Department of Medical Oncology, University of Oxford Churchill Hospital, Oxford, OX3 7LJ, UK.
Invest New Drugs. 2013 Oct;31(5):1228-35. doi: 10.1007/s10637-013-9938-7. Epub 2013 Feb 28.
Although combining targeted agents with conventional, first-line cytotoxic therapy has improved survival outcomes in patients with advanced colorectal cancer, further improvements in outcomes and tolerability are needed.
This phase I study evaluated the feasibility of combining oral pazopanib, an agent that targets multiple proangiogenic factors, with FOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) or CapeOx (oxaliplatin and capecitabine). This phase I study evaluated the optimally tolerated regimen of daily pazopanib (dose-escalated) plus standard FOLFOX6 or CapeOx in patients with advanced colorectal cancer. At the optimally tolerated regimen, each cohort was expanded to further evaluate safety and clinical response.
The optimally tolerated regimens were pazopanib 800 mg plus FOLFOX6 and pazopanib 800 mg plus reduced CapeOx (capecitabine 850 mg/m(2)). The most commonly reported adverse events in the FOLFOX6 cohorts included decreased appetite, neutropenia, diarrhea, peripheral neuropathy, and vomiting. Similarly, the most commonly reported adverse events in the CapeOx cohorts included fatigue, vomiting, and decreased appetite. The overall response rate was 40 % (8/20 patients) in the pazopanib plus FOLFOX6 cohorts and 38 % (8/21 patients) in the pazopanib plus CapeOx cohorts.
Pazopanib combined with FOLFOX6 or reduced CapeOx was adequately tolerated in this patient population.
虽然联合靶向药物与常规的一线细胞毒性疗法已经提高了晚期结直肠癌患者的生存结果，但仍需要进一步改善结果和耐受性。
这项 I 期研究评估了口服帕唑帕尼（一种靶向多种促血管生成因子的药物）联合 FOLFOX6（奥沙利铂、亚叶酸钙和 5-氟尿嘧啶）或 CapeOx（奥沙利铂和卡培他滨）的可行性。这项 I 期研究评估了帕唑帕尼（剂量递增）联合标准 FOLFOX6 或 CapeOx 在晚期结直肠癌患者中的最佳耐受方案。在最佳耐受方案中，每个队列都进行了扩展，以进一步评估安全性和临床反应。
最佳耐受方案为帕唑帕尼 800mg 联合 FOLFOX6 和帕唑帕尼 800mg 联合减少剂量的 CapeOx（卡培他滨 850mg/m2）。FOLFOX6 队列中最常见的不良反应包括食欲下降、中性粒细胞减少、腹泻、周围神经病和呕吐。同样，CapeOx 队列中最常见的不良反应包括疲劳、呕吐和食欲下降。帕唑帕尼联合 FOLFOX6 队列的总缓解率为 40%（20 例患者中有 8 例），帕唑帕尼联合 CapeOx 队列的总缓解率为 38%（21 例患者中有 8 例）。
帕唑帕尼联合 FOLFOX6 或减少剂量的 CapeOx 在该患者人群中具有良好的耐受性。
