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A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum

A progress report of National Surgical Adjuvant Breast and Bowel Project protocol R-03

  • Original Contributions
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Diseases of the Colon & Rectum

Abstract

PURPOSE: National Surgical Adjuvant Breast and Bowel Project Protocol R-03 was designed to determine the worth of preoperative chemotherapy and radiation therapy in the management of operable rectal cancer. METHODS: Thus far, 116 patients of an eventual 900 with primary operable rectal cancer have been randomized to receive multimodality therapy to begin preoperatively (59 patients) or identical therapy beginning after curative surgery (57). All patients received seven cycles of 5-fluorouracil (FU)/leucovorin (LV) chemotherapy. Cycles 1 and 4 through 7 used a high-dose weekly FU regimen. In Cycles 2 and 3, FU and low-dose LV chemotherapy was given during the first and fifth week of radiation therapy (5,040 cGy). The preoperative arm (Group 1) received the first three cycles of chemotherapy and all radiation therapy before surgery. The postoperative arm (Group 2) received all radiation and chemotherapy after surgery. Primary study end points included disease-free survival and survival. Secondary end points included local recurrence, primary tumor response to combination therapy, tumor downstaging, and sphincter preservation. RESULTS: Overall treatment-related toxicity was similar in both groups. Although seven preoperative patients had events after randomization that precluded surgery, eight events occurred during an equivalent follow-up period in the postoperative group. No patient was deemed inoperable because of progressive local disease. Sphincter-saving surgery was intended in 31 percent of Group 1 patients and 33 percent of Group 2 patients at the time of randomization. Such surgery was actually performed in 50 percent of the preoperatively treated patients and 33 percent of the postoperatively treated patients. The use of protective colostomy in patients undergoing sphincter-sparing surgery and the development of perioperative complications in all surgical patients were similar in both groups. There was evidence of tumor downstaging in evaluable patients under-going preoperative therapy, with 8 percent of Group 1 patients having had a pathologic complete response. CONCLUSION: These data do suggest that the preoperative chemotherapy and radiation therapy regimen used are, at least, as safe and tolerable as standard postoperative treatment. There is presently a trend to tumor downstaging and sphincter preservation in the preoperative arm. Whether this arm will have greater or lesser survival and long-term toxicity awaits the completion of this relevant study.

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Authors and Affiliations

  1. NSABP, Operations Center, Four Allegheny Center-5th Floor, 15212-5234, Pittsburgh, Pennsylvania

    David M. Hyams M.D., Eleftherios P. Mamounas M.D., D. Lawrence Wickerham M.D., Bernard Fisher M.D. & Norman Wolmark M.D.

  2. National Surgical Adjuvant Breast and Bowel Project Biostatistical Center, University of Pittsburgh, Pittsburgh, Pennsylvania

    Howard Rockette Ph. D., Judy Jones M.S. & H. Sam Wieand Ph.D.

  3. Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania

    Melvin Deutsch M.D.

  4. Department of Surgical Oncology, Roswell Park Cancer Center, Buffalo, New York

    Nicholas Petrelli M.D.

Authors
  1. David M. Hyams M.D.
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  2. Eleftherios P. Mamounas M.D.
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  3. Nicholas Petrelli M.D.
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  4. Howard Rockette Ph. D.
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  5. Judy Jones M.S.
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  6. H. Sam Wieand Ph.D.
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  7. Melvin Deutsch M.D.
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  8. D. Lawrence Wickerham M.D.
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  9. Bernard Fisher M.D.
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  10. Norman Wolmark M.D.
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Additional information

Supported by National Cancer Institute Grants U10-CA-12027 and U10-CA-37377 and American Cancer Society Grant R-13.

Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.

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Hyams, D.M., Mamounas, E.P., Petrelli, N. et al. A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum. Dis Colon Rectum 40, 131–139 (1997). https://doi.org/10.1007/BF02054976

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