San Francisco, CA—By improving chemotherapy-induced peripheral neuropathy (CIPN), administration of duloxetine may enable patients with advanced pancreatic cancer to continue their treatment regimen of gemcitabine plus nab-paclitaxel.
In a retrospective examination of 120 patients with pancreatic cancer who received nab-paclitaxel as first-line therapy, 60% had CIPN of any grade. Of those taking duloxetine, CIPN improved or did not worsen in approximately 50%, reported Hidetaka Suzuki, PharmD, Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Japan, at the 2017 Gastrointestinal Cancers Symposium.
“The results of this study suggest the possibility that duloxetine not only improves nab-paclitaxel–related CIPN, but delays its progression. Therefore, it might contribute to continuing nab-paclitaxel with a high relative dose intensity for longer periods of time,” said Dr Suzuki.
The study analyzed 120 patients with unresectable pancreatic cancer who received gemcitabine (1000 mg/m2) plus nab-paclitaxel (125 mg/m2 on days 1, 8, and 15 every 4 weeks) between December 2014 and December 2015. The frequency of CIPN was 60.8% (n = 73) for any grade, and 21.7% (n = 26) for grade ≥2. These rates are similar to those reported in previous studies. The median cumulative dose of nab-paclitaxel until patients manifested CIPN was 776.7 mg/m2.
Duloxetine was prescribed at the discretion of the treating physician. Among the 73 patients who exhibited CIPN, 35 received 20 mg to 60 mg of duloxetine orally once daily, for as long as possible; the remaining patients did not receive it.
Seventeen patients received duloxetine for <4 weeks, with the reasons for discontinuation being patient refusal in 52.9% (n = 9), and adverse effects in 47.1% (n = 8). These adverse effects included nausea, somnolence, fatigue, weakness, ischuria, and dizziness.
Eighteen patients received duloxetine for >4 weeks. The baseline characteristics were similar between this group and the patients who did not receive duloxetine. In patients who received duloxetine for >4 weeks, 9 were treated with 20 mg daily, 7 with 40 mg daily, and 2 with 60 mg daily. Of these 18 patients, CIPN showed improvement in 4 (22.2%) and did not worsen in 12 (66.7%).
The relative dose intensity of nab-paclitaxel following the emergence of CIPN in the duloxetine group was higher than in the no-duloxetine group (63.2% vs 48.2%, respectively; P = .0046). The median treatment duration of nab-paclitaxel following the emergence of CIPN was 210 days in the group receiving duloxetine for >4 weeks, compared with 112 days in the no-duloxetine group (P = .057).