Budiharto Tom, Haustermans Karin, Van Cutsem Eric, Van Steenbergen Werner, Topal Baki, Aerts Raymond, Ectors Nadine, Bielen Didier, Vanbeckevoort Dirk, Goethals Laurence, Verslype Chris
Department of Radiotherapy, University Hospitals Leuven, Leuven, Belgium.
Radiat Oncol. 2008 Sep 22;3:30. doi: 10.1186/1748-717X-3-30.
The primary objective of this study was to determine the maximum tolerated dose (MTD) of escalating doses of radiotherapy (RT) concomitantly with a fixed dose of gemcitabine (300 mg/m2/week) within the same overall treatment time.
Thirteen patients were included. Gemcitabine 300 mg/m2/week was administered prior to RT. The initial dose of RT was 45 Gy in 1.8 Gy fractions, escalated by adding 5 fractions of 1.8 Gy (one/week) to a dose of 54 Gy with a total duration kept at 5 weeks. All patients received a dynamic MRI to assess the pancreatic respiratory related movements. Toxicity was scored using the RTOG-EORTC toxicity criteria.
Three of six patients experienced an acute dose limiting toxicity (DLT) at the 54 Gy dose level. For these patients a grade III gastro-intestinal toxicity (GI) was noted. Patients treated at the 45 Gy dose level tolerated therapy without DLT. The 54 Gy dose level was designated as the MTD and was deemed not suitable for further investigation. Between both dose levels, there was a significant difference in percentage weight loss (p = 0.006) and also in cumulative GI toxicity (p = 0.027). There was no grade 3 toxicity in the 45 Gy cohort versus 4 grade 3 toxicity events in the 54 Gy cohort. The mean dose to the duodenum was significantly higher in the 54 Gy cohort (38.45 Gy vs. 51.82 Gy; p = 0.001).
Accelerated dose escalation to a total dose of 54 Gy with 300 mg/m2/week gemcitabine was not feasible. GI toxicity was the DLT. Retrospectively, the dose escalation of 9 Gy by accelerated radiotherapy might have been to large. A dose of 45 Gy is recommended. Considering the good patient outcomes, there might be a role for the investigation of a fixed dose of gemcitabine and concurrent RT with small fractions (1.8 Gy/day) in borderline resectable or unresectable non-metastatic locally advanced pancreatic cancer.
本研究的主要目的是确定在相同的总治疗时间内，递增剂量的放疗（RT）与固定剂量的吉西他滨（300mg/m²/周）联合使用时的最大耐受剂量（MTD）。
纳入13例患者。在放疗前给予吉西他滨300mg/m²/周。放疗的初始剂量为45Gy，分1.8Gy/次，通过每周增加5次1.8Gy（共增加9Gy）将剂量递增至54Gy，总疗程保持在5周。所有患者均接受动态MRI以评估胰腺呼吸相关运动。使用RTOG-EORTC毒性标准对毒性进行评分。
6例患者中有3例在54Gy剂量水平出现急性剂量限制性毒性（DLT）。这些患者出现了III级胃肠道毒性（GI）。接受45Gy剂量水平治疗的患者耐受治疗，未出现DLT。54Gy剂量水平被指定为MTD，被认为不适合进一步研究。在两个剂量水平之间，体重减轻百分比（p = 0.006）和累积GI毒性（p = 0.027）存在显著差异。45Gy组无3级毒性，而54Gy组有4次3级毒性事件。54Gy组十二指肠的平均剂量显著更高（38.45Gy对51.82Gy；p = 0.001）。
将吉西他滨300mg/m²/周加速剂量递增至总剂量54Gy是不可行的。GI毒性是DLT。回顾性分析，通过加速放疗递增9Gy的剂量可能过大。建议剂量为45Gy。考虑到良好的患者预后，对于可切除边缘或不可切除的非转移性局部晚期胰腺癌，研究固定剂量的吉西他滨与小分割（1.8Gy/天）同步放疗可能具有一定作用。
