• Time to onset of grade 2+ chronic neurotoxicity as assessed by CTCAE v3.0 [ Designated as safety issue: No ]
• Time to onset of grade 3+ chronic neurotoxicity as assessed by CTCAE v3.0 [ Designated as safety issue: No ]
• Average duration of chronic neuropathic toxicity as assessed by CTCAE v3.0 [ Designated as safety issue: No ]
• Percentage of patients discontinuing therapy as assessed by CTCAE v3.0 [ Designated as safety issue: No ]
• Average cumulative oxaliplatin dose [ Designated as safety issue: No ]
• Average duration of treatment [ Designated as safety issue: No ]
• Percentage of patients with acute neuropathic toxicity [ Designated as safety issue: No ]
• Incidence of calcium magnesium (CaMg)-induced toxicity [ Designated as safety issue: Yes ]
• Percentage of patients experiencing impact on activities of daily living (ADL) [ Designated as safety issue: No ]
• Average fatigue from baseline to 1 month [ Designated as safety issue: No ]
• Average quality of life from baseline to 1 month
• Percentage of patients with grade 2+ chronic neuropathic toxicity who express the GSTP1 1105V polymorphism [ Designated as safety issue: No ]
• Time to onset of grade 2+ chronic neuropathic toxicity comparison between patients who either express or don't express the GSTP1 1105V polymorphism [ Designated as safety issue: No ]

• Time to onset of grade 2+ chronic neurotoxicity as assessed by the Kaplan-Meier method
• Time to onset of grade 3+ chronic neurotoxicity as assessed by the Kaplan-Meier method
• Average duration of chronic neuropathic toxicity as assessed by the Kaplan-Meier method
• Percentage of patients discontinuing therapy as assessed by the Chi-square method
• Average cumulative oxaliplatin dose as assessed by the Chi-square method
• Average duration of treatment as assessed by the Kaplan-Meier method
• Percentage of patients with acute neuropathic toxicity as assessed by the Chi-square method
• Incidence of calcium magnesium (CaMg)-induced toxicity as assessed by the Chi-square method and descriptive statistics
• Percentage of patients experiencing impact on activities of daily living (ADL) as assessed by the Chi-square method
• Average fatigue as measured by the 2-sample t-test from baseline to 1 month
• Average quality of life as assessed by the 2-sample t-test from baseline to 1 month
• Percentage of patients with grade 2+ chronic neuropathic toxicity who express the GSTP1 1105V polymorphism as assessed by the Chi-square method
• Time to onset of grade 2+ chronic neuropathic toxicity comparison between patients who either express or don't express the GSTP1 1105V polymorphism as assessed by the Kaplan-Meier method

RATIONALE: Calcium gluconate and magnesium sulfate may prevent or lessen neurotoxicity caused by oxaliplatin. It is not yet known whether calcium gluconate and magnesium sulfate are more effective than a placebo in preventing neurotoxicity caused by oxaliplatin in patients receiving combination chemotherapy.

PURPOSE: This randomized phase III trial is studying calcium gluconate and magnesium sulfate to see how well they work compared to a placebo 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.

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.

• Colorectal Cancer
• Neurotoxicity

• Drug: calcium gluconate
• Drug: magnesium sulfate
• Other: placebo

• Experimental: 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.
• Placebo Comparator: Patients receive a placebo IV over 30 minutes immediately before and after each oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon or rectum

  • Stage II disease
  • Stage III disease
  • Stage IV disease (completed resected with no evidence of residual tumor)
• Must have undergone curative resection for stage II or III disease

• Scheduled to receive 6 months of adjuvant treatment with either of the following FOLFOX chemotherapy regimens:

  • FOLFOX4, comprising leucovorin calcium, fluorouracil, and oxaliplatin (2-week course)
  • Modified FOLFOX6, comprising high-dose leucovorin calcium, high-dose fluorouracil, and oxaliplatin (2-week course)

PATIENT CHARACTERISTICS:

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• WBC ≥ 3,000/mm^3
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Creatinine ≤ 1.5 times ULN
• Calcium normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No pre-existing peripheral neuropathy of any grade
• No hypercalcemia
• No concurrent heart block or a history of heart block
• No other medical condition that, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
• No family history of a genetic/familial neuropathy

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior treatment with neurotoxic chemotherapy such as oxaliplatin, cisplatin, taxanes, or vinca alkaloids
• Concurrent use of bevacizumab or cetuximab in combination with FOLFOX as part of a clinical trial or clinical practice are allowed
• No concurrent digitalis medication
• No concurrent digoxin
• No concurrent treatment with anticonvulsants such as carbamazepine, phenytoin, or valproic acid
• No other concurrent neurotropic agents such as gabapentin