin) SPNET patients who received regimen C (no carboplatin / isotretinoin) SPNET patients who received regimen D (carboplatin / isotretinoin)
All-Cause Mortality
Regimen A (Medulloblastoma Patients) Regimen B (Medulloblastoma Patients) Regimen C (Medulloblastoma Patients) Regimen D (Medulloblastoma Patients) Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   24/87 (27.59%)      23/89 (25.84%)      22/53 (41.51%)      16/56 (28.57%)      11/23 (47.83%)      8/19 (42.11%)      14/21 (66.67%)      8/22 (36.36%)    
Hide Serious Adverse Events
Regimen A (Medulloblastoma Patients) Regimen B (Medulloblastoma Patients) Regimen C (Medulloblastoma Patients) Regimen D (Medulloblastoma Patients) Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/87 (8.05%)      11/89 (12.36%)      5/53 (9.43%)      6/56 (10.71%)      2/23 (8.70%)      0/19 (0.00%)      1/21 (4.76%)      0/22 (0.00%)    
Blood and lymphatic system disorders                 
Febrile neutropenia † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Cardiac disorders                 
Cardiac arrest † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Eye disorders                 
Retinopathy † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Gastrointestinal disorders                 
Pancreatitis † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Small intestinal obstruction † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
General disorders                 
Death NOS † 1  2/87 (2.30%)  2 0/89 (0.00%)  0 1/53 (1.89%)  1 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Infections and infestations                 
Infections and infestations - Other, specify † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Lung infection † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Peritoneal infection † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 1/23 (4.35%)  1 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Sepsis † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 1/53 (1.89%)  1 1/56 (1.79%)  1 1/23 (4.35%)  1 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Investigations                 
Neutrophil count decreased † 1  1/87 (1.15%)  1 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Platelet count decreased † 1  1/87 (1.15%)  1 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
White blood cell decreased † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Metabolism and nutrition disorders                 
Hypercalcemia † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Hyperuricemia † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0
Musculoskeletal and connective tissue disorders                 
Soft tissue necrosis lower limb † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Myelodysplastic syndrome † 1  1/87 (1.15%)  2 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify † 1  2/87 (2.30%)  2 5/89 (5.62%)  5 2/53 (3.77%)  3 0/56 (0.00%)  0 1/23 (4.35%)  1 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Treatment related secondary malignancy † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 2/53 (3.77%)  3 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Nervous system disorders                 
Central nervous system necrosis † 1  1/87 (1.15%)  1 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Depressed level of consciousness † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                 
Apnea † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 1/23 (4.35%)  1 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Dyspnea † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Hypoxia † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Respiratory failure † 1  1/87 (1.15%)  1 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Vascular disorders                 
Hematoma † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Hypotension † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
1
Term from vocabulary, CTCAEv4
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Regimen A (Medulloblastoma Patients) Regimen B (Medulloblastoma Patients) Regimen C (Medulloblastoma Patients) Regimen D (Medulloblastoma Patients) Regimen A (SPNET Patients) Regimen B (SPNET Patients) Regimen C (SPNET Patients) Regimen D (SPNET Patients)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   72/87 (82.76%)      80/89 (89.89%)      47/53 (88.68%)      52/56 (92.86%)      21/23 (91.30%)      18/19 (94.74%)      18/21 (85.71%)      18/22 (81.82%)    
