General Information

Eloxatin (oxaliplatin) is a platinum-based drug.

Eloxatin is specifically indicated for use in combination with infusional fluorouracil and leucovorin, for:

• adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor
• treatment of advanced colorectal cancer

Eloxatin is supplied as a solution for intravenous infusion. Administer Eloxatin 85 mg/m2 as an intravenous infusion over 120 minutes concurrently with leucovorin over 120 minutes in separate bags, followed by fluorouracil on Day 1 of each 14-day cycle. Administer fluorouracil and leucovorin on Day 2 as recommended. 

• Adjuvant Treatment: Continue treatment for up to 12 cycles or unacceptable toxicity.
• Advanced Colorectal Cancer: Continue treatment until disease progression or unacceptable toxicity. 

Mechanism of Action

Eloxatin (oxaliplatin) is an organoplatinum alkylating agent that increases the tumor response rate to 5-FU/LV treatment. In vivo studies have shown antitumor activity of oxaliplatin against colon carcinoma. In combination with fluorouracil, oxaliplatin exhibits in vitro and in vivo antiproliferative activity greater than either compound alone in several tumor models.

Side Effects

Adverse events associated with the use of Eloxatin in combination with 5-FU/LV may include (but are not limited to) the following:

• Peripheral neuropathy
• Fatigue
• Diarrhea
• Nausea
• Vomiting
• Anemia
• Leukopenia
• Neutropenia
• Thrombocytopenia

The Eloxatin drug label comes with the following Black Box Warning: Eloxatin may also cause anaphylactic-like reactions, which are usually treatable with epinephrine, corticosteroids, and antihistamines. In addition, Eloxatin is linked to pulmonary toxicity which can be fatal.

Clinical Trial Results

Adjuvant Treatment with Eloxatin in Combination with Fluorouracil and Leucovorin

The efficacy of Eloxatin in combination with fluorouracil (FU)/leucovorin (LV) was evaluated in an international, multicenter, randomized trial (MOSAIC] in patients with stage II (Dukes' B2) or III (Dukes' C) colon cancer who had undergone complete resection of the primary tumor. Patients were randomized to receive Eloxatin with fluorouracil/leucovorin or fluorouracil/leucovorin alone for a total of 6 months (i.e., 12 cycles). There were 2246 patients enrolled, of whom 1347 (60%) had Stage III disease. The median duration of follow-up was approximately 77 months. In the overall and the stage III colon cancer populations, DFS was statistically significantly improved in the Eloxatin-containing arm compared to fluorouracil/leucovorin alone; however, a statistically significant improvement in DFS was not observed in Stage II patients. No significant differences in overall survival (OS) were detected in the overall population or those with Stage III disease.

Previously Untreated Advanced Colorectal Cancer

The efficacy of Eloxatin in combination with fluorouracil (FU)/leucovorin (LV) was evaluated in a North American, multicenter, open-label, randomized, active-controlled trial. The trial included 7 arms at different times during its conduct, four of which were closed due to either changes in the standard of care, toxicity, or simplification. During the trial, the control arm was changed to irinotecan with fluorouracil/leucovorin. The main efficacy outcome measure was 3-year disease-free survival (DFS) and additional efficacy outcome measures were overall survival (OS). Patients who received Eloxatin with fluorouracil/leucovorin had a significantly longer time to tumor progression based on investigator assessment, longer OS, and a significantly higher confirmed response rate based on investigator assessment compared to patients who received irinotecan with fluorouracil/leucovorin. 

Previously Treated Advanced Colorectal Cancer

The efficacy of Eloxatin in combination with fluorouracil (FU)/leucovorin (LV) was evaluated in a multicenter, open-label, randomized, three-arm controlled trial was conducted in the US and Canada in patients with advanced colorectal cancer who had relapsed/progressed during or within 6 months of first-line treatment with bolus fluorouracil/leucovorin and irinotecan. Patients were randomized to one of three regimens. The main efficacy outcome measure was 3-year disease-free survival (DFS) and an additional outcome measure was overall survival (OS). Patients treated with the combination of Eloxatin and fluorouracil/leucovorin had an increased response rate compared to patients given fluorouracil/leucovorin or oxaliplatin alone. At the time of the interim analysis 49% of the radiographic progression events had occurred. In this interim analysis an estimated 2-month increase in median time to radiographic progression was observed compared to fluorouracil/leucovorin alone.