Related Experiment Video
Updated: Apr 30, 2026
Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity
Published on: April 26, 2012
Alliance A221805: Duloxetine to Prevent Oxaliplatin-Induced Chemotherapy-Induced Peripheral Neuropathy: A Randomized,
Ellen M Lavoie Smith1, Minji Lee2, Mary R Scott1
1University of Alabama at Birmingham, Birmingham, AL.
Purpose:
The primary objective of this randomized, double-blind, placebo-controlled, multicenter phase II study (Alliance A221805) was to screen two doses of duloxetine for preventing sensory oxaliplatin-induced peripheral neuropathy (OIPN).
Methods:
Participants were randomly assigned 1:1:1 to receive once daily 30 mg duloxetine, 60 mg duloxetine, or placebo. Eligible participants had stage II to III colorectal cancer and no baseline neuropathy, had Eastern Cooperative Oncology Group performance status 0-2, were age 25 years and older, and received oxaliplatin via one of the following doses and schedules: 85 mg/m2 every 2 weeks (6 or 12 doses) or 130 mg/m2 every 3 weeks (4 doses). Duloxetine/placebo was taken once daily beginning day 1 of cycle 1 and continued for 17 weeks. The primary end point, a composite response reflecting sensory OIPN symptom severity and onset, was measured in weeks 19-21 using a validated participant-reported outcome survey assessing extremity numbness, tingling, and pain. Response was defined as a participant-reported highest score of ≤2 (ie, 1 = not at all; 2 = a little) on survey items. To be evaluable for the response end point, eligible participants must have initiated oxaliplatin and submitted ≥1 postbaseline OIPN survey.
Results:
Of the 199 participants (n = 66, 30 mg duloxetine; n = 66, 60 mg duloxetine; n = 67, placebo), 46, 47, and 50 (N = 143, 71.8%), respectively, were evaluable for primary end point analysis based on modified intention-to-treat criteria. Participant mean age was 55.1 years (standard deviation = 10.4). Most were White (n = 113, 80.7%) and male (n = 82, 58.6%). The proportion of responders among those receiving placebo (68.0%) was similar to those receiving duloxetine 30 mg (65.2%) or 60 mg (66.0%). Duloxetine adherence rates, measured via pill counts-30 mg (54%), 60 mg (57%), and placebo (59%) groups-were low (<75%).
Conclusion:
Duloxetine is not more promising than placebo for preventing sensory OIPN.
Insights
This study found duloxetine did not prevent oxaliplatin-induced peripheral neuropathy (OIPN) in colorectal cancer patients. Adherence to duloxetine was low, suggesting it is not a promising preventative treatment for OIPN.
Area of Science:
- Oncology
- Pharmacology
- Neurology
Background:
- Oxaliplatin is a key chemotherapy agent for colorectal cancer.
- Oxaliplatin-induced peripheral neuropathy (OIPN) is a common and dose-limiting side effect.
- Preventative strategies for OIPN are crucial for maintaining treatment efficacy and patient quality of life.
Purpose of the Study:
- To evaluate the efficacy of two doses of duloxetine in preventing sensory oxaliplatin-induced peripheral neuropathy (OIPN).
- To compare duloxetine 30 mg and 60 mg daily against a placebo for OIPN prevention in colorectal cancer patients.
Main Methods:
- A randomized, double-blind, placebo-controlled, multicenter phase II study (Alliance A221805) was conducted.
- Participants with stage II-III colorectal cancer received oxaliplatin and were randomized to duloxetine (30 mg or 60 mg daily) or placebo for 17 weeks.
- The primary endpoint assessed sensory OIPN severity and onset using participant-reported outcomes in weeks 19-21.
Main Results:
- A total of 199 participants were enrolled; 143 were evaluable for the primary endpoint.
- The proportion of responders (indicating minimal OIPN symptoms) was similar across placebo (68.0%), duloxetine 30 mg (65.2%), and duloxetine 60 mg (66.0%) groups.
- Duloxetine adherence rates were low, below 75% across all groups.
Conclusions:
- Duloxetine demonstrated no significant benefit over placebo in preventing sensory oxaliplatin-induced peripheral neuropathy.
- Low adherence rates may have impacted the study's ability to detect potential efficacy.
- Further research into effective OIPN preventative strategies is warranted.
Related Concept Videos
01:27Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists
01:28Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
01:29Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists
Phenothiazines, such as prochlorperazine...
01:24Drugs for Peptic Ulcer Disease: Sucralfate as Mucosal Protective Agents
In this scenario, mucosal protective agents like sucralfate play an essential role. Sucralfate, a complex of sulfated sucrose and aluminum hydroxide, demonstrates its usefulness in acidic conditions,...
01:17Drugs for Treatment of Diarrhea-Predominant IBS
Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT3 antagonist, works by slowing the movement of stools in the gut, reducing bowel...
01:21Chemotherapy-Induced Nausea and Vomiting: Cannabinoids
Two synthetic agonists of THC,...