Blood and lymphatic system disorders                 
Anemia † 1  43/87 (49.43%)  81 59/89 (66.29%)  106 26/53 (49.06%)  52 32/56 (57.14%)  60 16/23 (69.57%)  25 14/19 (73.68%)  35 10/21 (47.62%)  16 15/22 (68.18%)  25
Febrile neutropenia † 1  22/87 (25.29%)  38 45/89 (50.56%)  80 17/53 (32.08%)  25 21/56 (37.50%)  31 9/23 (39.13%)  9 13/19 (68.42%)  22 4/21 (19.05%)  4 8/22 (36.36%)  14
Bone marrow hypocellular † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Leukocytosis † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Hemolysis † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Cardiac disorders                 
Sinus tachycardia † 1  1/87 (1.15%)  1 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Mobitz type I † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Sinus bradycardia † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Ear and labyrinth disorders                 
Hearing impaired † 1  12/87 (13.79%)  13 11/89 (12.36%)  11 7/53 (13.21%)  16 6/56 (10.71%)  8 1/23 (4.35%)  1 2/19 (10.53%)  3 0/21 (0.00%)  0 1/22 (4.55%)  1
Tinnitus † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Middle ear inflammation † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 1/53 (1.89%)  1 1/56 (1.79%)  1 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Ear pain † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Ear and labyrinth disorders - Other, specify † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 1/53 (1.89%)  1 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Endocrine disorders                 
Hypoparathyroidism † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Hypothyroidism † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Eye disorders                 
Optic nerve disorder † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 1/53 (1.89%)  1 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Papilledema † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 1/53 (1.89%)  1 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Retinopathy † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Gastrointestinal disorders                 
Nausea † 1  13/87 (14.94%)  19 10/89 (11.24%)  12 9/53 (16.98%)  14 14/56 (25.00%)  18 3/23 (13.04%)  3 6/19 (31.58%)  11 4/21 (19.05%)  4 1/22 (4.55%)  1
Vomiting † 1  12/87 (13.79%)  18 10/89 (11.24%)  11 14/53 (26.42%)  18 8/56 (14.29%)  10 2/23 (8.70%)  2 6/19 (31.58%)  11 3/21 (14.29%)  3 5/22 (22.73%)  6
Abdominal pain † 1  4/87 (4.60%)  4 7/89 (7.87%)  7 3/53 (5.66%)  4 2/56 (3.57%)  2 1/23 (4.35%)  1 4/19 (21.05%)  6 1/21 (4.76%)  1 2/22 (9.09%)  2
Diarrhea † 1  3/87 (3.45%)  4 1/89 (1.12%)  1 1/53 (1.89%)  1 3/56 (5.36%)  3 0/23 (0.00%)  0 3/19 (15.79%)  4 0/21 (0.00%)  0 3/22 (13.64%)  3
Ileus † 1  3/87 (3.45%)  3 2/89 (2.25%)  2 2/53 (3.77%)  2 1/56 (1.79%)  1 1/23 (4.35%)  1 2/19 (10.53%)  2 1/21 (4.76%)  1 0/22 (0.00%)  0
Esophagitis † 1  2/87 (2.30%)  2 1/89 (1.12%)  1 1/53 (1.89%)  1 0/56 (0.00%)  0 1/23 (4.35%)  1 1/19 (5.26%)  1 1/21 (4.76%)  1 0/22 (0.00%)  0
Constipation † 1  2/87 (2.30%)  2 1/89 (1.12%)  1 4/53 (7.55%)  5 2/56 (3.57%)  2 0/23 (0.00%)  0 2/19 (10.53%)  2 1/21 (4.76%)  1 2/22 (9.09%)  2
Dysphagia † 1  2/87 (2.30%)  2 3/89 (3.37%)  3 0/53 (0.00%)  0 1/56 (1.79%)  2 1/23 (4.35%)  1 2/19 (10.53%)  3 0/21 (0.00%)  0 0/22 (0.00%)  0
Mucositis oral † 1  2/87 (2.30%)  2 3/89 (3.37%)  3 1/53 (1.89%)  1 7/56 (12.50%)  8 0/23 (0.00%)  0 2/19 (10.53%)  2 1/21 (4.76%)  1 0/22 (0.00%)  0
Colitis † 1  1/87 (1.15%)  1 1/89 (1.12%)  1 1/53 (1.89%)  1 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Gingival pain † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Oral pain † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Esophageal pain † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Gastroparesis † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  2 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Gastrointestinal disorders - Other, specify † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 2/56 (3.57%)  2 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Cheilitis † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 1/53 (1.89%)  1 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Dental caries † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 1/53 (1.89%)  1 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Esophageal ulcer † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Gastric hemorrhage † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Small intestinal obstruction † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Intra-abdominal hemorrhage † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Gastrointestinal pain † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Gastritis † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 1/53 (1.89%)  1 1/56 (1.79%)  1 0/23 (0.00%)  0 1/19 (5.26%)  1 1/21 (4.76%)  1 0/22 (0.00%)  0
