Rich Tyvin, Harris Jonathan, Abrams R, Erickson B, Doherty M, Paradelo J, Small W, Safran H, Wanebo Harold J
Department of Radiation Oncology, University of Virginia Health Science Center, Charlottesville, Virginia 22908, USA.
Am J Clin Oncol. 2004 Feb;27(1):51-6. doi: 10.1097/01.coc.0000046300.88847.bf.
Unresectable cancer of the pancreas was treated with the combination of weekly paclitaxel and external beam irradiation in an effort to improve palliation and extend life expectancy. One hundred twenty-two patients were entered in a multicentered protocol. Thirteen patients were either ineligible, cancelled, or had delinquent data, thus providing 109 for analysis. Unresectable cancer was based on imaging studies (computed tomography or magnetic resonance imaging), all had histologic proof of adenocarcinoma, and none had evidence of metastatic disease or peritoneal seeding. Image-guided radiotherapy treatment consisted of 50.4 Gy in 28 fractions over 5.5 weeks with coplanar anterior/posterior and lateral ports. An initial dose of 45 Gy was given to fields covering the primary tumor plus the regional peripancreatic, celiac, and porta hepatis lymph nodes. A cone down field was used for the last three fractions to encompass the gross tumor volume with a 1- to 1.5-cm margin. Paclitaxel was administered weekly with irradiation in a dosage of 50 mg/m2 as a 3-hour infusion. The median age was 63 and 53% were female. The Karnofsky performance status was greater than or equal to 80 in 81%. Eighty percent were classified T3 or 4; 20% had N1 disease. The primary tumor was located in the pancreatic head in 65%. Eighty-five percent received all six cycles of paclitaxel per protocol, whereas 93% received irradiation with acceptable protocol variation. Field placement, total dose, fractionation, and overall treatment time were given per protocol in greater than or equal to 90%. Acute toxicity (worst per patient) occurred in 39% with grade III (35% of these were asymptomatic neutropenia), 5% with grade IV, and one patient died of infection during the fourth cycle of chemotherapy (grade V). The median follow-up time for alive patients is 20.6 months (range 5-30). The median survival is 11.2 months (95% CI 10.1, 12.3) with estimated 1- and 2-year survivals of 43% and 13%, respectively. External irradiation plus concurrent weekly paclitaxel is well tolerated when given with large-field radiotherapy. The median survival is better than historical results achieved with irradiation and fluoropyrimidines. These data provide the basis for a new Radiation Therapy Oncology Group trial using paclitaxel and irradiation combined with a second radiation sensitizer, gemcitabine, now under way.
为了改善姑息治疗效果并延长预期寿命，对无法切除的胰腺癌患者采用每周一次紫杉醇联合外照射治疗。122例患者进入多中心研究方案。13例患者不符合条件、退出或数据缺失，因此纳入分析的患者有109例。无法切除的癌症基于影像学检查（计算机断层扫描或磁共振成像），所有患者均有腺癌组织学证据，且均无转移或腹膜种植证据。图像引导放射治疗包括在5.5周内分28次给予50.4 Gy，采用共面的前后位和侧位野。初始剂量45 Gy给予覆盖原发肿瘤及区域胰腺周围、腹腔干和肝门淋巴结的野。最后三次分割使用缩野照射，以1～1.5 cm的边界包绕大体肿瘤体积。紫杉醇在放疗期间每周给药一次，剂量为50 mg/m²，静脉输注3小时。中位年龄为63岁，53%为女性。81%的患者卡氏功能状态评分大于或等于80分。80%的患者为T3或T4期；20%有N1期疾病。65%的原发肿瘤位于胰头。85%的患者按方案接受了全部六个周期的紫杉醇治疗，93%的患者接受了符合方案变异要求的放疗。超过90%的患者野的设置、总剂量、分割次数和总治疗时间符合方案要求。39%的患者发生急性毒性反应（每位患者最严重的反应），其中III级反应占35%（这些患者中35%为无症状性中性粒细胞减少），IV级反应占5%，1例患者在化疗第四个周期死于感染（V级反应）。存活患者的中位随访时间为20.6个月（范围5～30个月）。中位生存期为11.2个月（95%可信区间10.1，12.3），估计1年和2年生存率分别为43%和13%。当与大野放疗联合使用时，外照射加同期每周一次紫杉醇耐受性良好。中位生存期优于既往放疗和氟嘧啶治疗的结果。这些数据为放射肿瘤学组正在进行的一项新试验提供了依据，该试验使用紫杉醇、放疗联合第二种放射增敏剂吉西他滨。
