ASCO: Cymbalta Tames Post-Chemo Pain

MedPage Today Link

By Crystal Phend, Senior Staff Writer, MedPage TodayPublished: June 04, 2012
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.

Action Points

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• The antidepressant duloxetine (Cymbalta) appears to cut down on the numbness and tingling associated with taxane or platinum-based chemotherapy.
• Note that duloxetine is the first drug to work against this chronic neuropathy in a clinical trial.

CHICAGO -- The antidepressant duloxetine (Cymbalta) appears to cut down on the numbness and tingling associated with taxane or platinum-based chemotherapy, according to clinical trial results.
Pain from chemotherapy-induced peripheral neuropathy and its interference with daily life fell significantly with the drug, Ellen Lavoie Smith, PhD, of the University of Michigan School of Nursing in Ann Arbor, and colleagues found.
A clinically significant 30% or greater reduction in pain scores occurred in 33% of duloxetine-treated patients compared with 17% of placebo-treated patients, they reported here at the American Society of Clinical Oncology meeting.
That makes duloxetine the first drug to work against this chronic neuropathy in a clinical trial, Smith noted at an ASCO press conference.
Some other drugs, such as tricyclic antidepressants and gabapentin, are commonly used but haven't been proven in randomized trials for neuropathy, she told MedPage Today.
Duloxetine, which is a serotonin-norepinephrine reuptake inhibitor, likely works by increasing the amount of some pain-inhibiting neurochemicals in the brain, such as dopamine, Smith noted.
The study included 220 patients (mostly breast and gastrointestinal cancer survivors) with peripheral neuropathy induced by paclitaxel or oxaliplatin (Eloxatin) chemotherapy who were randomized to double-blind treatment with duloxetine or placebo.
Duloxetine dosing started at 30 mg daily for the first week then increased to 60 mg for 4 weeks.
The pain scores fell in both groups over the course of treatment, though significantly more with the antidepressant. Scores on the Brief Pain Inventory-Short Form fell by a mean of 1.09 points compared with 0.33 in the placebo group (P=0.004).
The impact of this pain on daily life appeared to improve too, with interference scores summed across general activity, mood, walking, normal work, relationships, sleep, and enjoyment of life declining significantly more with duloxetine (P=0.015).
The majority of patients had at least some pain reduction with duloxetine (59% versus 38% with placebo). Duloxetine halved pain in 21% of patients compared with 9% experiencing the same reduction on placebo.
The drug appeared well tolerated overall with fewer adverse events than seen in prior trials of duloxetine for diabetic neuropathy, which Smith attributed to the lower starting dose in her trial.
Severe adverse events occurred in 7%, and 11% dropped out due to side effects. The most common side effect with duloxetine was fatigue, at 7%. Somnolence, dizziness, nausea, and insomnia were uncommon with duloxetine.
That safety profile is an advantage compared with gabapentin, noted Hope Rugo, MD, from the University of California San Francisco.
"The main issue for breast cancer patients [for whom taxane treatment is standard of care] is that gabapentin, which we've had success with despite its lack of a randomized trial, causes somnolence," she told MedPage Today. "[Duloxetine] doesn't have that side effect, so it could be really advantageous for patients who need treatment for neuropathy."
The next step is figuring out predictors of response, Smith said.
"We have made a step forward," commented Nicholas J. Vogelzang, MD, of the Comprehensive Cancer Centers of Nevada in Las Vegas and US Oncology, who moderated ASCO briefing.
The problem of treatment-induced neuropathy is common with the taxanes and platinum chemotherapy drugs and can be quite debilitating, he noted.
"It's an important quality-of-life concern for our patients," Vogelzang told MedPage Today. "I'm certainly going to try this as soon as I get back in the office."

The study was supported by the NCI and Lilly Pharmaceuticals.
Smith reported no conflicts of interest.

Primary source: American Society of Clinical Oncology
Source reference:
Smith EML, et al "CALGB 170601: A phase III double blind trial of duloxetine to treat painful chemotherapy-induced peripheral neuropathy (CIPN)" ASCO 2012; Abstract CRA9013.