The addition of continuous infusion 5-FU to preoperative radiation therapy increases tumor response, leading to increased sphincter preservation in locally advanced rectal cancer

Christopher H. Crane, John M. Skibber, Elisa H. Birnbaum, Barry W. Feig, Anurag K. Singh, Marc E. Delclos, Edward H. Lin, James W. Fleshman, Howard D. Thames, Ira J. Kodner, Mary Ann Lockett, Joel Picus, Thinh Phan, Anshu Chandra, Nora A. Janjan, Thomas E. Read, Robert J. Myerson

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Abstract

Purpose: To compare the outcome from preoperative chemoradiation (CXRT) and from radiation therapy (RT) in the treatment of rectal cancer in two large, single-institutional experiences. Patients and Methods: Between 1978 and 1995, 403 patients with localized, nonmetastatic, clinically staged T3 or T4 rectal cancer patients were treated with preoperative RT alone at two institutions. Patients at institution 1 (n = 207) were treated with pelvic CXRT exclusively, and patients at institution 2 were treated (except for 8 given CXRT) with pelvic RT alone (n = 196). In addition, a third group (n = 61) was treated with CXRT at institution 2 between 1998 and 2000 after a policy change. Both institutions delivered 45 Gy in five fractions as a standard dose, but institution 2 used 20 Gy in five fractions in selected cases (n = 26). At both institutions, concurrent chemotherapy consisted of a continuous infusion of 5-fluorouracil (5-FU) at a dosage of 1500 mg/m2/week. The end points were response, sphincter preservation (SP), relapse-free survival (RFS), pelvic disease control (PC), and overall survival (OS). Results: Median follow-up was 63 months for all living patients at institution 1 and in the primary group of institution 2. Multivariate analysis of the patients in these groups showed that the use of concurrent chemotherapy improved tumor response (T-stage downstaging, 62% vs. 42%, p = 0.001, and pathologic complete response, 23% vs. 5% p < 0.0001), but did not significantly improve LC, RFS, or OS. Follow-up for the secondary group at institution 2 was insufficient to allow the analysis of these endpoints. In the subset of patients receiving 45 Gy who had rectal tumors ≤6 cm from the anal verge (institution 1: n = 132; institution 2 primary: n = 79; institution 2 secondary: n = 33), there was a significant improvement in SP with the use of concurrent chemotherapy (39% at institution 1 compared with 13% in the primary group at institution 2, p < 0.0001). A logistic regression analysis of clinical prognostic factors indicated that the use of concurrent chemotherapy independently influenced SP in these low tumors (p = 0.002). This finding was supported by a 36% SP rate in the secondary group at institution 2. Thus SP increased after the addition of chemotherapy at institution 2. Conclusions: The use of concurrent 5-FU with preoperative radiation therapy for T3 and T4 rectal cancer independently increases tumor response and may contribute to increased SP in patients with low rectal cancer.

Original languageEnglish
Pages (from-to)84-89
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume57
Issue number1
DOIs
StatePublished - Sep 1 2003

Keywords

  • Chemotherapy
  • Fluorouracil
  • Radiation therapy
  • Rectal neoplasms

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    Crane, C. H., Skibber, J. M., Birnbaum, E. H., Feig, B. W., Singh, A. K., Delclos, M. E., Lin, E. H., Fleshman, J. W., Thames, H. D., Kodner, I. J., Lockett, M. A., Picus, J., Phan, T., Chandra, A., Janjan, N. A., Read, T. E., & Myerson, R. J. (2003). The addition of continuous infusion 5-FU to preoperative radiation therapy increases tumor response, leading to increased sphincter preservation in locally advanced rectal cancer. International Journal of Radiation Oncology Biology Physics, 57(1), 84-89. https://doi.org/10.1016/S0360-3016(03)00532-7