A randomized trial conducted by the Oncology Clinical Trials Alliance with support from the National Cancer Institute found that duloxetine, a drug commonly used to treat chronic pain and mental illness, did not prevent nerve damage caused by chemotherapy in colorectal cancer patients. The primary analysis of Alliance A221805 is JCO Advances in Oncology.
Oxaliplatin is a standard chemotherapy drug used to treat colorectal cancer, but it can often cause peripheral neuropathy and can have permanent side effects that cause numbness, tingling, and pain in the hands and feet. Duloxetine is often prescribed for chronic painful conditions such as osteoarthritis and diabetic neuropathy, as well as many psychological conditions (e.g., anxiety, depression), and is already recommended for the treatment of established painful chemotherapy-induced peripheral neuropathy.
Because we know that duloxetine is effective in treating painful neuropathy caused by neurotoxic chemotherapy drugs, we wanted to see if the drug could also prevent side effects from occurring in the first place. The results indicate that duloxetine is no more effective than placebo in preventing chemotherapy-induced neuropathy in colorectal cancer patients. ”
Ellen M. Lavoie Smith, Ph.D., MSN, Interim Associate Dean for Research and Scholarship, University of Alabama at Birmingham School of Nursing, Research Chair, Alliance A221805
The study, led by Dr. Smith, is the largest randomized trial to date specifically designed to evaluate whether duloxetine can prevent oxaliplatin-induced peripheral neuropathy.
This double-blind, placebo-controlled trial enrolled 199 adults with stage II or III colorectal cancer at 73 cancer centers across the United States. Participants had no pre-existing neurological disorders and were randomly assigned to receive the following treatments:
- Duloxetine 30mg per day
- Duloxetine 60 mg per day
- placebo
Treatment started on the first day of oxaliplatin-based chemotherapy and continued for 17 weeks. The primary endpoint was a composite measure of patient-reported neurological deficit severity and onset, assessed several weeks after completion of chemotherapy. Results showed no statistically or clinically meaningful differences between duloxetine doses and placebo.
“While duloxetine remains an important option for managing painful chemotherapy-induced neuropathy when it occurs, this trial confirms that duloxetine should not be used for prophylaxis,” Dr. Smith said.
The findings highlight the unmet need for effective strategies to prevent chemotherapy-induced neurological damage, which can have a significant impact on the long-term quality of life of cancer survivors.
This study was supported by the National Cancer Institute of the National Institutes of Health under awards UG1CA189823, UG1CA189972, R01CA235726, and U10CA180868.
sauce:
Alliance for Clinical Trials in Oncology
Reference magazines:
Lavoie-Smith, E.M. others. (2026). Alliance A221805: Duloxetine to prevent oxaliplatin-induced chemotherapy-induced peripheral neuropathy: a randomized, double-blind, placebo-controlled phase II study. JCO Advances in Oncology. DOI: 10.1200/OA-25-00107. https://ascopubs.org/doi/10.1200/OA-25-00107
