A double-blind, randomized phase II study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy.

Abstract

Peripheral neuropathy (PN) is a recognized side effect of microtubule-targeting agents and the most clinically relevant toxicity observed with the epothilone sagopilone (SAG). Studies suggest that acetyl-L-carnitine (ALC) may prevent chemotherapy-induced PN. We conducted a prospective, placebo (PBO)-controlled, double-blind, randomized trial to investigate the safety and efficacy of ALC for the prevention of SAG-induced PN. Methods. Patients with ovarian cancer (OC) or castration-resistant prostate cancer (CRPC) and no evidence of neuropathy received SAG (16 mg/m(2) intravenously over 3 hours every 3 weeks) with ALC (1,000 mg every 3 days) or placebo (PBO). The primary endpoint was incidence of PN within six or fewer cycles in both treatment groups. Results. Overall, 150 patients enrolled (98 OC patients, 52 CRPC patients), with 75 per treatment arm. No significant difference in overall PN incidence was observed between treatment arms. The incidence of grade ≥3 PN was significantly lower in the ALC arm in OC patients. Median duration of neuropathy was similar between treatment arms. The best overall response (according to the modified Response Evaluation Criteria in Solid Tumors), response according to tumor markers, time-to-event variables, and discontinuations because of adverse events (AEs) were comparable between treatment arms. Conclusion. Administration of ALC with SAG did not result in a significant difference in overall PN incidence compared with a PBO. OC patients in the SAG/ALC arm had a significantly lower incidence of grade 3 or 4 PN compared with OC patients in the SAG/PBO arm.

• Authors: Mario Campone, Dominique Berton-Rigaud, Florence Joly-Lobbedez, Jean-Francois Baurain, Frédéric Rolland, Arnulf Stenzl, Michel Fabbro, Marjan van Dijk, Jörg Pinkert, Thomas Schmelter, Natasja de Bont, Patricia Pautier
• Journal: The oncologist (Oncologist) Vol. 18 Issue 11 Pg. 1190-1 ( 2013) ISSN: 1549-490X [Electronic] England
• PMID: 24105751 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)

Chemical References

• Antineoplastic Agents
• Benzothiazoles
• Epothilones
• Acetylcarnitine
• sagopilone

Topics

• Acetylcarnitine (adverse effects, therapeutic use)
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects, therapeutic use)
• Benzothiazoles (adverse effects, therapeutic use)
• Double-Blind Method
• Epothilones (adverse effects, therapeutic use)
• Female
• Humans
• Male
• Middle Aged
• Ovarian Neoplasms (drug therapy)
• Peripheral Nervous System Diseases (chemically induced, prevention & control)
• Prospective Studies
• Prostatic Neoplasms, Castration-Resistant (drug therapy)