Duloxetine does not appear to prevent chemotherapy-related neuropathy in colorectal cancer treatment
The antidepressant duloxetine does not appear to prevent chemotherapy-associated nerve damage in colorectal cancer. This finding appeared in the JCO Oncology Advances on March 25, 2026 followed by a press release on April, 8, 2026.
As background, the authors noted that oxaliplatin is a standard chemotherapy drug used to treat colorectal cancer. However, a common and sometimes permanent side effect of oxaliplatin treatment is the onset of peripheral neuropathy, causing numbness, tingling, and pain in the hands and feet.
Duloxetine is often prescribed off-label for the treatment of established painful chemotherapy-induced peripheral neuropathy.
“Since we know duloxetine is effective at treating painful neuropathy caused by neurotoxic chemotherapy drugs, we wanted to see if the medication could also prevent the side effect from developing in the first place,” said Ellen M. Lavoie Smith, PhD, MSN, Interim Associate Dean of Research and Scholarship at the University of Alabama at Birmingham School of Nursing and chair for the study “The results show that duloxetine is not more effective than a placebo at preventing neuropathy caused by chemotherapy in patients with colorectal cancer.”
The investigators randomized 199 subjects 1:1:1 to receive once daily 30 mg duloxetine, 60 mg duloxetine or placebo. Eligible subjects had been diagnosed with stage II to III colorectal cancer and had no baseline neuropathy. They were at least 25 years-old.
The subjects received oxaliplatin at one of the following doses and on one of the following schedules: 85 mg/m2 every 2 weeks (6 or 12 doses) or 130 mg/m2 every 3 weeks (4 doses).
They received duloxetine or placebo once-daily beginning on day 1 of cycle 1 and continued for 17 weeks.
The primary endpoint was a patient reported composite measure of neuropathy severity and onset, assessed several weeks after completion of chemotherapy.
The authors reported that the trial results revealed no statistically or clinically meaningful difference between either duloxetine or placebo in preventing neuropathy.
“While duloxetine remains an important option for managing painful chemotherapy induced neuropathy once it develops, this trial confirms that it should not be used for prevention,” Dr. Smith said.
The trial was conducted by the Alliance for Clinical Trials in Oncology with support from the National Cancer Institute (USA).
