Phase III randomized study to compare interferon alfa-2a in combination with fluorouracil versus fluorouracil alone in patients with advanced colorectal cancer

F. A. Greco, R. Figlin, M. York, Lawrence Einhorn, R. Schilsky, E. M. Marshall, S. S. Buys, M. J. Froimtchuk, J. Schuller, L. Schuchter, M. Buyse, L. Ritter, A. Man, A. K. Yap

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Abstract

Purpose: To compare the efficacy and toxicity profiles of a combination of fluorouracil (5-FU) and recombinant human interferon alfa-2a ([IFNα2a] Roferon-A; Hoffmann-LaRoche, Basel, Switzerland) versus 5-FU alone in the treatment of advanced colorectal cancer (ACC). Patients and Methods: A total of 245 previously untreated ACC patients were randomized to receive either IFNα2a (9 million IU) subcutaneously (SC) three times weekly with 5-FU (750 mg/m2/d) by continuous intravenous (CIV) infusion on days 1 to 5 and then, after a 1-week hiatus, as a weekly IV bolus at the same dose (IFN/5-FU), or 5-FU alone at the same dose schedule (5-FU). Results: There were no significant differences between IFN/5-FU and 5-FU alone in the overall response rate (24% v 17%, P = .2), duration of response (median, 6.4 v 8.1 months), time to response (plateau at 3 months), time to progressive disease ([PD] median, 4.8 v 4.9 months), or survival duration (median, 13.9 v 13.2 months). Toxicity profiles were not statistically different except for constitutional symptoms, which were more frequent and more severe with IFN/5- FU. More patients interrupted treatment for adverse events (AEs) with IFN/5- FU (34%) than with 5-FU alone (21%) (P = .03). The number of deaths (mostly unrelated to drug treatment) during the study (8%) was similar with both regimens. Conclusion: The combination IFN/5-FU produced a response rate, response duration, and survival duration similar to that of 5-FU alone. The addition of IFN to 5-FU in the doses and schedules used in this study did not provide any further benefit over 5-FU alone and cannot be recommended for patients with metastatic ACC. This study confirms the value of large prospective randomized clinical trials to determine the clinical value of regimens that emerge from smaller single-center phase II studies.

Original languageEnglish (US)
Pages (from-to)2674-2681
Number of pages8
JournalJournal of Clinical Oncology
Volume14
Issue number10
StatePublished - 1996
Externally publishedYes

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Fluorouracil
Colorectal Neoplasms
interferon alfa-2a
Appointments and Schedules
Survival
Switzerland
Intravenous Infusions
Therapeutics
Randomized Controlled Trials

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase III randomized study to compare interferon alfa-2a in combination with fluorouracil versus fluorouracil alone in patients with advanced colorectal cancer. / Greco, F. A.; Figlin, R.; York, M.; Einhorn, Lawrence; Schilsky, R.; Marshall, E. M.; Buys, S. S.; Froimtchuk, M. J.; Schuller, J.; Schuchter, L.; Buyse, M.; Ritter, L.; Man, A.; Yap, A. K.

In: Journal of Clinical Oncology, Vol. 14, No. 10, 1996, p. 2674-2681.

Research output: Contribution to journalArticle

Greco, FA, Figlin, R, York, M, Einhorn, L, Schilsky, R, Marshall, EM, Buys, SS, Froimtchuk, MJ, Schuller, J, Schuchter, L, Buyse, M, Ritter, L, Man, A & Yap, AK 1996, 'Phase III randomized study to compare interferon alfa-2a in combination with fluorouracil versus fluorouracil alone in patients with advanced colorectal cancer', Journal of Clinical Oncology, vol. 14, no. 10, pp. 2674-2681.
Greco, F. A. ; Figlin, R. ; York, M. ; Einhorn, Lawrence ; Schilsky, R. ; Marshall, E. M. ; Buys, S. S. ; Froimtchuk, M. J. ; Schuller, J. ; Schuchter, L. ; Buyse, M. ; Ritter, L. ; Man, A. ; Yap, A. K. / Phase III randomized study to compare interferon alfa-2a in combination with fluorouracil versus fluorouracil alone in patients with advanced colorectal cancer. In: Journal of Clinical Oncology. 1996 ; Vol. 14, No. 10. pp. 2674-2681.
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title = "Phase III randomized study to compare interferon alfa-2a in combination with fluorouracil versus fluorouracil alone in patients with advanced colorectal cancer",
abstract = "Purpose: To compare the efficacy and toxicity profiles of a combination of fluorouracil (5-FU) and recombinant human interferon alfa-2a ([IFNα2a] Roferon-A; Hoffmann-LaRoche, Basel, Switzerland) versus 5-FU alone in the treatment of advanced colorectal cancer (ACC). Patients and Methods: A total of 245 previously untreated ACC patients were randomized to receive either IFNα2a (9 million IU) subcutaneously (SC) three times weekly with 5-FU (750 mg/m2/d) by continuous intravenous (CIV) infusion on days 1 to 5 and then, after a 1-week hiatus, as a weekly IV bolus at the same dose (IFN/5-FU), or 5-FU alone at the same dose schedule (5-FU). Results: There were no significant differences between IFN/5-FU and 5-FU alone in the overall response rate (24{\%} v 17{\%}, P = .2), duration of response (median, 6.4 v 8.1 months), time to response (plateau at 3 months), time to progressive disease ([PD] median, 4.8 v 4.9 months), or survival duration (median, 13.9 v 13.2 months). Toxicity profiles were not statistically different except for constitutional symptoms, which were more frequent and more severe with IFN/5- FU. More patients interrupted treatment for adverse events (AEs) with IFN/5- FU (34{\%}) than with 5-FU alone (21{\%}) (P = .03). The number of deaths (mostly unrelated to drug treatment) during the study (8{\%}) was similar with both regimens. Conclusion: The combination IFN/5-FU produced a response rate, response duration, and survival duration similar to that of 5-FU alone. The addition of IFN to 5-FU in the doses and schedules used in this study did not provide any further benefit over 5-FU alone and cannot be recommended for patients with metastatic ACC. This study confirms the value of large prospective randomized clinical trials to determine the clinical value of regimens that emerge from smaller single-center phase II studies.",
author = "Greco, {F. A.} and R. Figlin and M. York and Lawrence Einhorn and R. Schilsky and Marshall, {E. M.} and Buys, {S. S.} and Froimtchuk, {M. J.} and J. Schuller and L. Schuchter and M. Buyse and L. Ritter and A. Man and Yap, {A. K.}",
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language = "English (US)",
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T1 - Phase III randomized study to compare interferon alfa-2a in combination with fluorouracil versus fluorouracil alone in patients with advanced colorectal cancer

