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A Study Evaluating Pertuzumab (Perjeta) Combined With Trastuzumab (Herceptin) and Standard Anthracycline-based Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced, Inflammatory, or Early-stage Breast Cancer

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: NCT02132949
Recruitment Status : Active, not recruiting
First Posted : May 7, 2014
Results First Posted : April 13, 2017
Last Update Posted : January 22, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This multicenter, non-randomized, open-label, phase 2 study is designed to evaluate the safety and efficacy of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and anthracycline-based chemotherapy as neoadjuvant treatment in participants with HER2-positive locally advanced, inflammatory, or early-stage breast cancer. Each investigator will choose a treatment regimen (A or B) for all of their participants to follow. Treatment regimen A (for Cohort A) will include dose-dense doxorubicin and cyclophosphamide (ddAC), followed by paclitaxel, with pertuzumab and trastuzumab given from the start of paclitaxel. Treatment regimen B (for Cohort B) will include 5-fluorouracil, epirubicin, and cyclophosphamide (FEC), followed by docetaxel, with pertuzumab and trastuzumab given from the start of docetaxel. Participants in both cohorts will subsequently undergo surgical treatment and then resume pertuzumab and trastuzumab treatment.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: 5-Fluorouracil Drug: Cyclophosphamide Drug: Docetaxel Drug: Doxorubicin Drug: Epirubicin Drug: Paclitaxel Drug: Pertuzumab Drug: Trastuzumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 401 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Multinational, Phase II Study to Evaluate Perjeta in Combination With Herceptin and Standard Neoadjuvant Anthracycline-Based Chemotherapy in Patients With HER2-Positive, Locally Advanced, Inflammatory, or Early-Stage Breast Cancer
Actual Study Start Date : July 14, 2014
Actual Primary Completion Date : March 3, 2016
Estimated Study Completion Date : August 26, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab
ddAC: dose dense doxorubicin and cyclophosphamide. Participants will receive doxorubicin and cyclophosphamide every 2 weeks (q2w) for 4 cycles, followed by paclitaxel for 12 weeks, with pertuzumab and trastuzumab given every 3 weeks (q3w) (8 cycles of chemotherapy in total prior to surgery) from the start of paclitaxel. Following surgery, participants will receive further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Drug: Cyclophosphamide
Participants will receive cyclophosphamide 600 milligrams per square meter (mg/m^2) intravenous (IV) given on Day 1 of each cycle q2w.

Drug: Doxorubicin
Participants will receive doxorubicin 60 mg/m^2 IV on Day 1 of each cycle q2w.

Drug: Paclitaxel
Participants will receive paclitaxel 80 mg/m^2 IV given weekly.

Drug: Pertuzumab
Participants will receive pertuzumab at a loading dose of 840 milligrams (mg) IV loading dose, then 420 mg IV q3w.
Other Name: Perjeta

Drug: Trastuzumab
Participants will receive trastuzumab at a loading dose of 8 milligrams per kilogram (mg/kg) IV, then 6 mg/kg IV q3w.
Other Name: Herceptin

Experimental: Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab
FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants will receive 5-fluorouracil, epirubicin, and cyclophosphamide given q3w for 4 cycles, followed by docetaxel q3w for 4 cycles, with pertuzumab and trastuzumab given q3w (8 cycles of chemotherapy in total prior to surgery) from the start of docetaxel. Following surgery, participants will receive further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Drug: 5-Fluorouracil
Participants will receive 5-fluorouracil 500 mg/m^2 IV on Day 1 of each cycle q3w.

Drug: Cyclophosphamide
Participants will receive cyclophosphamide 600 milligrams per square meter (mg/m^2) intravenous (IV) given on Day 1 of each cycle q2w.

Drug: Docetaxel
Participants will receive docetaxel at a starting dose of 75 mg/m^2 IV for the first cycle and the dose may be escalated to 100 mg/m^2 for subsequent cycles q3w.

