Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer
Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer
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DOI：
10.1200/jco.2005.03.6780
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发表时间：
2006-03-01
影响因子：
45.3
通讯作者：
Wolff, R
中科院分区：
文献类型：
--
作者：
Crane, CH;Ellis, LM;Wolff, R
目的研究贝伐单抗联合卡培他滨放化疗的安全性。患者和方法不能手术的胰腺腺癌患者在放疗前2周接受贝伐单抗治疗（50.4 Gy治疗原发肿瘤和大体腺病变），放疗期间每2周接受一次贝伐单抗治疗（2.5、5.0、7.5和10 mg/kg剂量各12例），放疗后直至疾病进展。前6名患者在第14至52天给予卡培他滨（650 mg/m(2)）口服，每日2次；其余患者825 mg/m(2)。结果显著的急性胃肠道（43%为2级；4%为3级）、手足综合征（21%为2级）和短暂的血液学（8%为3级或以上）事件在方案规定的卡培他滨2级毒性降低（43%的患者）中并不常见。在最初治疗的30名患者中，3名患者有肿瘤相关的十二指肠溃疡出血，1名患者有十二指肠穿孔。在最后的18例患者中，排除肿瘤累及十二指肠的患者后，没有发生额外的出血事件。46例可评估的患者中有9例（20%）在6.2个月的中位进展前证实部分缓解。4例患者行胰十二指肠切除术，无围手术期并发症。从方案治疗开始，中位生存期为11.6个月（95% CI, 9.6 - 13.6）。结论贝伐单抗并发治疗对相对耐受良好的放化疗方案的急性毒性没有显著增加。然而，当肿瘤累及十二指肠黏膜时，放射场溃疡和出血可能与贝伐单抗有关。令人鼓舞的疗效终点表明贝伐单抗与放化疗的进一步研究是有必要的。
Purpose To study the safety of bevacizumab with capecitabine-based chemoradiotherapy.Patients and Methods Patients with inoperable pancreatic adenocarcinoma received bevacizumab 2 weeks before radiotherapy (50.4 Gy treating the primary tumor and gross adenopathy), every 2 weeks during radiotherapy (12 patients each at 2.5, 5.0, 7.5, and 10 mg/kg), and after radiotherapy until disease progression. Capectabine was administered on days 14 through 52 (650 mg/m(2) orally twice daily for the first six patients; 825 mg/m(2) for the remaining patients).Results Significant acute gastrointestinal (43% grade 2; 4% grade 3), hand and foot syndrome (21% grade 2), and transient hematologic (8% grade 3 or greater) events were uncommon with protocol mandated dose reductions of capecitabine grade 2 toxicity (43% of patients). Among the first 30 patients treated, three patients had tumor-associated bleeding duodenal ulcers, and one had a contained duodenal perforation. No additional bleeding events occurred among the final 18 patients after patients with duodenal involvement by tumor were excluded. Nine (20%) of 46 assessable patients had confirmed partial responses until distant progression for a median of 6.2 months. Four patients have undergone pancreaticoduodenectomy without perioperative complication. The median survival was 11.6 months (95% CI, 9.6 to 13.6), from the start of protocol therapy.Conclusion Concurrent bevacizumab did not significantly increase the acute toxicity of a relatively well-tolerated chemoradiotherapy regimen. However, ulceration and bleeding in the radiation field possibly related to bevacizumab occurred when tumor involved the duodenal mucosa. The encouraging efficacy end points suggest that the further study of bevacizumab with chemoradiotherapy is warranted.