Scholarlink

<p>Lurbinectedin and irinotecan showed synergistic antitumor activity when combined in preclinical studies, and have non-completely overlapping toxicity profiles. A two-stage phase I/II trial was designed to evaluate the combination. The first (dose escalation) stage of the trial assessed two schedules, lurbinectedin on Day (D)1 plus irinotecan on D1,D8 or D1 every three weeks in 83 patients with relapsed advanced solid tumors. Two recommended doses (RDs) were defined for lurbinectedin on D1 plus irinotecan on D1,D8: lurbinectedin 2.0&#xa0;mg/m<sup>2</sup> plus irinotecan 75&#xa0;mg/m<sup>2</sup>, and lurbinectedin 3.0&#xa0;mg/m<sup>2</sup> plus irinotecan 40&#xa0;mg/m<sup>2</sup>, both with primary growth factor prophylaxis. No RD was defined for lurbinectedin on D1 plus irinotecan on D1. Lurbinectedin on D1 plus irinotecan on D1,D8 q3wk showed a manageable safety profile at the RDs, with most common toxicities being myelosuppression, fatigue and gastrointestinal disorders. No toxic deaths occurred. Thirteen confirmed partial responses and 24 disease stabilizations ≥ 4&#xa0;months were found at all dose levels, including the RDs. Compared to other tumor types, antitumor activity was higher in small cell lung cancer (SCLC), soft tissue sarcoma (synovial), endometrial carcinoma, glioblastoma and pancreatic adenocarcinoma. No major pharmacokinetic interaction was found between lurbinectedin and irinotecan. The second (expansion) stage of the trial is evaluating the RD of lurbinectedin 2.0 mg/m<sup>2</sup> plus irinotecan 75 mg/m<sup>2</sup> with primary growth factor prophylaxis in selected advanced solid tumors. An ongoing phase III trial is also evaluating the combination in second-line SCLC after prior platinum-containing chemotherapy. Trial registration number: NCT02611024 (Nov 20, 2015).</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Phase I results on the efficacy, safety and pharmacokinetics of lurbinectedin and irinotecan in advanced solid tumors

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月1日

查看全文
  • Alejandro Falcón,
  • Santiago Ponce,
  • Gregory M. Cote,
  • Ana Gil,
  • Jessica J. Lin,
  • Bruno Bockorny,
  • Julia Martínez,
  • Carmen Kahatt,
  • Sara Martinez,
  • Pablo Zubiaur,
  • Mariano Siguero,
  • Martin Cullell-Young,
  • Javier Jiménez,
  • Jon Zugazagoitia,
  • Luis Paz-Ares

摘要

Lurbinectedin and irinotecan showed synergistic antitumor activity when combined in preclinical studies, and have non-completely overlapping toxicity profiles. A two-stage phase I/II trial was designed to evaluate the combination. The first (dose escalation) stage of the trial assessed two schedules, lurbinectedin on Day (D)1 plus irinotecan on D1,D8 or D1 every three weeks in 83 patients with relapsed advanced solid tumors. Two recommended doses (RDs) were defined for lurbinectedin on D1 plus irinotecan on D1,D8: lurbinectedin 2.0 mg/m2 plus irinotecan 75 mg/m2, and lurbinectedin 3.0 mg/m2 plus irinotecan 40 mg/m2, both with primary growth factor prophylaxis. No RD was defined for lurbinectedin on D1 plus irinotecan on D1. Lurbinectedin on D1 plus irinotecan on D1,D8 q3wk showed a manageable safety profile at the RDs, with most common toxicities being myelosuppression, fatigue and gastrointestinal disorders. No toxic deaths occurred. Thirteen confirmed partial responses and 24 disease stabilizations ≥ 4 months were found at all dose levels, including the RDs. Compared to other tumor types, antitumor activity was higher in small cell lung cancer (SCLC), soft tissue sarcoma (synovial), endometrial carcinoma, glioblastoma and pancreatic adenocarcinoma. No major pharmacokinetic interaction was found between lurbinectedin and irinotecan. The second (expansion) stage of the trial is evaluating the RD of lurbinectedin 2.0 mg/m2 plus irinotecan 75 mg/m2 with primary growth factor prophylaxis in selected advanced solid tumors. An ongoing phase III trial is also evaluating the combination in second-line SCLC after prior platinum-containing chemotherapy. Trial registration number: NCT02611024 (Nov 20, 2015).