Drug: Epirubicin
Participants will receive epirubicin 100 mg/m^2 IV on Day 1 of each cycle q3w.

Drug: Pertuzumab
Participants will receive pertuzumab at a loading dose of 840 milligrams (mg) IV loading dose, then 420 mg IV q3w.
Other Name: Perjeta

Drug: Trastuzumab
Participants will receive trastuzumab at a loading dose of 8 milligrams per kilogram (mg/kg) IV, then 6 mg/kg IV q3w.
Other Name: Herceptin




Primary Outcome Measures :
  1. Percentage of Participants With New York Heart Association (NYHA) Class III and IV Heart Failure During the Neoadjuvant Treatment Period [ Time Frame: Baseline to 24 weeks ]
    Symptomatic left ventricular systolic dysfunction (LVSD) is defined as heart failure. NYHA classifies participants' heart failure condition based on the participant's symptoms. Class III: marked limitation of the physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. 95 percent (%) confidence intervals (CIs) are calculated with the use of the Clopper-Pearson method.

  2. Percentage of Participants With Drop in Left Ventricular Ejection Fraction (LVEF) of at Least 10 Percentage Points From Baseline and to Below 50% During the Neoadjuvant Treatment Period [ Time Frame: Baseline to 24 weeks ]
    A confirmed event was defined as at least two consecutive readings of declines in LVEF. 95% CIs are calculated with the use of the Clopper-Pearson method.


Secondary Outcome Measures :
  1. Percentage of Participants With NYHA Class III and IV Heart Failure During the Adjuvant Treatment Period at Primary Completion Date (03 March 2016) [ Time Frame: Cycle 9 to Cycle 21 (cycle length=3 weeks; up to approximately 8 months) up to clinical cut-off date, 03 March 2016 (Month 20) ]
    LVSD is defined as heart failure. NYHA classifies participants' heart failure condition based on the participant's symptoms. Class III: marked limitation of the physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. 95% CIs was calculated with the use of the Clopper-Pearson method.

  2. Percentage of Participants With Drop in LVEF of at Least 10 Points From Baseline and to Below 50% During the Adjuvant Treatment Period at Primary Completion Date (03 March 2016) [ Time Frame: Cycle 9 to Cycle 21 (cycle length=3 weeks; up to approximately 8 months) up to clinical cut-off date, 03 March 2016 (Month 20) ]
    A confirmed event was defined as at least two consecutive readings of declines in LVEF. 95% CIs was calculated with the use of the Clopper-Pearson method.

  3. Percentage of Participants With NYHA Class III and IV Heart Failure at the End of Study [ Time Frame: Baseline up to approximately 6.5 years ]
    LVSD is defined as heart failure. NYHA classifies participants' heart failure condition based on the participant's symptoms. Class III: marked limitation of the physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. 95% CIs will be calculated with the use of the Clopper-Pearson method.

  4. Percentage of Participants With Drop in LVEF of at Least 10 Points From Baseline and to Below 50% at End of Study [ Time Frame: Baseline up to approximately 6.5 years ]
    A confirmed event was defined as at least two consecutive readings of declines in LVEF. 95% CIs will be calculated with the use of the Clopper-Pearson method.

  5. Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Pertuzumab [ Time Frame: Screening then prior to pertuzumab infusion (Hour 0) in Cycles 5, 14, 18 thereafter anytime between Cycle 8 Day 21 and surgery, up to treatment completion visit (cycle length=2-3 weeks; up to approximately 6.5 years) ]
  6. Percentage of Participants With Total Pathological Complete Response (tpCR) Evaluated at the Time of Surgery Based on Local Pathologist's Assessment After Surgery [ Time Frame: 24 weeks after neoadjuvant therapy (Post 8 cycles of neo-adjuvant therapy [cycle length=2¬3 weeks]) ]
    tpCR is defined as the absence of any residual invasive cancer in the breast and the absence of any metastatic cells in the regional lymph nodes.

