Researchers from Scotland have reported that xaliproden (SR57746A) reduces the risk of grade 3-4 peripheral neuropathy associated with Eloxatin® (oxaliplatin) in patients with colorectal cancer. The details of this randomized study were presented at the June 2006 meeting of the American Society of Clinical Oncology held in Atlanta, Georgia.

Eloxatin is a commonly used chemotherapy drug for the treatment of colorectal cancer. A common side effect associated with Eloxatin is peripheral neuropathy. When peripheral neuropathy becomes severe enough, doses of Eloxatin are reduced. However, a reduction in dose or delay in treatment often results in suboptimal outcomes. Therefore, preventing side effects or reducing their severity is a vital part of optimal treatment delivery and improved long-term outcomes. Furthermore, peripheral neuropathy may become a persistent condition, affecting the quality of life for long-term survivors.

Researchers from Scotland recently conducted a phase III clinical trial to evaluate xaliproden for the prevention of neurological complications of Eloxatin. Xaliproden is a non-peptide compound which has shown to exhibit a wide range of neurotrophic effects, both in vitro and in vivo. Most recently this agent has shown modest effects in amyotropic lateral sclerosis and Alzheimer’s disease.

This trial included 749 patients with metastatic colorectal cancer who were being treated with the chemotherapy combination FOLFOX (5-fluorouracil, Eloxatin, leucovorin). Approximately half of the patients received xaliproden and the other half received placebo.

• Patients who received xaliproden were 39% less likely to have grade 3-4 neuropathy than those who had not received xaliproden.
• Fewer patients who received xaliproden had to discontinue treatment with FOLFOX due of the severity of peripheral neuropathy compared to those who received placebo (14% versus 17%, respectively).
• There were no differences in anticancer response rates between the two groups: nearly 45% for patients treated with xaliproden/FOLFOX and 43% for patients treated with FOLFOX only.
• Rates of diarrhea were increased by nearly 2% for patients receiving xaliproden, and rates of pulmonary embolism increased by approximately 2% for patients receiving xaliproden compared to those treated with chemotherapy only. Neutropenia decreased by nearly 5% in the group of patients who received xaliproden.

These researchers concluded that the addition of xaliproden to treatment including Eloxatin appears to reduce the incidence and severity of peripheral neuropathy. Further trials are necessary to confirm this finding; however, with improved long-term survival, quality of life issues become important to address.

Comments:   These are very important findings and if confirmed could offer a preventative for neurotoxic chemotherapy agents such as Eloxatin.

Reference: Cassidy J, Bjarnason A, Hickish T, et al. Randomized double blind (DB) placebo (plcb) controlled phase III study assessing the efficacy of xaliproden (X) in reducing the cumulative peripheral neuropathy (PSN) induced by oxaliplatin (Ox) and 5-FU/LV combination (FOLFOX4) in 1st line treatment of patients (pts) with metastatic colorectal cancer. Journal of Clinical Oncology . 2006;24:Abstract # 3507.

Related news   

Xaliproden May Reduce Side Effect Caused by Eloxatin® in Colorectal Cancer (02/06/2006)

Addition of Cetuximab (Erbitux®) to FOLFOX4 Appears Promising as First-Line Therapy for Metastatic Colorectal Cancer (5/15/2005)

Addition of High-Dose Avastin™ to FOLFOX4 Improves Survival in Recurrent Colorectal Cancer  (5/15/2005)

Oxaliplatin Combined with 5FU and Lecovorin Approved for Adjuvant Therapy of Stage III Colon Cancer  (11/22/2004)

Adjuvant Eloxatin® and 5-FU-leucovorin Improves Survival of Colorectal Cancer  (6/16/2004)