Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma

Jean L Grem, E. Jordan, M. E. Robson, R. A. Binder, J. M. Hamilton, S. M. Steinberg, S. G. Arbuck, R. A. Beveridge, A. N. Kales, J. A. Miller, R. B. Weiss, N. McAtee, A. Chen, B. Goldspiel, E. Sover, C. J. Allegra

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Purpose: To test the activity of a regimen of interferon alfa-2a (IFN α- 2a) 5 x 106 U/m2 subcutaneously (SC) days 1 through 7 combined with leucovorin 500 mg/m2/d intravenously (IV) over 30 minutes and fluorouracil (5-FU) 370 mg/m2/d through IV push 1 hour after leucovorin days 2 through 6 in a phase II study. Patients and Methods: Forty-six patients with a good performance status (PS) with measurable colorectal cancer and no prior therapy for metastatic disease were entered. Cycles were repeated at 3-week intervals if toxicity had resolved. The 5-FU dose was increased by 15% if toxicity was mild, and decreased by 15% for grade 3 to 4 nonhematologic or grade 4 hematologic toxicity. Results: Three complete responses (CRs) and 21 partial responses (PRs) were seen among 44 assessable patients (54%; 95% confidence interval, 39% to 70%). A moderately strong association was noted between PS and response: PS 0 (n = 26), two CRs and 15 PRs (65%); PS 1 (n = 13), one CR and six PRs (54%); PS 2 (n = 5), zero CRs and zero PRs (0%; two- tailed P = .026). With a median follow-up duration of 18.8 months, the median time to treatment failure (TTF) and survival were 7.8 months and 16.3 months, respectively. Doses were escalated to 425 mg/m2/d 5-FU in 10 patients, but only four tolerated the higher dose. When expressed as the most severe degree of toxicity experienced by each patient across all cycles, grade 3 to 4 toxicity of the following types was observed; mucositis, 37%; diarrhea, 40%; rash, 7%; fatigue, 14%; granulocytopenia, 13%. Dose-limiting toxicity at 370 mg/m2/d 5-FU eventually occurred in 28 patients (61%). Twelve patients (26%) required an IFN α-2a dose reduction for constitutional toxicity. Conclusion: This regimen has promising activity in advanced colorectal cancer, particularly in patients with an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1.

Original languageEnglish (US)
Pages (from-to)1737-1745
Number of pages9
JournalJournal of Clinical Oncology
Volume11
Issue number9
DOIs
StatePublished - Jan 1 1993

Fingerprint

Leucovorin
Fluorouracil
Colorectal Neoplasms
Mucositis
Agranulocytosis
interferon alfa-2a
Exanthema
Treatment Failure
Interferon-alpha
Fatigue
Diarrhea
Confidence Intervals
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Grem, J. L., Jordan, E., Robson, M. E., Binder, R. A., Hamilton, J. M., Steinberg, S. M., ... Allegra, C. J. (1993). Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma. Journal of Clinical Oncology, 11(9), 1737-1745. https://doi.org/10.1200/JCO.1993.11.9.1737

Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma. / Grem, Jean L; Jordan, E.; Robson, M. E.; Binder, R. A.; Hamilton, J. M.; Steinberg, S. M.; Arbuck, S. G.; Beveridge, R. A.; Kales, A. N.; Miller, J. A.; Weiss, R. B.; McAtee, N.; Chen, A.; Goldspiel, B.; Sover, E.; Allegra, C. J.

In: Journal of Clinical Oncology, Vol. 11, No. 9, 01.01.1993, p. 1737-1745.

