Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer?
Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer?
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DOI：
10.1016/s0360-3016(01)02740-7
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发表时间：
2002-04-01
影响因子：
7
通讯作者：
Janjan, NA
中科院分区：
文献类型：
--
作者：
Crane, CH;Abbruzzese, JL;Janjan, NA
目的：回顾性比较并发吉西他滨为基础的放化疗与并发5-氟尿嘧啶（5-FU）为基础的放化疗在不可切除的胰腺癌patients with unremotable pancreatic cancer.Patients和Methods的毒性和疗效：1996年9月至2000年5月，114例局部不可切除的胰腺癌患者进行了同步放化疗。局部晚期不可切除的疾病定义为低密度肿瘤与上级肠系膜动脉（SMA）或腹腔动脉接触，或上级肠系膜-门静脉汇合处闭塞。选择53例患者接受吉西他滨（250-500 mg/m2），每周7个周期，同时进行放疗（中位剂量30戈伊，范围30-33戈伊，分10-11次）。其余61例患者接受5-FU（200-304 mg/m2）持续输注，同时接受放疗（30戈伊，分10次）。对原发肿瘤和局部病灶进行放射治疗。接受吉美他滨治疗的患者和接受5-FU治疗的患者具有相似的平均Karnofsky体力状态（KPS，89% vs. 86%）、肿瘤分级分布（43% vs. 33%低分化）和体重减轻百分比（所有p = NS）。然而，接受吉西他滨治疗的患者的中位最大肿瘤横截面积显著更大（TA，8.8 cm（2）vs. 5.7 cm（2），p = 0.046），并且明显更年轻（中位年龄60岁vs. 68岁，p < 0.001）。重度急性毒性（ST）定义为需要住院超过5天的毒性、粘膜溃疡伴出血、超过3次吉西他滨剂量删除或5-FU停药，或导致手术干预或死亡的毒性。采用Kaplan-Meier分析计算影像学局部进展（LP）率、远处转移（DM）率和总生存率（OS）。结果：接受吉西他滨治疗的患者在治疗期间发生ST的比例（23%对2%，p < 0.0001）明显高于接受5-FU治疗的患者。吉西他滨治疗患者的10个月LP率（62% vs. 61%）、10个月DM率（55% vs. 47%）、1年OS率（42% vs. 28%）和中位OS持续时间（11个月vs. 9个月）与5 FU治疗患者相似（所有p = NS）。5例接受吉西他滨治疗的患者和1例接受5-FU治疗的患者在放化疗后接受了边缘阴性胰腺癌切除术。3例患者有一个短段（长度小于或等于1 cm）的低密度肿瘤邻接SMA，1例累及肝总动脉，1例上级肠系膜静脉短段闭塞，适合静脉切除和重建。另1例患者被认为存在与SMA周围肿瘤不连续的炎性变化，治疗后消退。TA >10 cm（2）（p = 0.03）和分化差（p = 0.07）与生存期较差相关;然而，其他因素，如KPS和体重减轻> 10%和年龄并不影响OS。结论：尽管选择了更健康的患者接受吉西他滨治疗，但严重毒性发生率明显高于5-FU。同时使用吉西他滨的中位生存期和1年生存期无显著差异;然而，治疗的肿瘤明显更大。此外，少数动脉受累最小的患者，其疾病符合我们对不可切除疾病的放射学定义，在接受基于吉西他滨的放化疗治疗后，切缘阴性。这些可能的获益和高发生率的严重毒性定义了通过该给药方案给予的基于吉西他滨的同步放化疗的非常窄的治疗指数。(C)2002年爱思唯尔科技有限公司
Purpose: To retrospectively compare the toxicity and efficacy of concurrent gemcitabine-based chemoradiation with that of concurrent 5-fluorouracil (5-FU)-based chemoradiation in patients with unresectable pancreatic cancer.Patients and Methods: Between September 1996 and May 2000, 114 patients with localized unresectable adenocarcinoma of the pancreas were treated with concurrent chemoradiation. Locally advanced unresectable disease was defined as low-density tumor in contact with the superior mesenteric artery (SMA) or celiac artery, or occlusion of the superior mesenteric-portal venous confluence. Fifty-three patients were selected to receive gemcitabine in 7 weekly cycles (250-500 mg/m(2)) with concurrent radiotherapy (median dose 30 Gy, range 30-33 Gy in 10-11 fractions). The remaining 61 patients received continuous-infusion 5-FU (200-304 mg/m(2)) with concurrent radiotherapy (30 Gy in 10 fractions). Radiotherapy was delivered to the primary tumor and regional lymphatics. Patients receiving gemeitabine and those receiving 5-FU had a similar mean Karnofsky performance status (KPS, 89 % vs. 86 %), distribution of tumor grade (43 % vs. 33 % poorly differentiated), and percent weight loss (all p = NS). However, patients treated with gemcitabine had a significantly larger median maximum cross-sectional tumor area (TA, 8.8 cm(2) vs. 5.7 cm(2), p = 0.046) and were significantly younger (median age 60 vs. 68 years, p < 0.001). Severe acute toxicity (ST) was defined as toxicity requiring a hospital stay of more than 5 days, mucosal ulceration with bleeding, more than 3 dose deletions of gemcitabine or discontinuation of 5-FU, or toxicity resulting in surgical intervention or death. Kaplan-Meier analysis was used to calculate the actuarial rate of local progression on imaging (LP), the rate of distant metastasis (DM), and the overall survival (OS) rate. The imaging was reviewed in resected patients.Results: Patients receiving gemcitabine developed significantly more ST during treatment (23% vs. 2%, p < 0.0001) than did those receiving 5-FU. Patients treated with gemcitabine had a similar 10-month LP rate (62% vs. 61%), 10-month DM rate (55% vs. 47%), 1-year OS rate (42% vs. 28%), and median OS duration (11 months vs. 9 months) to patients treated with 5 FU (all p = NS). Five patients who received gemcitabine and 1 patient who received 5-FU underwent margin-negative pancreaticoduodenectomy after chemoradiation. Three patients had a short segment (less than or equal to 1 cm in length) of low-density tumor abutting the SMA, 1 had involvement of the common hepatic artery, and I had a short-segment occlusion of the superior mesenteric vein, amenable to venous resection and reconstruction. The other patient was thought to have inflammatory changes discontiguous with the tumor surrounding the SMA, which resolved after therapy. TA >10 cm(2) (p = 0.03) and poor differentiation (p = 0.07) were associated with a worse survival duration; however, other factors, such as KPS and weight loss > 10 % and age did not influence OS.Conclusion: Despite the selection of healthier patients to receive gemcitabine, there was a significantly higher severe toxicity rate than with 5-FU. The median and 1-year survivals were not significantly different with the use of concurrent gemcitabine; however, the tumors treated were significantly larger. Additionally, a small number of patients with minimal arterial involvement whose disease met our radiographic definition of unresectable disease had margin-negative resections after treatment with gemcitabine-based chemoradiation. These possible benefits and the high rate of severe toxicity define a very narrow therapeutic index for concurrent gemcitabine-based chemoradiation given by this schedule of administration. (C) 2002 Elsevier Science Inc.