Oxaliplatin-Based Combination Treatment Confirmed Effective in Colorectal Cancer That Has Progressed
Key Words
Colorectal cancer, FOLFOX, oxaliplatin. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
The chemotherapy regimen known as FOLFOX – oxaliplatin plus fluorouracil (5-FU) plus leucovorin – produced higher response rates and a significant delay in tumor progression in patients with metastatic colorectal cancer, compared to other therapy.
Source
American Society of Clinical Oncology (ASCO) annual meeting, Chicago, June 1, 2003. The data were also published in the June 1, 2003, issue of the Journal of Clinical Oncology; see the journal abstract.
Background
Early results from this trial – called EFC 4584 – led to U.S. Food and Drug Administration (FDA) approval of oxaliplatin as a treatment for patients with advanced colorectal cancer that had progressed after chemotherapy (second-line therapy). These final results substantiate the earlier data and provide more details than have been available up to now, including survival data.
(A separate trial also presented at the 2003 ASCO confirms earlier data on the superiority of the FOLFOX regimen as initial – “first line” – therapy for advanced colorectal cancer. Mature data from the N9741 trial, an intergroup trial led by the North Central Cancer Treatment Group, showed conclusively that FOLFOX was more effective than two other combinations in these patients, increasing both response rate and survival, while lowering toxicity. The North Central Cancer Treatment Group is an NCI-sponsored clinical trials cooperative group. N9741 was sponsored by NCI in partnership with the maker of oxaliplatin, Sanofi-Synthelabo.)
The Study
The 821 patients in the multicenter EFC 4584 trial, led by Mace L. Rothenberg, M.D., at the Vanderbilt-Ingram Cancer Center, Nashville, Tenn., had metastatic colorectal cancer that had first been treated with the standard therapy of irinotecan, 5-FU, and leucovorin, known as IFL (also known as the Saltz regimen). They were randomly divided into three groups; one group received 5-FU and leucovorin, one received oxaliplatin alone, and one received the FOLFOX combination.
Results
About 9 percent of patients responded to the FOLFOX regimen compared to about 1 percent for the other two regimens. The delay in tumor progression was 4.9 months for patients receiving FOLFOX and 2.6 months for those receiving 5-FU and leucovorin. Oxaliplatin as a single agent produced results comparable to 5-FU and leucovorin. These results “were highly statistically significant,” said Rothenberg.
Substantial side effects were more frequent among patients receiving FOLFOX. These patients were more likely to experience nausea, diarrhea, neuropathy, and low white blood cell and platelet counts compared to those who received either of the other two therapies.
Nonetheless, concluded the investigators, these results mean that FOLFOX offers a useful “second line” therapy option to patients whose treatment with IFL fails to stop the disease.
Limitations
Although the response rates and time to tumor progression were superior for FOLFOX as a second-line therapy, the trial was not able to demonstrate an overall survival advantage for the regimen.
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