Research output: Contribution to journalArticle

Grem, JL, Jordan, E, Robson, ME, Binder, RA, Hamilton, JM, Steinberg, SM, Arbuck, SG, Beveridge, RA, Kales, AN, Miller, JA, Weiss, RB, McAtee, N, Chen, A, Goldspiel, B, Sover, E & Allegra, CJ 1993, 'Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma', Journal of Clinical Oncology, vol. 11, no. 9, pp. 1737-1745. https://doi.org/10.1200/JCO.1993.11.9.1737
Grem, Jean L ; Jordan, E. ; Robson, M. E. ; Binder, R. A. ; Hamilton, J. M. ; Steinberg, S. M. ; Arbuck, S. G. ; Beveridge, R. A. ; Kales, A. N. ; Miller, J. A. ; Weiss, R. B. ; McAtee, N. ; Chen, A. ; Goldspiel, B. ; Sover, E. ; Allegra, C. J. / Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma. In: Journal of Clinical Oncology. 1993 ; Vol. 11, No. 9. pp. 1737-1745.
@article{a7117c1180e54851896cc82476345b1b,
title = "Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma",
abstract = "Purpose: To test the activity of a regimen of interferon alfa-2a (IFN α- 2a) 5 x 106 U/m2 subcutaneously (SC) days 1 through 7 combined with leucovorin 500 mg/m2/d intravenously (IV) over 30 minutes and fluorouracil (5-FU) 370 mg/m2/d through IV push 1 hour after leucovorin days 2 through 6 in a phase II study. Patients and Methods: Forty-six patients with a good performance status (PS) with measurable colorectal cancer and no prior therapy for metastatic disease were entered. Cycles were repeated at 3-week intervals if toxicity had resolved. The 5-FU dose was increased by 15{\%} if toxicity was mild, and decreased by 15{\%} for grade 3 to 4 nonhematologic or grade 4 hematologic toxicity. Results: Three complete responses (CRs) and 21 partial responses (PRs) were seen among 44 assessable patients (54{\%}; 95{\%} confidence interval, 39{\%} to 70{\%}). A moderately strong association was noted between PS and response: PS 0 (n = 26), two CRs and 15 PRs (65{\%}); PS 1 (n = 13), one CR and six PRs (54{\%}); PS 2 (n = 5), zero CRs and zero PRs (0{\%}; two- tailed P = .026). With a median follow-up duration of 18.8 months, the median time to treatment failure (TTF) and survival were 7.8 months and 16.3 months, respectively. Doses were escalated to 425 mg/m2/d 5-FU in 10 patients, but only four tolerated the higher dose. When expressed as the most severe degree of toxicity experienced by each patient across all cycles, grade 3 to 4 toxicity of the following types was observed; mucositis, 37{\%}; diarrhea, 40{\%}; rash, 7{\%}; fatigue, 14{\%}; granulocytopenia, 13{\%}. Dose-limiting toxicity at 370 mg/m2/d 5-FU eventually occurred in 28 patients (61{\%}). Twelve patients (26{\%}) required an IFN α-2a dose reduction for constitutional toxicity. Conclusion: This regimen has promising activity in advanced colorectal cancer, particularly in patients with an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1.",
author = "Grem, {Jean L} and E. Jordan and Robson, {M. E.} and Binder, {R. A.} and Hamilton, {J. M.} and Steinberg, {S. M.} and Arbuck, {S. G.} and Beveridge, {R. A.} and Kales, {A. N.} and Miller, {J. A.} and Weiss, {R. B.} and N. McAtee and A. Chen and B. Goldspiel and E. Sover and Allegra, {C. J.}",
year = "1993",
month = "1",
day = "1",
doi = "10.1200/JCO.1993.11.9.1737",
language = "English (US)",
volume = "11",
pages = "1737--1745",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "9",

}

TY - JOUR

T1 - Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma

AU - Grem, Jean L

AU - Jordan, E.

AU - Robson, M. E.

AU - Binder, R. A.

AU - Hamilton, J. M.

AU - Steinberg, S. M.

AU - Arbuck, S. G.

AU - Beveridge, R. A.

AU - Kales, A. N.

AU - Miller, J. A.

AU - Weiss, R. B.

AU - McAtee, N.

AU - Chen, A.

AU - Goldspiel, B.

AU - Sover, E.

AU - Allegra, C. J.

