On January 9, 2004, the FDA approved oxaliplatin for injection (Eloxatin™, a trademark of Sanofi-Synthelabo Inc.), for use in combination with infusional 5-fluorouracil (5-FU) and leucovorin (LV) for the initial treatment of advanced colorectal cancer.

Eloxatin previously received accelerated approval on August 9, 2002, for use in combination with infusional 5-FU/LV for the treatment of patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed during or within six months of completion of first-line therapy with the combination of bolus 5-FU/LV and irinotecan.

Safety and efficacy were demonstrated in one multicenter, randomized controlled clinical trial sponsored by the National Cancer Institute as an inter-group study led by the North Central Cancer Treatment Group. The study had seven arms at different times during its conduct, four of which were closed either due to changes in the standard of care, toxicity, or simplification.

During the study, the control arm was changed to irinotecan plus bolus 5-FU/LV. The Eloxatin + infusional FU/LV regimen was compared to an approved control regimen of irinotecan plus bolus 5-FU/LV in 531 concurrently randomized patients previously untreated for locally advanced or metastatic colorectal cancer. Patients may have received adjuvant therapy for resected stage II or III disease without recurrence within 12 months. After completion of enrollment, the dose of irinotecan plus 5-FU/LV was decreased due to toxicity.

The Eloxatin + infusional FU/LV regimen showed superior survival to the irinotecan plus bolus FU/LV regimen with median survivals of 19.4 and 14.6 months (p=0.0001), respectively. Time to tumor progression and tumor response rate were also superior on the Eloxatin + infusional FU/LV regimen.

Fatigue, neuropathy, nausea, vomiting, diarrhea, stomatitis, neutropenia, and thrombocytopenia were the more common adverse events. Febrile neutropenia or requirement for platelet transfusion were not increased as compared to the irinotecan + bolus 5-FU/LV.

Eloxatin has been associated with pulmonary fibrosis (<1 percent of study patients), which may be fatal. There have been reports while on study and from post-marketing surveillance of prolonged prothrombin time and INR occasionally associated with hemorrhage in patients who received Eloxatin plus 5-FU/LV while on anticoagulants. Patients requiring oral anticoagulants may require closer monitoring.

Hypersensitivity has been observed (<2 percent Grade ¾) in clinical studies and was usually managed with standard epinephrine, corticosteroid, antihistamine therapy, and may require discontinuation of therapy.

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

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