Boice J D, Greene M H, Keehn R J, Higgins G A, Fraumeni J F
J Natl Cancer Inst. 1980 Mar;64(3):501-11.
As part of a systematic program to evaluate the late effects of antineoplastic therapy in randomized clinical trials, patients enrolled in the low-dose thio-TEPA (TSPA) and 5-fluoro-2'-deoxyuridine (FdUrd) adjuvant colorectal cancer protocols of the Veterans Administration (VA) Surgical Oncology Group between 1958 and 1964 were studied. All patients received surgery with curative intent; 470 also received TSPA, 176 received FdUrd, and 867 received surgery only. The unique VA system permitted complete follow-up through 1977, with 10,902 person-years of observation accrued among 1,613 male patients (mean survival = 6.8 yr). Expected mortality and cancer incidence were computed by applying U.S. Mortality Statistics and Connecticut Tumor Registry age-, race-, sex-, and calendar time-specific rates to the person-years of observation. The mortality experience of the 3 groups was similar. Overall, there was a significant excess in total mortality (observed/expected = 1,359/553) attributable mainly to colorectal cancer (584/14), arteriosclerotic heart disease (258/215.9), pneumonia (41/17), gastric and duodenal ulcers (15/4), and cirrhosis (14/6). No excess mortality from noncolorectal cancers was apparent, nor were there significant differences by treatment: TSPA (22/22), FdUrd (9/12), and surgery only (50/42). Among 1,402 white patients, no significant excess of incident noncolorectal cancers were observed among patients treated with TSPA (30/31, FdUrd (14/15), or surgery only (63/58). Seven incident cases of leukemia developed (4.1 expected) among all patients of various groups: TSPA (3/1.3), FdUrd (1/0.6), and surgery only (3/2.2). No excess of new primary cancers was observed among 211 nonwhite patients. An inverse relationship between the occurrence of second primary cancer and age at diagnosis, irrespective of therapy, was suggested. The results demonstrated the feasibility of this approach for assessment of late complications of anticancer therapy and suggested no measurable carcinogenic effect following very low doses of TSPA and FdUrd in a population of this size.
作为一项在随机临床试验中评估抗肿瘤治疗远期效应的系统性计划的一部分，对1958年至1964年间参加退伍军人管理局（VA）外科肿瘤学组低剂量硫代替派（TSPA）和5-氟-2'-脱氧尿苷（FdUrd）辅助性结直肠癌方案的患者进行了研究。所有患者均接受了根治性手术；470例还接受了TSPA治疗，176例接受了FdUrd治疗，867例仅接受了手术治疗。独特的VA系统允许对患者进行完整随访直至1977年，1613名男性患者累计观察了10902人年（平均生存期 = 6.8年）。通过将美国死亡率统计数据以及康涅狄格肿瘤登记处特定年龄、种族、性别和日历时间的发病率应用于观察人年数，计算出预期死亡率和癌症发病率。三组患者的死亡情况相似。总体而言，总死亡率显著过高（观察值/预期值 = 1359/553），主要归因于结直肠癌（584/14）、动脉硬化性心脏病（258/215.9）、肺炎（41/17）、胃和十二指肠溃疡（15/4）以及肝硬化（14/6）。未发现非结直肠癌导致的额外死亡，不同治疗组之间也无显著差异：TSPA组（22/22）、FdUrd组（9/12）和仅手术组（50/42）。在1402名白人患者中，接受TSPA治疗（30/31）、FdUrd治疗（14/15）或仅手术治疗（63/58）的患者中，未观察到非结直肠癌发病显著增加。在所有不同组的患者中出现了7例白血病（预期4.1例）：TSPA组（3/1.3）、FdUrd组（1/0.6）和仅手术组（3/2.2）。在211名非白人患者中未观察到新发原发性癌症增加。提示无论接受何种治疗，第二原发性癌症的发生与诊断时的年龄呈负相关。结果证明了这种评估抗癌治疗远期并发症方法的可行性，并表明在如此规模的人群中，极低剂量的TSPA和FdUrd未产生可测量的致癌作用。
