The antidepressant duloxetine (Cymbalta) appears to reduce painful peripheral neuropathy associated with taxane- or platinumbased chemotherapy in some, but not all, patients, according to a randomized phase 3 study presented at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO). About one-third of patients treated with duloxetine reported at least a 30% or greater reduction in pain scores versus 17% of placebo patients.
“Unfortunately, no medication is completely effective. Duloxetine isn’t perfect and did not work for every patient in our study, but it was effective for a majority of patients. This was the first randomized trial to show that any drug is effective for this terrible pain,” stated lead author Ellen M. Lavoie Smith, PhD, assistant professor in the School of Nursing at the University of Michigan in Ann Arbor.
Painful peripheral neuropathy, which affects 20% to 30% of patients treated with taxane- or platinum-based chemotherapy, can be debilitating, interfering with the ability to perform activities of daily living. Thus far, there is no established effective treatment for this adverse event, which can persist for years after chemotherapy is completed.
The study randomized 231 patients to duloxetine followed by placebo versus placebo followed by duloxetine; 220 patients received the initial treatment with 187 patients completing the initial treatment period. All patients reported high levels of pain from peripheral neuropathy prior to enrollment. Duloxetine was given as one 30-mg oral capsule per day for 1 week, followed by 2 capsules per day (60 mg) for 4 more weeks.
“The gradual dosing was employed to reduce the side effects of duloxetine, which can include fatigue, dry mouth, sleepiness, and nausea,” Smith said.
Patients completed the Brief Pain Inventory–Short Form survey at baseline and then every week. Decrease in pain scores was reported by 59% of the duloxetine- treated patients versus 38% for placebo. Thirty-three percent of the duloxetine group reported at least a 30% decrease in pain severity, and 21% reported at least a 50% decrease in pain severity.
No change in pain score was seen in 30% of the duloxetine group and 34% of placebo patients. Pain was increased in 11% of those taking duloxetine versus 28% of placebo patients. No difference in duloxetine efficacy was observed based on the specific neurotoxic chemotherapy given.
“Patients treated with duloxetine enjoyed a greater decrease in the amount of pain that interfered with general activity, mood, walking, work, enjoyment of life, and social relationships,” Smith told listeners.
Severe (grade 3) nonhematologic toxicity was seen in 11% of those who received duloxetine, and 41% reported moderate (grade 2) toxicity. Grade 2 or higher fatigue was the most common adverse event in the duloxetine-treated patients, reported in 11% versus 3% of placebo patients. Less than 10% experienced fatigue, insomnia, nausea, somnolence, or dizziness.
The incidence of adverse events was lower than in previous trials of duloxetine for diabetic neuropathy, which Smith attributed to the lower starting dose in this trial.
Gabapentin has been used off label for chemotherapy-related peripheral neuropathy, but it causes somnolence, explained Hope Rugo, MD, of the University of California San Francisco, who commented on this paper during a press conference. “Duloxetine doesn’t have that side effect, so it could be advantageous for patients who need treatment for peripheral neuropathy,” Rugo said.
Lavoie Smith EM, Pang H, Cirrincione C, et al. CALGB 170601: a phase III double blind trial of duloxetine to treat painful chemotherapy-induced peripheral neuropathy (CIPN). Presented at: 2012 Annual Meeting of the American Society of Clinical Oncology; June 2012; Chicago, IL. Abstract CRA9013.