Typhlitis † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 3/53 (5.66%)  3 0/56 (0.00%)  0 0/23 (0.00%)  0 1/19 (5.26%)  2 1/21 (4.76%)  1 0/22 (0.00%)  0
General disorders                 
Pain † 1  4/87 (4.60%)  4 7/89 (7.87%)  9 1/53 (1.89%)  1 2/56 (3.57%)  2 0/23 (0.00%)  0 1/19 (5.26%)  2 0/21 (0.00%)  0 1/22 (4.55%)  1
Fatigue † 1  3/87 (3.45%)  3 2/89 (2.25%)  2 1/53 (1.89%)  1 2/56 (3.57%)  2 1/23 (4.35%)  1 1/19 (5.26%)  2 0/21 (0.00%)  0 2/22 (9.09%)  2
Gait disturbance † 1  1/87 (1.15%)  1 2/89 (2.25%)  2 2/53 (3.77%)  2 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 2/22 (9.09%)  2
Facial pain † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Non-cardiac chest pain † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Fever † 1  0/87 (0.00%)  0 2/89 (2.25%)  3 2/53 (3.77%)  2 2/56 (3.57%)  2 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  2
Immune system disorders                 
Anaphylaxis † 1  0/87 (0.00%)  0 4/89 (4.49%)  4 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Infections and infestations                 
Infections and infestations - Other, specify † 1  11/87 (12.64%)  27 27/89 (30.34%)  45 11/53 (20.75%)  19 14/56 (25.00%)  18 9/23 (39.13%)  10 7/19 (36.84%)  9 5/21 (23.81%)  5 8/22 (36.36%)  14
Sepsis † 1  5/87 (5.75%)  5 3/89 (3.37%)  3 2/53 (3.77%)  2 2/56 (3.57%)  3 0/23 (0.00%)  0 2/19 (10.53%)  2 0/21 (0.00%)  0 0/22 (0.00%)  0
Catheter related infection † 1  4/87 (4.60%)  4 4/89 (4.49%)  4 3/53 (5.66%)  4 1/56 (1.79%)  1 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 2/22 (9.09%)  2
Enterocolitis infectious † 1  3/87 (3.45%)  3 2/89 (2.25%)  2 2/53 (3.77%)  2 2/56 (3.57%)  3 3/23 (13.04%)  3 1/19 (5.26%)  1 0/21 (0.00%)  0 1/22 (4.55%)  2
Skin infection † 1  3/87 (3.45%)  3 5/89 (5.62%)  7 1/53 (1.89%)  1 1/56 (1.79%)  1 1/23 (4.35%)  1 2/19 (10.53%)  3 0/21 (0.00%)  0 0/22 (0.00%)  0
Meningitis † 1  2/87 (2.30%)  2 0/89 (0.00%)  0 1/53 (1.89%)  1 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Device related infection † 1  2/87 (2.30%)  2 1/89 (1.12%)  2 1/53 (1.89%)  1 1/56 (1.79%)  7 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Lung infection † 1  2/87 (2.30%)  2 1/89 (1.12%)  1 1/53 (1.89%)  1 2/56 (3.57%)  2 1/23 (4.35%)  1 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Otitis media † 1  2/87 (2.30%)  2 2/89 (2.25%)  3 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 1/19 (5.26%)  2 0/21 (0.00%)  0 0/22 (0.00%)  0
Stoma site infection † 1  2/87 (2.30%)  3 4/89 (4.49%)  5 2/53 (3.77%)  3 1/56 (1.79%)  3 1/23 (4.35%)  2 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Urinary tract infection † 1  2/87 (2.30%)  2 5/89 (5.62%)  6 2/53 (3.77%)  2 2/56 (3.57%)  3 1/23 (4.35%)  1 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Appendicitis † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Upper respiratory infection † 1  1/87 (1.15%)  1 1/89 (1.12%)  1 0/53 (0.00%)  0 1/56 (1.79%)  1 1/23 (4.35%)  1 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Cranial nerve infection † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Eye infection † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Encephalomyelitis infection † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Bone infection † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 1/53 (1.89%)  1 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Pleural infection † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 1/53 (1.89%)  1 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Otitis externa † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 2/53 (3.77%)  2 1/56 (1.79%)  1 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Abdominal infection † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Lip infection † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Nail infection † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Paronychia † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Peritoneal infection † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Small intestine infection † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Bladder infection † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Mucosal infection † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 1/53 (1.89%)  1 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Soft tissue infection † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 1/53 (1.89%)  1 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Gum infection † 1  0/87 (0.00%)  0 2/89 (2.25%)  2 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Sinusitis † 1  0/87 (0.00%)  0 2/89 (2.25%)  2 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 2/19 (10.53%)  2 0/21 (0.00%)  0 0/22 (0.00%)  0
Wound infection † 1  0/87 (0.00%)  0 2/89 (2.25%)  2 1/53 (1.89%)  1 0/56 (0.00%)  0 1/23 (4.35%)  1 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Injury, poisoning and procedural complications                 
Wound dehiscence † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 2/22 (9.09%)  2
Radiation recall reaction (dermatologic) † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Injury, poisoning and procedural complications - Other, specify † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 1/23 (4.35%)  1 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Tracheal obstruction † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Dermatitis radiation † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 1/53 (1.89%)  1 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0
Investigations                 
Neutrophil count decreased † 1  52/87 (59.77%)  113 59/89 (66.29%)  143 38/53 (71.70%)  82 40/56 (71.43%)  99 14/23 (60.87%)  31 16/19 (84.21%)  43 11/21 (52.38%)  21 16/22 (72.73%)  35
White blood cell decreased † 1  49/87 (56.32%)  116 53/89 (59.55%)  124 37/53 (69.81%)  76 36/56 (64.29%)  88 12/23 (52.17%)  24 14/19 (73.68%)  35 12/21 (57.14%)  25 11/22 (50.00%)  26
Platelet count decreased † 1  45/87 (51.72%)  88 65/89 (73.03%)  133 32/53 (60.38%)  63 42/56 (75.00%)  82 14/23 (60.87%)  21 17/19 (89.47%)  44 11/21 (52.38%)  16 14/22 (63.64%)  31
Lymphocyte count decreased † 1  31/87 (35.63%)  79 32/89 (35.96%)  81 21/53 (39.62%)  44 15/56 (26.79%)  46 9/23 (39.13%)  21 10/19 (52.63%)  25 8/21 (38.10%)  18 7/22 (31.82%)  22
Weight loss † 1  10/87 (11.49%)  12 9/89 (10.11%)  11 8/53 (15.09%)  9 5/56 (8.93%)  5 6/23 (26.09%)  9 3/19 (15.79%)  3 6/21 (28.57%)  9 4/22 (18.18%)  5
Alanine aminotransferase increased † 1  2/87 (2.30%)  2 5/89 (5.62%)  5 2/53 (3.77%)  2 3/56 (5.36%)  3 0/23 (0.00%)  0 1/19 (5.26%)  3 1/21 (4.76%)  1 1/22 (4.55%)  1
Electrocardiogram QT corrected interval prolonged † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Urine output decreased † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Serum amylase increased † 1  1/87 (1.15%)  1 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 1/23 (4.35%)  1 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Investigations - Other, specify † 1  1/87 (1.15%)  1 1/89 (1.12%)  1 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Blood bilirubin increased † 1  1/87 (1.15%)  1 1/89 (1.12%)  1 1/53 (1.89%)  1 1/56 (1.79%)  2 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
GGT increased † 1  1/87 (1.15%)  1 2/89 (2.25%)  2 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 1/19 (5.26%)  2 0/21 (0.00%)  0 0/22 (0.00%)  0
CPK increased † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Hemoglobin increased † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Lipase increased † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Creatinine increased † 1  0/87 (0.00%)  0 2/89 (2.25%)  2 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Weight gain † 1  0/87 (0.00%)  0 2/89 (2.25%)  4 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Aspartate aminotransferase increased † 1  0/87 (0.00%)  0 3/89 (3.37%)  3 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 1/19 (5.26%)  1 1/21 (4.76%)  1 0/22 (0.00%)  0
Metabolism and nutrition disorders                 
Hypokalemia † 1  23/87 (26.44%)  33 29/89 (32.58%)  41 17/53 (32.08%)  27 16/56 (28.57%)  25 5/23 (21.74%)  5 9/19 (47.37%)  11 4/21 (19.05%)  4 9/22 (40.91%)  11
