Sanofi-Synthelabo recently announced that its platinum-based drug oxaliplatin (Eloxatin) has been approved by the US Food and Drug Administration (FDA) for use in combination with infusional fluorouracil (5-FU)/leucovorin in advanced colorectal cancer patients whose disease has recurred or progressed after bolus 5-FU/leucovorin plus irinotecan (CPT-11, Camptosar) therapy. The FDA approval is based on the response rate and improved time to tumor progression observed in an ongoing trial. Data that demonstrate a clinical benefit, such as improvement in disease-related symptoms or an increase in survival are not yet available.
Sanofi-Synthelabo recently announced that its platinum-based drug oxaliplatin (Eloxatin) has been approved by the US Food and DrugAdministration (FDA) for use in combination with infusional fluorouracil (5-FU)/leucovorinin advanced colorectal cancer patients whose disease has recurred or progressedafter bolus 5-FU/leucovorin plus irinotecan (CPT-11, Camptosar) therapy. The FDAapproval is based on the response rate and improved time to tumor progressionobserved in an ongoing trial. Data that demonstrate a clinical benefit, such asimprovement in disease-related symptoms or an increase in survival are not yetavailable.
In the pivotal investigation, oxaliplatin in combination withinfusional 5-FU/leucovorin demonstrated a statistically significant responserate compared with infusional 5-FU/leucovorin alone. Additionally, interim datafrom the investigation on the median time to disease progression showed anincrease of 2 months with the oxaliplatin combination, compared toinfusional 5-FU/leucovorin alone.
"Eloxatin in combination with infusional 5-FU/leucovorinprovides an alternative for patients who previously had only limitedoptions," said Mace Rothenberg, md, lead investigator for the trial andIngram Associate Professor of Cancer Research at the Vanderbilt-Ingram CancerCenter, Vanderbilt University, Nashville, Tennessee. In addition, he noted,"oxaliplatin is being evaluated for its impact on disease-related symptomsincluding pain, weight loss, fatigue, and its effect on survival."
Dan Haller, md, professor of medicine at the University ofPennsylvania Cancer Center, and who directs other clinical studies withoxaliplatin, said, "Eloxatin in combination with infusional 5-FU/leucovorinadds a new weapon to what has been a very small arsenal of effective treatmentsfor advanced colorectal cancer. In patients whose advanced colorectal cancer hasrecurred or progressed, meaningful options have been few." He added,"The approval of Eloxatin may change the way we treat our patients."
Clinical Trial Results
The New Drug Application for oxaliplatin was based on theresults of a US-Canadian multicenter, randomized, controlled investigation. Thisstudy compared the safety and efficacy of oxaliplatin plus infusional 5-FU/leucovorinwith that of infusional 5-FU/leucovorin alone and oxaliplatin alone.
The trial included 463 patients with advanced colorectalcancer whose disease had relapsed or progressed either during or within6 months of therapy with bolus 5-FU/leucovorin plus irinotecan. Accrual tothis study is completed, with 821 patients enrolled. Survival will be assessedin all patients enrolled in the study. Tumor response was assessed every threecycles (6 weeks) using the standard Response Eval-
uation Criteria in Solid Tumors
The confirmed rate of objective tumor responsedefined as a30% or greater reduction in overall tumor size, maintained for 4 weeks or morewas9% for patients receiving oxaliplatin plus infusional 5-FU/leucovorin (n = 152),compared with 0% for those given infusional 5-FU/leucovorin alone (n = 151, P= .0002) and 1% for those on oxaliplatin alone (n = 156).
The median time to tumor progression for oxaliplatin incombination with infusional 5-FU/leucovorin was 4.6 months, compared with 2.7for infusional 5-FU/leucovorin alone and 1.6 months for oxaliplatin alone. Thisrepresents a 2-month increase in median time to progression compared toinfusional 5-FU/leucovorin alone.
The most frequently reported adverse events with oxaliplatin in combinationwith infusional 5-FU/leucovorin are peripheral neurosensory events (74% overall,56% acute, and 48% persistent), fatigue (68%), diarrhea (67%), nausea (65%), andvomiting (40%). Changes in hematology parameters were also seen: anemia (81%),leukopenia (76%), neutropenia (73%), and thrombocytopenia (64%).