Effective surgical adjuvant therapy for high-risk rectal carcinoma

J. E. Krook, C. G. Moertel, L. L. Gunderson, H. S. Wieand, R. T. Collins, R. W. Beart, T. P. Kubista, Thomas Elmer Witzig, W. C. Meyers, J. A. Mailliard, D. I. Twito, R. F. Morton, M. H. Veeder, T. E. Witzig, S. Cha, C. Vidyarthi

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Abstract

Background. Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival. In a previous study, combined radiation and chemotherapy improved survival significantly as compared with surgery alone, but not as compared with adjuvant radiation, which many regard as standard therapy. We designed a combination regimen to optimize the contribution of chemotherapy, decrease recurrence, and improve survival as compared with adjuvant radiation alone. Methods. Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were randomly assigned to postoperative radiation alone (4500 to 5040 cGy) or to radiation plus fluorouracil, which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine (methyl-CCNU). Results. After a median follow-up of more than seven years, the combined therapy had reduced the recurrence of rectal cancer by 34 percent (P = 0.0016; 95 percent confidence interval, 12 to 50 percent). Initial local recurrence was reduced by 46 percent (P = 0.036; 95 percent confidence interval, 2 to 70 percent), and distant metastasis by 37 percent (P = 0.011; 95 percent confidence interval, 9 to 57 percent). In addition, combined therapy reduced the rate of cancer-related deaths by 36 percent (P = 0.0071; 95 percent confidence interval, 14 to 53 percent) and the overall death rate by 29 percent (P = 0.025; 95 percent confidence interval, 7 to 45 percent). Its acute toxic effects included nausea, vomiting, diarrhea, leukopenia, and thrombocytopenia. These effects were seldom severe. Severe, delayed treatment-related reactions, usually small-bowel obstruction requiring surgery, occurred in 6.7 percent of all patients receiving radiation, and the frequencies of these complications were comparable in both treatment groups. Conclusions. The combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil-based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis as compared with postoperative radiation alone.

Original languageEnglish (US)
Pages (from-to)709-715
Number of pages7
JournalNew England Journal of Medicine
Volume324
Issue number11
StatePublished - 1991

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Carcinoma
Radiation
Fluorouracil
Confidence Intervals
Semustine
Recurrence
Therapeutics
Rectal Neoplasms
Survival
Radiotherapy
Drug Therapy
Poisons
Leukopenia
Thrombocytopenia
Nausea
Vomiting
Diarrhea
Lymph Nodes
Neoplasm Metastasis
Mortality

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Krook, J. E., Moertel, C. G., Gunderson, L. L., Wieand, H. S., Collins, R. T., Beart, R. W., ... Vidyarthi, C. (1991). Effective surgical adjuvant therapy for high-risk rectal carcinoma. New England Journal of Medicine, 324(11), 709-715.

Effective surgical adjuvant therapy for high-risk rectal carcinoma. / Krook, J. E.; Moertel, C. G.; Gunderson, L. L.; Wieand, H. S.; Collins, R. T.; Beart, R. W.; Kubista, T. P.; Witzig, Thomas Elmer; Meyers, W. C.; Mailliard, J. A.; Twito, D. I.; Morton, R. F.; Veeder, M. H.; Witzig, T. E.; Cha, S.; Vidyarthi, C.

In: New England Journal of Medicine, Vol. 324, No. 11, 1991, p. 709-715.

Research output: Contribution to journalArticle

Krook, JE, Moertel, CG, Gunderson, LL, Wieand, HS, Collins, RT, Beart, RW, Kubista, TP, Witzig, TE, Meyers, WC, Mailliard, JA, Twito, DI, Morton, RF, Veeder, MH, Witzig, TE, Cha, S & Vidyarthi, C 1991, 'Effective surgical adjuvant therapy for high-risk rectal carcinoma', New England Journal of Medicine, vol. 324, no. 11, pp. 709-715.
Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. New England Journal of Medicine. 1991;324(11):709-715.
Krook, J. E. ; Moertel, C. G. ; Gunderson, L. L. ; Wieand, H. S. ; Collins, R. T. ; Beart, R. W. ; Kubista, T. P. ; Witzig, Thomas Elmer ; Meyers, W. C. ; Mailliard, J. A. ; Twito, D. I. ; Morton, R. F. ; Veeder, M. H. ; Witzig, T. E. ; Cha, S. ; Vidyarthi, C. / Effective surgical adjuvant therapy for high-risk rectal carcinoma. In: New England Journal of Medicine. 1991 ; Vol. 324, No. 11. pp. 709-715.
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abstract = "Background. Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival. In a previous study, combined radiation and chemotherapy improved survival significantly as compared with surgery alone, but not as compared with adjuvant radiation, which many regard as standard therapy. We designed a combination regimen to optimize the contribution of chemotherapy, decrease recurrence, and improve survival as compared with adjuvant radiation alone. Methods. Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were randomly assigned to postoperative radiation alone (4500 to 5040 cGy) or to radiation plus fluorouracil, which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine (methyl-CCNU). Results. After a median follow-up of more than seven years, the combined therapy had reduced the recurrence of rectal cancer by 34 percent (P = 0.0016; 95 percent confidence interval, 12 to 50 percent). Initial local recurrence was reduced by 46 percent (P = 0.036; 95 percent confidence interval, 2 to 70 percent), and distant metastasis by 37 percent (P = 0.011; 95 percent confidence interval, 9 to 57 percent). In addition, combined therapy reduced the rate of cancer-related deaths by 36 percent (P = 0.0071; 95 percent confidence interval, 14 to 53 percent) and the overall death rate by 29 percent (P = 0.025; 95 percent confidence interval, 7 to 45 percent). Its acute toxic effects included nausea, vomiting, diarrhea, leukopenia, and thrombocytopenia. These effects were seldom severe. Severe, delayed treatment-related reactions, usually small-bowel obstruction requiring surgery, occurred in 6.7 percent of all patients receiving radiation, and the frequencies of these complications were comparable in both treatment groups. Conclusions. The combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil-based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis as compared with postoperative radiation alone.",
author = "Krook, {J. E.} and Moertel, {C. G.} and Gunderson, {L. L.} and Wieand, {H. S.} and Collins, {R. T.} and Beart, {R. W.} and Kubista, {T. P.} and Witzig, {Thomas Elmer} and Meyers, {W. C.} and Mailliard, {J. A.} and Twito, {D. I.} and Morton, {R. F.} and Veeder, {M. H.} and Witzig, {T. E.} and S. Cha and C. Vidyarthi",
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T1 - Effective surgical adjuvant therapy for high-risk rectal carcinoma

