Campone, M., Berton-Rigaud, D., Joly-Lobbedez, F., Baurain, J.-F., Rolland, F., Stenzl, A., . . . Pautier, P. (2013). 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. Oncologist, 18, 1190–1191. 

To investigate if the addition of acetyl-L-carnitine (ALC) to sagopilone (SAG) in patients with ovarian cancer (OC) and castration-resistant prostate cancer (CRPC) reduced the overall incidence of SAG-induced peripheral neuropathy (PN) compared to SAG and placebo, and to evaluate the safety and efficacy of ALC-SAG compared to SAG-placebo

Patients were randomized to treatment and placebo-controlled arms. All patients received a three-hour infusion every three weeks of SAG 16 mg/m² either with oral ALC (1000 mg) three times a day or oral placebo three times a day for six treatment cycles. ALC or placebo was continued for 30–33 days after the last SAG treatment. Patients with CRPC received oral prednisone 5 mg every two days as standard of care for quality of life.

• N = 111 completed study (n = 53 [ALC-SAG arm], n = 58 [SAG-placebo arm]) 
• MEDIAN AGE = 62 years
• AGE RANGE = 29–82 years
• MALES 35%, FEMALES 65% (out of total N = 150 enrolled) 
• KEY DISEASE CHARACTERISTICS: Metastatic/advanced Disease; OC and CRPC patients had no evidence of PN at enrollment.
• OTHER KEY SAMPLE CHARACTERISTICS: Ovarian cancer International Federation of Gynecology and Obstetrics (FIGO) grades IV (18%), III (69%), II (6%), I (7%); the CRPC median Gleason total score was 8; patients with CRPC taking prednisone 5 mg

• SITE: Multi-site    
• SETTING TYPE: Unknown  
• LOCATION: Europe

• PHASE OF CARE: Active treatment
• APPLICATIONS: Elder care, palliative care

Phase-II, prospective, placebo-controlled, double-blind, randomized trial

• PN was evaluated for time to incidence, time to recovery, and grade of neuropathy within six or fewer cycles.
• Measurement tools/instruments for evaluation of PN not described
• Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor size.
• CA-125 blood test
• Prostate-specific antigen (PSA) blood test

No difference in the incidence or median duration of PN existed in either arm. No difference existed in best overall response, tumor markers, time-to-event variables (progression free survival or time to progression), or discontinuations because of adverse events in either arm. Slightly more serious adverse events and grade 3–4 adverse events were reported in the SAG-placebo arm. ALC reduced the incidence of grade 3–4 PN in patients in the SAG-ALC arm compared to patients in the the SAG-placebo arm; however, actual statistical results were not reported.

ALC given concurrently with SAG in patients with advanced OC was reported to reduce the incidence of grade 3–4 PN after six cycles of treatment; however, no results showing statistical significance were provided.

• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Subject withdrawals ≥ 10% (26%)
• Study methods poorly described
• PN evaluation tool not provided
• Number of cycles and types of prior regimens in sample not described
• Inclusion/exclusion criteria not described
• Statistical methods for analysis of data and significance not described but depicted in tables
• Patient with CRPC on prednisone could potentially confound results
• No report of grades or types/frequencies of adverse events in either group
• No information on what was used as the placebo

ALC concurrently with SAG after six cycles reduced the incidence of grade 3–4 PN in patients with advanced OC. No benefit was observed in patients with CRPC or in reducing the incidence of grade 1–2 for either patients with OC or CRPC. Further randomized, controlled trials are needed to determine the benefits, duration of benefits, and quality of life for ALC-SAG or other neurotoxic regimens in diverse tumor types.