Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer
Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer
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DOI：
10.1200/jco.2001.19.22.4202
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发表时间：
2001-11-15
影响因子：
45.3
通讯作者：
Lawrence, TS
中科院分区：
文献类型：
--
作者：
McGinn, CJ;Zalupski, MM;Lawrence, TS
目的：这个I期试验的主要目的是确定最大耐受剂量的辐射，可以提供给原发性肿瘤同时与全剂量吉西他滨在patients with advanced pancreatic cancer.Patients和方法：37例不可切除（n = 34）或不完全切除胰腺癌（n = 3）进行了治疗。吉西他滨以1,000 mg/m2的剂量静脉输注30分钟，第1、8和15天，28天为一个周期。放射治疗在第1天开始，仅针对原发性肿瘤，不进行预防性淋巴结覆盖。起始辐射剂量为24戈伊，每次1.6-戈伊。通过以0.2戈伊的增量增加分次大小，保持辐射持续时间恒定为3周，实现了逐步升级。第二个周期的吉西他滨单独打算后1周的休息。结果：两个6评估患者经历了剂量限制性毒性试验的最终计划剂量水平（42戈伊，2.8-戈伊分数），4级呕吐和胃/十二指肠溃疡。另外两名患者在这个剂量水平经历了晚期胃肠道毒性，需要手术management.Conclusion：最终剂量调查（42戈伊）不建议进一步研究考虑急性和晚期毒性的发生。然而，基于耐受性、失败模式和生存数据，建议对这种新型的基于吉西他滨的放化疗方法进行II期试验，放射剂量为36戈伊，分次为2.4-戈伊。(C)2001年，美国临床肿瘤学会。
Purpose: The primary objective of this phase I trial was to determine the maximum-tolerated dose of radiation that could be delivered to the primary tumor concurrent with full-dose gemcitabine in patients with advanced pancreatic cancer.Patients and Methods: Thirty seven patients with unresectable (n = 34) or incompletely resected pancreatic cancer (n = 3) were treated. Gemcitabine was administered as a 30-minute intravenous infusion at a dose of 1,000 mg/m(2) an days 1, 8, and 15 of a 28-day cycle. Radiation therapy was initiated on day 1 and directed at the primary tumor alone, without prophylactic nodal coverage. The starting radiation dose was 24 Gy in 1.6-Gy fractions. Escalation was achieved by increasing the fraction size in increments of 0.2 Gy, keeping the duration of radiation constant at 3 weeks. A second cycle of gemcitabine alone was intended after a 1-week rest.Results: Two of six assessable patients experienced dose-limiting toxicity at the final planned dose level of the trial (42 Gy in 2.8-Gy fractions), one with grade 4 vomiting and one with gastric/duodenal ulceration. Two additional patients at this dose level experienced late gastrointestinal toxicity that required surgical management.Conclusion: The final dose investigated (42 Gy) is not recommended for further study considering the occurrence of both acute and late toxicity. However, a phase II trial of this novel gemcitabine-based chemoradiatherapy approach, at a radiation dose of 36 Gy in 2.4-Gy fractions, is recommended on the basis of tolerance, patterns of failure, and survival data. (C) 2001 by American Society of Clinical Oncology.