Future directions in adjuvant therapy for rectal cancer.
The US National Cancer Institute Gastrointestinal Intergroup has contributed to the development of chemotherapy and radiation regimens for the treatment of stage II and III rectal cancer. The first Intergroup trial demonstrated improvement in relapse-free and overall survival for patients who received protracted venous infusion fluorouracil (5-FU) with radiation compared to those treated with bolus 5-FU. The second trial, INT 0114, demonstrated that there was no difference among four regimens, including 5-FU with or without leucovorin or levamisole (Ergamisol) vs three drugs given as concomitant therapy. High-risk (T3, N+; T4) and low-risk (T1/2, N+; T3, N0) tumor categories were identified, revealing significant differences in 5- and 7-year survival rates. Risk of local failure was also greater in the high-risk group. Pathologic assessment of lymph nodes in the surgical specimens had an important impact on these trial results. Relapse-free and overall survival were significantly different among the lymph node-negative patients, as determined by the number of lymph nodes examined. The National Surgical Adjuvant Breast and Bowel Project trials (R-01, R-02) have shown that the addition of radiation does not affect disease-free or overall survival but improves local recurrence rates. Future trials will explore use of newer agents, including capecitabine (Xeloda), irinotecan, and oxaliplatin. In addition, prospective evaluation of laboratory correlates, including molecular markers, will be integrated into trial design.
Clinical Investigations Program, Northwestern University Medical School, The Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, USA. a-benson@northwestern.edu
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D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000008:administration & dosage; D005544:Forecasting; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy
D009944:Organoplatinum Compounds; D005472:Fluorouracil