PY - 1993/1/1

Y1 - 1993/1/1

N2 - Purpose: To test the activity of a regimen of interferon alfa-2a (IFN α- 2a) 5 x 106 U/m2 subcutaneously (SC) days 1 through 7 combined with leucovorin 500 mg/m2/d intravenously (IV) over 30 minutes and fluorouracil (5-FU) 370 mg/m2/d through IV push 1 hour after leucovorin days 2 through 6 in a phase II study. Patients and Methods: Forty-six patients with a good performance status (PS) with measurable colorectal cancer and no prior therapy for metastatic disease were entered. Cycles were repeated at 3-week intervals if toxicity had resolved. The 5-FU dose was increased by 15% if toxicity was mild, and decreased by 15% for grade 3 to 4 nonhematologic or grade 4 hematologic toxicity. Results: Three complete responses (CRs) and 21 partial responses (PRs) were seen among 44 assessable patients (54%; 95% confidence interval, 39% to 70%). A moderately strong association was noted between PS and response: PS 0 (n = 26), two CRs and 15 PRs (65%); PS 1 (n = 13), one CR and six PRs (54%); PS 2 (n = 5), zero CRs and zero PRs (0%; two- tailed P = .026). With a median follow-up duration of 18.8 months, the median time to treatment failure (TTF) and survival were 7.8 months and 16.3 months, respectively. Doses were escalated to 425 mg/m2/d 5-FU in 10 patients, but only four tolerated the higher dose. When expressed as the most severe degree of toxicity experienced by each patient across all cycles, grade 3 to 4 toxicity of the following types was observed; mucositis, 37%; diarrhea, 40%; rash, 7%; fatigue, 14%; granulocytopenia, 13%. Dose-limiting toxicity at 370 mg/m2/d 5-FU eventually occurred in 28 patients (61%). Twelve patients (26%) required an IFN α-2a dose reduction for constitutional toxicity. Conclusion: This regimen has promising activity in advanced colorectal cancer, particularly in patients with an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1.

AB - Purpose: To test the activity of a regimen of interferon alfa-2a (IFN α- 2a) 5 x 106 U/m2 subcutaneously (SC) days 1 through 7 combined with leucovorin 500 mg/m2/d intravenously (IV) over 30 minutes and fluorouracil (5-FU) 370 mg/m2/d through IV push 1 hour after leucovorin days 2 through 6 in a phase II study. Patients and Methods: Forty-six patients with a good performance status (PS) with measurable colorectal cancer and no prior therapy for metastatic disease were entered. Cycles were repeated at 3-week intervals if toxicity had resolved. The 5-FU dose was increased by 15% if toxicity was mild, and decreased by 15% for grade 3 to 4 nonhematologic or grade 4 hematologic toxicity. Results: Three complete responses (CRs) and 21 partial responses (PRs) were seen among 44 assessable patients (54%; 95% confidence interval, 39% to 70%). A moderately strong association was noted between PS and response: PS 0 (n = 26), two CRs and 15 PRs (65%); PS 1 (n = 13), one CR and six PRs (54%); PS 2 (n = 5), zero CRs and zero PRs (0%; two- tailed P = .026). With a median follow-up duration of 18.8 months, the median time to treatment failure (TTF) and survival were 7.8 months and 16.3 months, respectively. Doses were escalated to 425 mg/m2/d 5-FU in 10 patients, but only four tolerated the higher dose. When expressed as the most severe degree of toxicity experienced by each patient across all cycles, grade 3 to 4 toxicity of the following types was observed; mucositis, 37%; diarrhea, 40%; rash, 7%; fatigue, 14%; granulocytopenia, 13%. Dose-limiting toxicity at 370 mg/m2/d 5-FU eventually occurred in 28 patients (61%). Twelve patients (26%) required an IFN α-2a dose reduction for constitutional toxicity. Conclusion: This regimen has promising activity in advanced colorectal cancer, particularly in patients with an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1.

UR - http://www.scopus.com/inward/record.url?scp=0027326441&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027326441&partnerID=8YFLogxK

U2 - 10.1200/JCO.1993.11.9.1737

DO - 10.1200/JCO.1993.11.9.1737

M3 - Article

VL - 11

SP - 1737

EP - 1745

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 9

ER -