Details

Autor(en) / Beteiligte

• Campone, Mario
• Berton‐Rigaud, Dominique
• Joly‐Lobbedez, Florence
• Baurain, Jean‐Francois
• Rolland, Frédéric
• Stenzl, Arnulf
• Fabbro, Michel
• Dijk, Marjan
• Pinkert, Jörg
• Schmelter, Thomas
• Bont, Natasja
• Pautier, Patricia

Titel

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

Ist Teil von

• The oncologist (Dayton, Ohio), 2013-11, Vol.18 (11), p.1190-1191

Ort / Verlag

Durham, NC, USA: AlphaMed Press

Erscheinungsjahr

2013

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Background. 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/m2 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. 摘要 背景. 周围神经病变（PN）已被视为微管靶向制剂的副反应，也是埃博霉素沙戈匹隆（SAG）治疗时观察到的最常见临床相关毒性反应之一。有研究显示乙酰左旋肉碱（ALC）可能预防化疗诱导的PN。我们开展了一项前瞻性、安慰剂（PBO）对照的双盲、随机试验，以明确ALC预防SAG诱导的PN的安全性和疗效。 方法. 卵巢癌（OC）或去势难治性前列腺癌（CRPC）且无神经病变的患者接受SAG（16 mg/m2，静注3小时以上，每3周1次），联合ALC（1 000 mg，每3天1次）或安慰剂（PBO）。 主要终点为两个治疗组在6周或更少周期内的PN发生率。 结果. 共入组150例患者（98例OC，52例CRPC），每个治疗组各75例。总PN发生率在两个治疗组之间未观察到显著差异。ALC组OC患者中≥ 3级PN发生率显著较低。两个治疗组神经病变的中位持续时间相似。两组最佳总缓解率（根据校正后实体瘤缓解评估标准）、基于肿瘤标志物的缓解、时间‐事件变量以及因不良事件（AE）导致的中断治疗结果相当。 结论. 与PBO相比，使用ALC联合SAG并未使总PN发生率出现显著变化。与SAG/PBO组OC患者相比，SAG/ALC组OC患者中3或4级PN发生率显著较低。The Oncologist 2013;18:1190–1191