Anorexia † 1  19/87 (21.84%)  30 31/89 (34.83%)  46 12/53 (22.64%)  18 15/56 (26.79%)  24 3/23 (13.04%)  5 8/19 (42.11%)  14 6/21 (28.57%)  10 10/22 (45.45%)  13
Hyponatremia † 1  7/87 (8.05%)  8 8/89 (8.99%)  8 3/53 (5.66%)  4 2/56 (3.57%)  2 2/23 (8.70%)  2 2/19 (10.53%)  3 1/21 (4.76%)  1 1/22 (4.55%)  1
Dehydration † 1  6/87 (6.90%)  7 7/89 (7.87%)  7 6/53 (11.32%)  6 3/56 (5.36%)  5 2/23 (8.70%)  2 5/19 (26.32%)  8 4/21 (19.05%)  4 3/22 (13.64%)  3
Hypophosphatemia † 1  6/87 (6.90%)  7 9/89 (10.11%)  10 3/53 (5.66%)  4 5/56 (8.93%)  5 0/23 (0.00%)  0 2/19 (10.53%)  2 1/21 (4.76%)  1 3/22 (13.64%)  3
Hypomagnesemia † 1  4/87 (4.60%)  4 3/89 (3.37%)  5 4/53 (7.55%)  5 3/56 (5.36%)  3 0/23 (0.00%)  0 1/19 (5.26%)  2 0/21 (0.00%)  0 4/22 (18.18%)  6
Hypocalcemia † 1  2/87 (2.30%)  2 3/89 (3.37%)  3 3/53 (5.66%)  3 3/56 (5.36%)  3 0/23 (0.00%)  0 3/19 (15.79%)  3 1/21 (4.76%)  1 2/22 (9.09%)  2
Acidosis † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Hyperkalemia † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 1/19 (5.26%)  1 1/21 (4.76%)  1 1/22 (4.55%)  1
Hyperglycemia † 1  1/87 (1.15%)  1 6/89 (6.74%)  6 0/53 (0.00%)  0 2/56 (3.57%)  2 0/23 (0.00%)  0 1/19 (5.26%)  1 1/21 (4.76%)  1 0/22 (0.00%)  0
Hyperuricemia † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 2/56 (3.57%)  2 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Hypoalbuminemia † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 1/53 (1.89%)  1 0/56 (0.00%)  0 2/23 (8.70%)  2 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Hypertriglyceridemia † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 1/53 (1.89%)  1 1/56 (1.79%)  2 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Hypercalcemia † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 2/53 (3.77%)  3 5/56 (8.93%)  5 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 2/22 (9.09%)  4
Hypermagnesemia † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 2/56 (3.57%)  2 1/23 (4.35%)  1 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Musculoskeletal and connective tissue disorders                 
Pain in extremity † 1  1/87 (1.15%)  1 2/89 (2.25%)  2 1/53 (1.89%)  1 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Arthritis † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0
Muscle weakness upper limb † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 1/53 (1.89%)  1 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Bone pain † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Generalized muscle weakness † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Muscle weakness lower limb † 1  0/87 (0.00%)  0 2/89 (2.25%)  2 1/53 (1.89%)  1 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Back pain † 1  0/87 (0.00%)  0 2/89 (2.25%)  2 2/53 (3.77%)  2 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Tumor pain † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify † 1  1/87 (1.15%)  1 1/89 (1.12%)  2 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Nervous system disorders                 
Peripheral motor neuropathy † 1  8/87 (9.20%)  10 15/89 (16.85%)  20 6/53 (11.32%)  9 6/56 (10.71%)  8 1/23 (4.35%)  1 1/19 (5.26%)  1 3/21 (14.29%)  4 4/22 (18.18%)  8
Hydrocephalus † 1  4/87 (4.60%)  5 1/89 (1.12%)  1 1/53 (1.89%)  1 1/56 (1.79%)  1 2/23 (8.70%)  3 2/19 (10.53%)  2 0/21 (0.00%)  0 0/22 (0.00%)  0
Headache † 1  3/87 (3.45%)  3 2/89 (2.25%)  2 2/53 (3.77%)  2 0/56 (0.00%)  0 1/23 (4.35%)  1 1/19 (5.26%)  1 2/21 (9.52%)  2 2/22 (9.09%)  2
Ataxia † 1  2/87 (2.30%)  2 4/89 (4.49%)  6 0/53 (0.00%)  0 2/56 (3.57%)  2 1/23 (4.35%)  1 0/19 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0
Central nervous system necrosis † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Glossopharyngeal nerve disorder † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Depressed level of consciousness † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Peripheral sensory neuropathy † 1  1/87 (1.15%)  2 1/89 (1.12%)  1 1/53 (1.89%)  1 3/56 (5.36%)  5 0/23 (0.00%)  0 1/19 (5.26%)  1 2/21 (9.52%)  2 1/22 (4.55%)  1
Seizure † 1  1/87 (1.15%)  1 1/89 (1.12%)  1 2/53 (3.77%)  2 0/56 (0.00%)  0 1/23 (4.35%)  2 1/19 (5.26%)  1 0/21 (0.00%)  0 1/22 (4.55%)  1
Nervous system disorders - Other, specify † 1  1/87 (1.15%)  2 2/89 (2.25%)  4 2/53 (3.77%)  2 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Syncope † 1  1/87 (1.15%)  2 3/89 (3.37%)  3 1/53 (1.89%)  1 2/56 (3.57%)  2 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Vasovagal reaction † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Hypersomnia † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0
