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Title: High Dropout Rate in Colorectal Cancer Trial Linked to Oxaliplatin-Caused Sensory Neurotoxicity: Presented at ASCO-GI

"High Dropout Rate in Colorectal Cancer Trial Linked to Oxaliplatin-Caused Sensory Neurotoxicity: Presented at ASCO-GI"

By Ed Susman HOLLYWOOD, FL -- January 31, 2005 -- More than 60% of patients with advanced colorectal cancer being treated with oxaliplatin-based therapies dropped out of a clinical trial for reasons other than progressive disease. "We looked at every one of the reports on patients who dropped out of the trial because of reasons other than progressive disease," said Alex Grothey, MD, a Mayo Foundation scholar at the Mayo Clinic, Rochester, Minnesota. Previous results from the Intergroup Trial N9741 helped establish the use of oxaliplatin as part of front-line therapy for patients with advanced colorectal cancer. In their follow-up evaluation of patients in this study, the researchers found that 62.2% of the 696 patients assigned to the FOLFOX4 regimen (5-fluorouracil, leucovorin, and oxaliplatin) discontinued treatment due to adverse effects associated with treatment, Dr. Grothey said during his presentation here January 29[^th at the 2005 Gastrointestinal Cancers Symposium.

While the study showed that FOLFOX4 appeared to provide a survival advantage over an irinotecan, 5-FU, leucovorin regimen (IFL), Dr. Grothey said than 23% of the patients discontinued FOLFOX4 therapy due to sensory neurotoxicity. Overall, 74% of patients in the study who experienced grade 3 sensory neurotoxicity dropped out of the study.

Another 23% discontinued due to myelosuppression, which Dr. Grothey attributed to the administration of 5-FU in a bolus injection.

About 7% of patients reported that hypersensitivity forced them out of the study; 9% of the patients responded well enough that they were able to undergo potentially curative surgery.

"What we saw in this study was that the time to treatment failure -- when patients would discontinue treatment -- occurred at about 5.8 months," he said, "while median time to progression of disease was 9.2 months."

The analysis also showed that the median time to response with FOLFOX4 was 2.2 months; the median time to grade 2 sensory neurotoxicity was 5 months; and the median time to grade 3 sensory neurotoxicity was 6 months. "The vast majority of the patients responded by the time the regimen became too toxic for them to continue," he said.

The N9741 trial was conducted by the North Central Cancer Treatment Group, the Cancer and Leukemia Group B, the Eastern Cooperative Oncology Group, the Southwest Oncology Group, and the National Cancer Institute of Canada Clinical Trials Group.

Dr. Grothey has received honoraria and has acted as a consultant for Sanofi-Aventis, the company which markets oxaliplatin.

Dr. Grothey said further clinical trials would attempt to identify strategies that could reduce the toxicity of the regimen and possibly enhance time to progression.

The symposium was cosponsored by the American Society of Clinical Oncology, the American Gastroenterological Association, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

[Presentation title: Detailed Analysis of Oxaliplatin-Associated Neurotoxicity in Intergroup Trial N9741. Abstract 182]

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