AU - Krook, J. E.

AU - Moertel, C. G.

AU - Gunderson, L. L.

AU - Wieand, H. S.

AU - Collins, R. T.

AU - Beart, R. W.

AU - Kubista, T. P.

AU - Witzig, Thomas Elmer

AU - Meyers, W. C.

AU - Mailliard, J. A.

AU - Twito, D. I.

AU - Morton, R. F.

AU - Veeder, M. H.

AU - Witzig, T. E.

AU - Cha, S.

AU - Vidyarthi, C.

PY - 1991

Y1 - 1991

N2 - Background. Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival. In a previous study, combined radiation and chemotherapy improved survival significantly as compared with surgery alone, but not as compared with adjuvant radiation, which many regard as standard therapy. We designed a combination regimen to optimize the contribution of chemotherapy, decrease recurrence, and improve survival as compared with adjuvant radiation alone. Methods. Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were randomly assigned to postoperative radiation alone (4500 to 5040 cGy) or to radiation plus fluorouracil, which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine (methyl-CCNU). Results. After a median follow-up of more than seven years, the combined therapy had reduced the recurrence of rectal cancer by 34 percent (P = 0.0016; 95 percent confidence interval, 12 to 50 percent). Initial local recurrence was reduced by 46 percent (P = 0.036; 95 percent confidence interval, 2 to 70 percent), and distant metastasis by 37 percent (P = 0.011; 95 percent confidence interval, 9 to 57 percent). In addition, combined therapy reduced the rate of cancer-related deaths by 36 percent (P = 0.0071; 95 percent confidence interval, 14 to 53 percent) and the overall death rate by 29 percent (P = 0.025; 95 percent confidence interval, 7 to 45 percent). Its acute toxic effects included nausea, vomiting, diarrhea, leukopenia, and thrombocytopenia. These effects were seldom severe. Severe, delayed treatment-related reactions, usually small-bowel obstruction requiring surgery, occurred in 6.7 percent of all patients receiving radiation, and the frequencies of these complications were comparable in both treatment groups. Conclusions. The combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil-based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis as compared with postoperative radiation alone.

AB - Background. Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival. In a previous study, combined radiation and chemotherapy improved survival significantly as compared with surgery alone, but not as compared with adjuvant radiation, which many regard as standard therapy. We designed a combination regimen to optimize the contribution of chemotherapy, decrease recurrence, and improve survival as compared with adjuvant radiation alone. Methods. Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were randomly assigned to postoperative radiation alone (4500 to 5040 cGy) or to radiation plus fluorouracil, which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine (methyl-CCNU). Results. After a median follow-up of more than seven years, the combined therapy had reduced the recurrence of rectal cancer by 34 percent (P = 0.0016; 95 percent confidence interval, 12 to 50 percent). Initial local recurrence was reduced by 46 percent (P = 0.036; 95 percent confidence interval, 2 to 70 percent), and distant metastasis by 37 percent (P = 0.011; 95 percent confidence interval, 9 to 57 percent). In addition, combined therapy reduced the rate of cancer-related deaths by 36 percent (P = 0.0071; 95 percent confidence interval, 14 to 53 percent) and the overall death rate by 29 percent (P = 0.025; 95 percent confidence interval, 7 to 45 percent). Its acute toxic effects included nausea, vomiting, diarrhea, leukopenia, and thrombocytopenia. These effects were seldom severe. Severe, delayed treatment-related reactions, usually small-bowel obstruction requiring surgery, occurred in 6.7 percent of all patients receiving radiation, and the frequencies of these complications were comparable in both treatment groups. Conclusions. The combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil-based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis as compared with postoperative radiation alone.

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