Eloxatin Approved as First-Line Treatment of Metastatic Colorectal Cancer

ROCKVILLE, Maryland— Eloxatin (oxaliplatin, Sanofi-Synthelabo) has won marketing approval [Jan. 2004] from the Food and Drug Administration (FDA) for the first-line treatment of metastatic colorectal cancer in combination with fluorouracil(Drug information on fluorouracil) and leucovorin (5-FU/LV), commonly called FOLFOX. The agency approved the company's Supplemental New Drug Application based on the results of a study sponsored by the National Cancer Institute. That study found that advanced colorectal cancer patients treated with the drug regimen had statistically significant improvements in median survival- 4.8 months-tumor response, and time to progression, compared with those treated with irinotecan(Drug information on irinotecan) (Camptosar) plus bolus 5-FU/LV. "The finding that the oxaliplatin(Drug information on oxaliplatin)based regimen demonstrated a longer survival time for patients is a major step forward," said Richard M. Goldberg, MD, University of North Carolina. "This is the greatest increase in survival time we have seen in a chemotherapy regimen used in advanced colorectal cancer." Dr. Goldberg served as the study chair for the trial that Sanofi-Synthelabo submitted in support of its FDA application. N9741
The study on which the FDA based its approval was designated N9741 and supervised by the North Central Cancer Treatment Group. It randomized patients to the FOLFOX regimen or to receive irinotecan plus 5-FU/LV (IFL). Patients in the FOLFOX arm had a median survival of 19.4 months after treatment initiation vs 14.6 months for those in the IFL group-a 38% survival advantage. The FOLFOX group also had a significantly higher overall tumor response rate in patients with measurable disease, 45% vs 33%, as well as a significantly longer time to disease progression, 8.7 months vs 6.9 months. The commonly reported side ef- fects with FOLFOX included neutropenia and paresthesia. However, studies and clinical experience have shown an association of Eloxatin with potentially fatal pulmonary toxicity, and anaphylactic-like reactions that may occur minutes after drug administration. These reactions have been treated with epinephrine(Drug information on epinephrine), corticosteroids, and antihistamines. Two kinds of primarily peripheral sensory neuropathy have been seen with Eloxatin-an acute, reversible type and a persistent form. The drug's labeling section carries a black box warning that states: "Eloxatin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available." Eloxatin is approved in more than 60 countries for the first- and/or second- line treatment of metastatic colorectal cancer, according to Paris-based Sanofi-Synthelabo, which said worldwide sales of the drug in 2003 would exceed $1 billion.