  7. Percentage of Participants With Clinical Response as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 During the Neoadjuvant Treatment Period [ Time Frame: Baseline until disease progression or death due to any cause up to 24 weeks (assessed on Day 1 of Cycles 1-8 [cycle length=2-3 weeks]) ]
    Clinical response was classified as either complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD: neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. PD: at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions. 95% CIs are calculated with the use of the Clopper-Pearson method.

  8. Event-Free Survival Determined by the Investigator According to RECIST v1.1 [ Time Frame: Baseline until disease progression or death due to any cause up to approximately 6.5 years (assessed on Day 1 of Cycles 1-8 [cycle length=2-3 weeks] and every 3 months thereafter until study completion or early termination) ]
    EFS is defined as the time from enrollment to the first occurrence of progressive disease, relapse, or death from any cause. PD: at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions.

  9. Invasive Disease Free Survival (iDFS) Determined by the Investigator According to RECIST v1.1 [ Time Frame: Baseline until disease progression or death due to any cause up to approximately 6.5 years (assessed on Day 1 of Cycles 1-8 [cycle length=2-3 weeks] and every 3 months thereafter until study completion or early termination) ]
    iDFS is defined as the time from the first date of no disease (the date of surgery) to the first documentation of progressive invasive disease, relapse, or death. PD: at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions.

  10. Overall Survival (OS) [ Time Frame: Baseline up to death (approximately 6.5 years) ]
    OS was defined as the time from enrollment to death from any cause.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female participants with locally advanced, inflammatory, or early-stage, unilateral, and histologically confirmed invasive breast cancer. Participants with inflammatory breast cancer must be able to have a core needle biopsy
  • Primary tumor greater than (>) 2 centimeters (cm) in diameter, or > 5 millimeters (mm) in diameter and node-positive
  • HER2-positive breast cancer confirmed by a central laboratory
  • Availability of tumor tissue specimen
  • Baseline LVEF greater than or equal to (>/=) 55%
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 1
  • At least 4 weeks since major unrelated surgery, with full recovery
  • Women of childbearing potential and male participants with partners of childbearing potential must agree to use a "highly effective" non-hormonal form of contraception or two "effective" forms of non-hormonal contraception by the patient and/or partner. Contraception must continue for the duration of study treatment and for at least 7 months after the last dose of study treatment

Exclusion Criteria:

  • Metastatic disease (Stage IV) or bilateral breast cancer
  • Participants who have had an incisional biopsy of the primary tumor or the primary tumor excised
  • Prior breast or non-breast malignancy within 5 years prior to study entry, except for carcinoma in situ and basal cell and squamous cell carcinoma of the skin. Participants with malignancies occurring more than 5 years prior to study entry are permitted if curatively treated
  • Any previous systemic therapy (including chemotherapy, immunotherapy, HER2 targeted agents, and antitumor vaccines) for cancer, or radiation therapy for cancer
  • Participants with a past history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) are not allowed to enter the study if they have received any systemic therapy for its treatment or radiation therapy to the ipsilateral breast (they are allowed to enter the study if treated with surgery alone)
  • High-risk participants who have received chemopreventive drugs in the past are not allowed to enter the study
  • Inadequate bone marrow, renal, or liver function
  • History or evidence of cardiovascular condition
  • Dyspnea at rest or other diseases that require continuous oxygen therapy
  • Severe, uncontrolled systemic disease
  • Participants with poorly controlled diabetes or with evidence of clinically significant diabetic vascular complications
  • Pregnancy or breast-feeding women
  • Participants who received any investigational treatment within 4 weeks of study start
  • Participants with known infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
  • Current chronic daily treatment with corticosteroids (dose >10 mg methylprednisolone or equivalent [excluding inhaled steroids])
  • Known hypersensitivity to any of the study drugs or excipients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02132949


