Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity Caused By Oxaliplatin in Patients Receiving Combination Chemotherapy for Stage II, Stage III, or Stage IV Colorectal Cancer That Has Been Completely Removed By Surgery

• Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event [ Time Frame: 127 days ] [ Designated as safety issue: Yes ]
  Neuropathic adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Neurotoxicity evaluation grade: loss of deep tendon reflexes or paresthesia, including tingling, but not interfering with function (Grade 1); objective sensory alteration or paresthesia, including tingling, interfering with function, but not with activities of daily living (Grade 2); sensory alteration or paresthesia interfering with activities of daily living (Grade 3); permanent sensory losses that are disabling (Grade 4)
  
  

• Time to Onset of Grade 2+ Chronic Neurotoxicity [ Time Frame: 127 days ] [ Designated as safety issue: No ]
  Neurotoxicity were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0.
  
  
• Time to Onset of Grade 3+ Chronic Neurotoxicity [ Time Frame: 127 days ] [ Designated as safety issue: Yes ]
  Neurotoxicity was assessed by CTCAE v3.0.
  
  
• Average Duration of Chronic Neuropathic Toxicity [ Time Frame: 127 days ] [ Designated as safety issue: No ]
  Neuropathic adverse events were assessed by CTCAE v3.0.
  
  
• Percentage of Patients Discontinuing Therapy for Chronic Neurotoxicity [ Time Frame: 127 days ] [ Designated as safety issue: No ]
  Neurotoxicity were assessed by CTCAE v3.0.
  
  
• Average Cumulative Oxaliplatin Dose [ Time Frame: 127 days ] [ Designated as safety issue: No ]
  
• Average Duration of Oxaliplatin-containing Treatment [ Time Frame: 127 days ] [ Designated as safety issue: No ]
  
• Percentage of Patients With Acute Neuropathic Adverse Event [ Time Frame: 127 days ] [ Designated as safety issue: Yes ]
  Acute neuropathic toxicities were measured using the Symptom Experience Diary and supplemental quality of life questions in the scale of 0 (no symptom) to 10 (worst symptom). The item score was reversed and transformed into 0 (low QOL) to 100 (best QOL) scale for analysis. Any score greater than 0 was considered having acute neuropathy.
  
  
• Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event [ Time Frame: 127 days ] [ Designated as safety issue: Yes ]
  Adverse Events were measured using CTCAE V3.0.
  
  
• Percentage of Patients Experiencing Impact on Activities of Daily Living (ADL) [ Time Frame: 127 days ] [ Designated as safety issue: No ]
  Activities of daily living were measured using the Symptom Experience Diary and supplemental quality of life questions. The questionnaires' items were in the scale of 0 (no symptom) to 10 (worst symptom).
  
  
• Change From Baseline in Fatigue Score at One Month [ Time Frame: Baseline and One month ] [ Designated as safety issue: No ]
  Fatigue was measured by Brief Fatigue Inventory in the scale of 0 (no fatigue) to 10 (fatigue as bad as you can imagine). The item score was reversed and transformed into 0 (low quality of life (QOL)) to 100 (best QOL) scale for analysis. Change: score at one month minus score at baseline.
  
  
• Change From Baseline in Quality of Life (QOL) at One Month [ Time Frame: Baseline and One month ] [ Designated as safety issue: No ]
  Quality of Life (QOL) were measured using the Symptom Experience Diary and supplemental quality of life questions. Item score range: 0 (no symptom) to 10 (worst symptom). The score was reversed and transformed into 0 (low QOL) to 100 (best QOL) scale for analysis. Change: score at one month minus score at baseline.
  
  

OBJECTIVES:

• Determine whether calcium gluconate and magnesium sulfate (CaMg) infusions can prevent or ameliorate chronic, cumulative oxaliplatin-induced neurotoxicity in patients receiving FOLFOX combination chemotherapy for stage II, III or IV colorectal cancer.
• Determine whether CaMg infusions can increase the cumulative oxaliplatin doses that can be delivered without chronic neurotoxicity.
• Determine whether CaMg infusions can ameliorate the acute neuropathy associated with oxaliplatin.
• Determine whether CaMg infusions cause any adverse events.
• Investigate whether CaMg infusions influence quality of life, fatigue, and activities of daily living of these patients.
• Determine if polymorphisms in the GSTP1 gene predict early onset of oxaliplatin-induced neurotoxicity.

OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to age (< 65 vs > 65), gender, and chemotherapy regimen (FOLFOX4 vs modified FOLFOX6). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after each oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen.
• Arm II: Patients receive a placebo IV over 30 minutes immediately before and after each oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen.

In both arms, treatment continues until chemotherapy is discontinued (approximately 6 months).

Patients complete quality of life questionnaires on day 1, a symptom experience diary on days 2-5 of their chemotherapy regimen, and questionnaires at 1 and 3 months after completion of study treatment.

Blood samples are collected at baseline and tested for the GSTP1 gene.

After completion of study treatment, patients are followed for at least 3 months.

PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.