Crane Christopher H, Winter Kathryn, Regine William F, Safran Howard, Rich Tyvin A, Curran Walter, Wolff Robert A, Willett Christopher G
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
J Clin Oncol. 2009 Sep 1;27(25):4096-102. doi: 10.1200/JCO.2009.21.8529. Epub 2009 Jul 27.
The primary objective of this study was to assess the 1-year survival of patients with locally advanced, unresectable pancreatic cancer treated with the combination of bevacizumab, capecitabine, and radiation. Secondary end points were toxicity, progression-free survival (PFS), and response rate (RR).
Patients with locally advanced pancreatic cancer without duodenal invasion were treated with 50.4 Gy per 28 fractions to the gross tumor with concurrent capecitabine 825 mg/m(2) orally twice daily on days of radiation and bevacizumab 5 mg/kg on days 1, 15, and 29 followed by maintenance gemcitabine 1 g/m(2) weekly for 3 weeks and bevacizumab 5 mg/kg every 2 weeks, both in 4-week cycles until progression. Treatment plans were reviewed for quality assurance (QA).
Between January 2005 and February 2006, 82 eligible patients were treated. The median and 1-year survival rates were 11.9 months (95% CI, 9.9 to 14.0 months) and 47% (95% CI, 36% to 57%). Median PFS was 8.6 months (95% CI, 6.9 to 10.5), and RR was 26%. Overall, 35.4% of patients had grade 3 or greater treatment-related gastrointestinal toxicity (22.0% during chemoradiotherapy, 13.4% during maintenance chemotherapy). Unacceptable radiotherapy protocol deviations (ie, inappropriately generous volume contoured) correlated with grade 3 or greater gastrointestinal toxicity during chemoradiotherapy (45% v 18%; adjusted odds ratio, 3.7; 95% CI, 0.98 to 14.1; P = .05).
The addition of bevacizumab to chemoradiotherapy followed by bevacizumab and gemcitabine resulted in a similar median survival to previous Radiation Therapy Oncology Group studies in patients with locally advanced pancreatic cancer. Prospective QA may help limit toxicity in future trials.
本研究的主要目的是评估接受贝伐单抗、卡培他滨和放疗联合治疗的局部晚期、不可切除胰腺癌患者的1年生存率。次要终点为毒性、无进展生存期（PFS）和缓解率（RR）。
无十二指肠侵犯的局部晚期胰腺癌患者接受总剂量50.4 Gy、分28次照射，照射范围为大体肿瘤，同时在放疗日口服卡培他滨825 mg/m²，每日2次，在第1、15和29天静脉注射贝伐单抗5 mg/kg，随后每周静脉注射吉西他滨1 g/m²，共3周，每2周静脉注射贝伐单抗5 mg/kg，均每4周为1个周期，直至病情进展。对治疗计划进行质量保证（QA）审查。
2005年1月至2006年2月，82例符合条件的患者接受了治疗。中位生存期和1年生存率分别为11.9个月（95%可信区间，9.9至14.0个月）和47%（95%可信区间，36%至57%）。中位PFS为8.6个月（95%可信区间，6.9至10.5），RR为26%。总体而言，35.4%的患者出现3级或更高级别的治疗相关胃肠道毒性（放化疗期间为22.0%，维持化疗期间为13.4%）。不可接受的放疗方案偏差（即靶区勾画过大）与放化疗期间3级或更高级别的胃肠道毒性相关（45%对18%；校正比值比，3.7；95%可信区间，0.98至14.1；P = 0.05）。
在放化疗基础上加用贝伐单抗，随后使用贝伐单抗和吉西他滨，局部晚期胰腺癌患者的中位生存期与既往放射肿瘤学组的研究相似。前瞻性QA可能有助于在未来试验中限制毒性。