AU - Greco, F. A.

AU - Figlin, R.

AU - York, M.

AU - Einhorn, Lawrence

AU - Schilsky, R.

AU - Marshall, E. M.

AU - Buys, S. S.

AU - Froimtchuk, M. J.

AU - Schuller, J.

AU - Schuchter, L.

AU - Buyse, M.

AU - Ritter, L.

AU - Man, A.

AU - Yap, A. K.

PY - 1996

Y1 - 1996

N2 - Purpose: To compare the efficacy and toxicity profiles of a combination of fluorouracil (5-FU) and recombinant human interferon alfa-2a ([IFNα2a] Roferon-A; Hoffmann-LaRoche, Basel, Switzerland) versus 5-FU alone in the treatment of advanced colorectal cancer (ACC). Patients and Methods: A total of 245 previously untreated ACC patients were randomized to receive either IFNα2a (9 million IU) subcutaneously (SC) three times weekly with 5-FU (750 mg/m2/d) by continuous intravenous (CIV) infusion on days 1 to 5 and then, after a 1-week hiatus, as a weekly IV bolus at the same dose (IFN/5-FU), or 5-FU alone at the same dose schedule (5-FU). Results: There were no significant differences between IFN/5-FU and 5-FU alone in the overall response rate (24% v 17%, P = .2), duration of response (median, 6.4 v 8.1 months), time to response (plateau at 3 months), time to progressive disease ([PD] median, 4.8 v 4.9 months), or survival duration (median, 13.9 v 13.2 months). Toxicity profiles were not statistically different except for constitutional symptoms, which were more frequent and more severe with IFN/5- FU. More patients interrupted treatment for adverse events (AEs) with IFN/5- FU (34%) than with 5-FU alone (21%) (P = .03). The number of deaths (mostly unrelated to drug treatment) during the study (8%) was similar with both regimens. Conclusion: The combination IFN/5-FU produced a response rate, response duration, and survival duration similar to that of 5-FU alone. The addition of IFN to 5-FU in the doses and schedules used in this study did not provide any further benefit over 5-FU alone and cannot be recommended for patients with metastatic ACC. This study confirms the value of large prospective randomized clinical trials to determine the clinical value of regimens that emerge from smaller single-center phase II studies.

AB - Purpose: To compare the efficacy and toxicity profiles of a combination of fluorouracil (5-FU) and recombinant human interferon alfa-2a ([IFNα2a] Roferon-A; Hoffmann-LaRoche, Basel, Switzerland) versus 5-FU alone in the treatment of advanced colorectal cancer (ACC). Patients and Methods: A total of 245 previously untreated ACC patients were randomized to receive either IFNα2a (9 million IU) subcutaneously (SC) three times weekly with 5-FU (750 mg/m2/d) by continuous intravenous (CIV) infusion on days 1 to 5 and then, after a 1-week hiatus, as a weekly IV bolus at the same dose (IFN/5-FU), or 5-FU alone at the same dose schedule (5-FU). Results: There were no significant differences between IFN/5-FU and 5-FU alone in the overall response rate (24% v 17%, P = .2), duration of response (median, 6.4 v 8.1 months), time to response (plateau at 3 months), time to progressive disease ([PD] median, 4.8 v 4.9 months), or survival duration (median, 13.9 v 13.2 months). Toxicity profiles were not statistically different except for constitutional symptoms, which were more frequent and more severe with IFN/5- FU. More patients interrupted treatment for adverse events (AEs) with IFN/5- FU (34%) than with 5-FU alone (21%) (P = .03). The number of deaths (mostly unrelated to drug treatment) during the study (8%) was similar with both regimens. Conclusion: The combination IFN/5-FU produced a response rate, response duration, and survival duration similar to that of 5-FU alone. The addition of IFN to 5-FU in the doses and schedules used in this study did not provide any further benefit over 5-FU alone and cannot be recommended for patients with metastatic ACC. This study confirms the value of large prospective randomized clinical trials to determine the clinical value of regimens that emerge from smaller single-center phase II studies.

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