Late effects of low-dose adjuvant chemotherapy in colorectal cancer.

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.

RCT Entities:   Population Interventions Outcomes