Leukoencephalopathy † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0
Intracranial hemorrhage † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Neuralgia † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Dysarthria † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Paresthesia † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  2 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Cerebrospinal fluid leakage † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Dysphasia † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 1/53 (1.89%)  1 1/56 (1.79%)  1 1/23 (4.35%)  1 1/19 (5.26%)  1 0/21 (0.00%)  0 0/22 (0.00%)  0
Aphonia † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
IVth nerve disorder † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Myelitis † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Cognitive disturbance † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0
Dizziness † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0
Encephalopathy † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0
Somnolence † 1  0/87 (0.00%)  0 2/89 (2.25%)  2 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Psychiatric disorders                 
Anxiety † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Confusion † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Psychiatric disorders - Other, specify † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Agitation † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 1/53 (1.89%)  1 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0
Depression † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 2/53 (3.77%)  2 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  2
Insomnia † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Personality change † 1  0/87 (0.00%)  0 2/89 (2.25%)  2 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Renal and urinary disorders                 
Hematuria † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 1/23 (4.35%)  1 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Proteinuria † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 1/23 (4.35%)  1 0/19 (0.00%)  0 1/21 (4.76%)  1 0/22 (0.00%)  0
Renal and urinary disorders - Other, specify † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  2 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Chronic kidney disease † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Urinary tract pain † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Cystitis noninfective † 1  0/87 (0.00%)  0 1/89 (1.12%)  1 1/53 (1.89%)  1 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Acute kidney injury † 1  0/87 (0.00%)  0 2/89 (2.25%)  2 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Reproductive system and breast disorders                 
Hematosalpinx † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Irregular menstruation † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Azoospermia † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 1/23 (4.35%)  1 0/19 (0.00%)  0 0/21 (0.00%)  0 1/22 (4.55%)  1
Respiratory, thoracic and mediastinal disorders                 
Hypoxia † 1  4/87 (4.60%)  5 2/89 (2.25%)  2 2/53 (3.77%)  2 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Pneumonitis † 1  3/87 (3.45%)  3 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Respiratory failure † 1  2/87 (2.30%)  2 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Atelectasis † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Cough † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Sore throat † 1  1/87 (1.15%)  1 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Aspiration † 1  1/87 (1.15%)  1 1/89 (1.12%)  1 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Dyspnea † 1  1/87 (1.15%)  1 1/89 (1.12%)  1 1/53 (1.89%)  1 1/56 (1.79%)  1 1/23 (4.35%)  2 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Pharyngolaryngeal pain † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 0/56 (0.00%)  0 0/23 (0.00%)  0 1/19 (5.26%)  1 0/21 (0.00%)  0 2/22 (9.09%)  2
Apnea † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  1 0/23 (0.00%)  0 0/19 (0.00%)  0 0/21 (0.00%)  0 0/22 (0.00%)  0
Bronchospasm † 1  0/87 (0.00%)  0 0/89 (0.00%)  0 0/53 (0.00%)  0 1/56 (1.79%)  2 0/23 (0.00%)  0 0/19 (0.00%)  0