Locations
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United States, Alabama
University of South Alabama; Mitchell Cancer Institute
Mobile, Alabama, United States, 36604
United States, California
Marin Specialty Care
Greenbrae, California, United States, 94904
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, District of Columbia
MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
Washington, District of Columbia, United States, 20007
Washington Cancer Institute at MedStar Washington Hospital Center.
Washington, District of Columbia, United States, 20010
United States, Florida
Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)
Jacksonville, Florida, United States, 32256
United States, Georgia
Northwest Georgia Oncology Centers PC - Marietta
Marietta, Georgia, United States, 30060
United States, Massachusetts
Berkshire Medical Center
Pittsfield, Massachusetts, United States, 01201
United States, Minnesota
Allina Health, Virginia Piper Cancer Institute
Minneapolis, Minnesota, United States, 55407
United States, Missouri
Saint Lukes Hospital Cancer Institute
Kansas City, Missouri, United States, 64111
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Regional Cancer Care Associates LLC - Morristown
Morristown, New Jersey, United States, 07962
United States, New Mexico
San Juan Oncology Associates
Farmington, New Mexico, United States, 87401
United States, New York
MSKCC @ Commack
Commack, New York, United States, 11725
MSKCC @ West Harrison
Harrison, New York, United States, 10604
Mount Sinai Beth Israel Comprehensive Cancer Center
New York, New York, United States, 10011
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
MSKC @ Rockville
Rockville Centre, New York, United States, 11570
United States, Oklahoma
Mercy Clinic Oklahoma Communties, Inc
Oklahoma City, Oklahoma, United States, 73120
United States, Texas
Harrington Cancer Center
Amarillo, Texas, United States, 79106
United States, Utah
University of Utah; Huntsman Cancer Hospital
Salt Lake City, Utah, United States, 84112
United States, Virginia
Blue Ridge Cancer Care
Roanoke, Virginia, United States, 24014
United States, Washington
PeaceHealth St. Joseph Cancer Center
Bellingham, Washington, United States, 98225
Northwest Medical Specialties
Tacoma, Washington, United States, 98405
Canada, New Brunswick
Horizon Health Network
Moncton, New Brunswick, Canada, E1C 6Z8
Canada, Ontario
Royal Victoria Hospital
Barrie, Ontario, Canada, L4M 6M2
Canada, Quebec
Cite de La Sante de Laval; Hemato-Oncologie
Laval, Quebec, Canada, H7M 3L9
McGill University; St. Mary's Hospital; Oncology
Montreal, Quebec, Canada, H3T 1M5
Hopital Sacre-Coeur Research Centre
Montreal, Quebec, Canada, H4J 1C5
Canada, Saskatchewan
Allan Blair Cancer Centre
Regina, Saskatchewan, Canada, S4T 7T1
Denmark
Herlev Hospital; Afdeling for Kræftbehandling
Herlev, Denmark, 2730
Rigshospitalet; Onkologisk Klinik
København Ø, Denmark, 2100
Vejle Sygehus; Onkologisk Afdeling
Vejle, Denmark, 7100
France
Clinique Victor Hugo; Chimiotherapie
Le Mans, France, 72015
Centre Oscar Lambret; Cancerologie Gynecologique
Lille, France, 59020
Centre Leon Berard; Departement Oncologie Medicale
Lyon, France, 69373
Clinique Clementville; Hopital De Jour
Montpellier, France, 34070
Centre D'Oncologie de Gentilly; Oncology
Nancy, France, 54100
Centre Antoine Lacassagne; Hopital De Jour A2
Nice, France, 06189
Institut Curie; Oncologie Medicale
Paris, France, 75231
Centre Eugene Marquis; Unite Huguenin
Rennes, France, 35042
Institut Gustave Roussy; Departement Oncologie Medicale
Villejuif, France, 94805
Germany
Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe
Dresden, Germany, 01307
