Phase I trial using a time-to-event continual reassessment strategy for dose escalation of cisplatin combined with gemcitabine and radiation therapy in pancreatic cancer
Phase I trial using a time-to-event continual reassessment strategy for dose escalation of cisplatin combined with gemcitabine and radiation therapy in pancreatic cancer
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DOI：
10.1200/jco.2004.03.129
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发表时间：
2004-01-15
影响因子：
45.3
通讯作者：
Zalupski, MM
中科院分区：
文献类型：
--
作者：
Muler, JH;McGinn, CJ;Zalupski, MM
本研究的主要目的是确定顺铂的最大耐受剂量，可以添加到全剂量吉西他滨和放射治疗（RT）在patients with pancreatic cancer.Patients和方法19例患者进行了治疗。吉西他滨1，000 mg/m2在28天周期的第1、8和15天给药30分钟以上。第1天和第15天，顺铂继吉西他滨。顺铂的初始剂量水平为30 mg/m2，使用至事件发生时间持续再评估方法递增至目标剂量50 mg/m2。RT在第1周期第1天开始，分次2.4戈伊，总剂量为36戈伊。结果8例患者中有4例在顺铂50 mg/m2剂量水平出现急性剂量限制性毒性反应。接受30和40 mg/m2顺铂剂量水平治疗的患者耐受治疗，无剂量限制性毒性，中位生存期为10.7个月（95% CI，5.4 - 18.2），12.9个月（95% Cl，结论顺铂剂量高达40 mg/m2时，可安全地加用全剂量吉西他滨和适形放疗。事件连续再评估方法试验设计允许快速完成研究并对最大耐受剂量的结论有信心，但与典型的I期设计相比，在最大耐受剂量以上的剂量水平上增加了更多的患者。本研究队列中的局部和全身疾病控制和生存率支持进一步研究基于吉西他滨的RT和联合化疗治疗该疾病。
The primary objective of this study was to determine the maximum-tolerated dose of cisplatin that could be added to full-dose gemcitabine and radiation therapy (RT) in patients with pancreatic cancer.Patients and Methods Nineteen patients were treated. Gemcitabine 1,000 mg/m(2) was administered over 30 minutes on days 1, 8, and 15 of a 28-day cycle. Cisplatin followed gemcitabine on days 1 and 15. The initial dose level of cisplatin was 30 mg/m(2), escalated to a targeted dose of 50 mg/m(2) using Time-to-Event Continual Reassessment Method. RT was initiated on cycle 1, day 1, in 2.4 Gy fractions to a total dose of 36 Gy. A second cycle of chemotherapy was planned following a 1-week rest.Results Four of eight patients experienced acute dose limiting toxicity at the 50 mg/m(2) cisplatin dose level. Patients treated at 30 and 40 mg/m(2) cisplatin dose level tolerated therapy without dose-limiting toxicity, Median survival was 10.7 months (95% Cl, 5.4 to 18.2) for all patients, and 12.9 months (95% Cl, 7.4 to 21.2) for those without metastasis.Conclusion Cisplatin at doses up to 40 mg/m(2) may be safely added to full-dose gemcitabine and conformal RT. The Time-to-Event Continual Reassessment Method trial design allowed rapid completion of the study and confidence in the conclusion about the maximum tolerated dose, but accrued more patients to a dose level above the maximum tolerated dose than the typical phase I design. Local and systemic disease control and survival in this study cohort supports further investigation of gemcitabine-based RT and combination chemotherapy in this disease.