Oxaliplatin extends life in advanced colorectal cancer.
Furthermore, patients who received oxaliplatin along with two standard drugs had a heightened chance of undergoing potentially curative surgery because their tumors had regressed enough to make resection possible.
Dr. Alfredo Falcone, professor of medical oncology at the University of Pisa and chairman of oncology at Livorno Hospital, reported early results of a phase III Italian study at a symposium sponsored by the American Society of Clinical Oncology.
The study enrolled 244 patients with previously untreated, unresectable colorectal cancer. Half the patients received three chemotherapy drugs first line: irinotecan, 5-fluorourcil (5-FU) with leucovorin (LV), and oxaliplatin--the FOLFOXIRI regimen. The other patients received irinotecan plus LV and 5-FU, a regimen called FOLFIRI.
Oxaliplatin was approved by the FDA for first-line treatment of advanced colorectal cancer in late 2004, the first new chemotherapeutic agent for the disease in a decade.
After a median 14 months of follow-up, patients in the FOLFOXIRI arm had a median survival of 22.6 months, compared with 16.7 months for those in the first-line FOLFIRI arm. Complete or partial tumor regression was seen in 66% of FOLFOXIRI patients, compared with 41% of the FOLFIRI group.
Some FOLFOXIRI patients demonstrated substantial tumor regression, enabling 18 (15%) of 122 patients to undergo a curative (R0) liver resection. With the FOLFIRI regimen, 7 (6%) of 122 patients responded that well.
The difference was most pronounced among patients whose metastases were confined to the liver, Dr. Falcone said. Of those, 14 (36%) of 39 patients on FOLFOXIRI and 5 (12%) of 42 patients on FOLFIRI underwent a radical resection that left no evidence of disease. The trial allowed patients to remain on either regimen for 6 months.
At that time, disease was progressing in 18% of patients who received FOLFOXIRI, compared with 45% who received FOLFIRI first-line. (For ethical reasons, oxaliplatin was given to patients in the FOLFIRI arm when disease progression was noted.) Adding oxaliplatin to the standard doublet regimen exacerbated toxicity to patients, but their symptoms were "manageable," Dr. Falcone said.
Grade 3-4 neutropenia and grade 2-3 peripheral neuropathy, as well as diarrhea and vomiting, were seen more often in patients receiving FOLFOXIRI than in those receiving just two drugs.
Dr. Jordan Berlin, clinical director of gastrointestinal oncology at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said he found the Italian study "very intriguing."
"With FOLFOXIRI, you're gaining toxicity," he said at the symposium, also sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology. "I'd [accept] that toxicity if I had a patient with liver metastasis only and I had an increased chance of getting that patient to surgery and possible cure," Dr. Berlin said at a press briefing during the symposium.
"I don't think I'd [accept] it if I had liver, lung, lymph node, and bone metastasis. I'd rather do as much as I could to keep the patient alive and feeling as well as possible," he added. Dr. Berlin said he was pleased that the Italian multicenter Gruppo Oncologico Nord Ovest intended to launch a larger comparative study.
In the United States, six major randomized trials are underway to study other combinations of first-line therapy in advanced colorectal cancer, he said.
BY BETSY BATES
Los Angeles Bureau
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|Publication:||Internal Medicine News|
|Date:||Mar 1, 2006|
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