Dres.Andreas Ammon und Dirk Meyer
Göttingen, Germany, 37073
Dres. Andreas Köhler und Roswitha Fuchs
Langen, Germany, 63225
Klinikum rechts der Isar der TU München; Klinik und Poliklinik für Frauenheilkunde
München, Germany, 81675
Ruppiner Kliniken, Klinik fuer Gynaekologie und Geburtshilfe
Neuruppin, Germany, 16816
Italy
Policlinico Umberto i di Roma; dip. Scienze Radiologiche, Oncologiche, Anatomopatologiche
Roma, Lazio, Italy, 00161
A.O. Città della Salute e della Scienza - Presidio Molinette; divisione oncologia medica
Torino, Piemonte, Italy, 10126
Asl Le-Ospedale "Vito Fazzi";U.O. Oncologia
Lecce, Puglia, Italy, 73100
Casa Di Cura Di Alta Specialita La Maddalena; Dept. Oncologico Di Iii Livello
Palermo, Sicilia, Italy, 90146
Ospedale Santa Maria Annunziata; Oncologia
Bagno a Ripoli, Toscana, Italy, 50012
Ospedale Della Misericordia; U.O. Di Medicina Ia - Oncologia Medica
Grosseto, Toscana, Italy, 58100
Mexico
Iem-Fucam
D.f., Mexico, 04980
Centro de Diagnóstico y Tratamiento Integral de Mama, Hospital San José Tec de Monterrey
Monterrey, Mexico, 64710
Norway
Haukeland Universitetssjukehus; Klinisk forskningspost
Bergen, Norway, 5021
Oslo universitetssykehus HF, Ullevål, Kreftsenteret
Oslo, Norway, 0450
Poland
Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej
Bialystok, Poland, 15-027
Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii
Kraków, Poland, 30-688
Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii
Otwock, Poland, 05-400
Wielkopolskie Centrum Onkologii; im. Marii Skłodowskiej-Curie
Poznan, Poland, 61-866
Portugal
Centro Clinico Champalimaud; Oncologia Medica
Lisboa, Portugal, 1400-038
Hospital de Santa Maria; Servico de Oncologia Medica
Lisboa, Portugal, 1649-035
Hospital Beatriz Angelo; Departamento de Oncologia
Loures, Portugal, 2674-514
IPO do Porto; Servico de Oncologia Medica
Porto, Portugal, 4200-072
Spain
Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
Badalona, Barcelona, Spain, 08916
Hospital Universitario Reina Sofia; Servicio de Oncologia
Córdoba, Cordoba, Spain, 14004
Centro Oncológico Gallego José Antonio Quiroga y Piñeiro, Servicio de Oncologia
La Coruña, Spain, 15009
Hospital Universitario de la Princesa; Servicio de Oncologia
Madrid, Spain, 28006
Hospital Ramon y Cajal; Servicio de Oncologia
Madrid, Spain, 28034
Hospital Universitario Virgen Macarena; Servicio de Oncologia
Sevilla, Spain, 41009
Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Oncologia
Toledo, Spain, 45004
United Kingdom
Royal United Hospital; Oncology Department
Bath, United Kingdom, BA1 3NG
Royal Bournemouth Hospital; Oncology
Bournemouth, United Kingdom, BH7 7DW
Guys & St Thomas Hospital; Department of Oncology
London, United Kingdom, SE1 9RT
Royal Marsden Hospital - Fulham; Oncology Department
London, United Kingdom, SW3 6JJ
Freeman Hospital; Northern Centre For Cancer Care
New Castle Upon Tyne, United Kingdom, NE7 7DN
Churchill Hospital; Oxford Cancer and Haematology Centre
Oxford, United Kingdom, OX3 7LJ
Peterborough City Hospital, Edith Cavell Campus; Oncology Department
Peterborough, United Kingdom, PE3 9GZ
Royal Marsden Hospital; Dept of Medical Oncology
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02132949    
Other Study ID Numbers: WO29217
2014-000156-28 ( EudraCT Number )
First Posted: May 7, 2014    Key Record Dates
Results First Posted: April 13, 2017
Last Update Posted: January 22, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pertuzumab
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Docetaxel
Albumin-Bound Paclitaxel
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Trastuzumab
Fluorouracil
Epirubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors