Phase II trial of irinotecan in patients with metastatic colorectal carcinoma

Henry Clement Pitot, Donald B. Wender, Michael J. O'Connell, Georgene Schroeder, Richard M. Goldberg, Joseph Rubin, James A. Mailliard, James A. Knost, Chirantan Ghosh, Ron J. Kirschling, Ralph Levitt, Harold E. Windschitl

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Abstract

Purpose: To evaluate the objective tumor response rate and toxicities of patients with metastatic colorectal carcinoma treated with irinotecan hydrochloride (CPT- 11). Patients and Methods: A total of 121 patients with advanced colorectal carcinoma-90 with prior fluorouracil (5-FU) exposure and 31 chemotherapeutically naive patients-were enrolled between May 1993 and June 1994. Patients were treated with CPT-11 at 125 mg/m2 intravenously weekly for 4 weeks followed by a 2-week rest. Results: Among 90 patients with prior 5-FU chemotherapy, 12 partial responses were observed (response rate, 13.3%; 95% confidence interval [CI], 7.1% to 22.1%). Among 31 chemotherapy- naive patients, eight had partial responses (response rate, 25.8%; 95% CI, 11 .9% to 44.6%). The median response duration as measured from time of initial treatment for the two groups was 7.7 months and 7.6 months, respectively. The major adverse reactions were gastrointestinal and hematologic. The incidence of grade 3 or 4 diarrhea was 36.4%, while the overall incidence of grade 3 or 4 leukopenia was 21.5% of patients. Only four of 121 patients (3.3%) developed neutropenic fever (grade 4 neutropenia with grade 2 fever). The incidence of grade 4 leukopenia was higher in patients with prior pelvic radiotherapy (χ2 test P = .04), while the incidence of grade 3 or 4 diarrhea demonstrated no association with previous pelvic irradiation. Conclusion: According to the study design, CPT-11 showed promising activity in chemotherapy-naive patients with advanced colorectal carcinoma and modest activity in patients with prior 5-FU exposure. The toxicity with this schedule appears manageable with appropriate dose modification for individual patient tolerance and an intensive loperamide regimen for the management of diarrhea. Care should be taken when treating patients with prior pelvic radiotherapy because of the increased risk of neutropenia.

Original languageEnglish (US)
Pages (from-to)2910-2919
Number of pages10
JournalJournal of Clinical Oncology
Volume15
Issue number8
StatePublished - Aug 1997

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irinotecan
Colorectal Neoplasms
Fluorouracil
Diarrhea
Incidence
Leukopenia
Neutropenia
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pitot, H. C., Wender, D. B., O'Connell, M. J., Schroeder, G., Goldberg, R. M., Rubin, J., ... Windschitl, H. E. (1997). Phase II trial of irinotecan in patients with metastatic colorectal carcinoma. Journal of Clinical Oncology, 15(8), 2910-2919.

Phase II trial of irinotecan in patients with metastatic colorectal carcinoma. / Pitot, Henry Clement; Wender, Donald B.; O'Connell, Michael J.; Schroeder, Georgene; Goldberg, Richard M.; Rubin, Joseph; Mailliard, James A.; Knost, James A.; Ghosh, Chirantan; Kirschling, Ron J.; Levitt, Ralph; Windschitl, Harold E.

In: Journal of Clinical Oncology, Vol. 15, No. 8, 08.1997, p. 2910-2919.

Research output: Contribution to journalArticle

Pitot, HC, Wender, DB, O'Connell, MJ, Schroeder, G, Goldberg, RM, Rubin, J, Mailliard, JA, Knost, JA, Ghosh, C, Kirschling, RJ, Levitt, R & Windschitl, HE 1997, 'Phase II trial of irinotecan in patients with metastatic colorectal carcinoma', Journal of Clinical Oncology, vol. 15, no. 8, pp. 2910-2919.
Pitot HC, Wender DB, O'Connell MJ, Schroeder G, Goldberg RM, Rubin J et al. Phase II trial of irinotecan in patients with metastatic colorectal carcinoma. Journal of Clinical Oncology. 1997 Aug;15(8):2910-2919.
Pitot, Henry Clement ; Wender, Donald B. ; O'Connell, Michael J. ; Schroeder, Georgene ; Goldberg, Richard M. ; Rubin, Joseph ; Mailliard, James A. ; Knost, James A. ; Ghosh, Chirantan ; Kirschling, Ron J. ; Levitt, Ralph ; Windschitl, Harold E. / Phase II trial of irinotecan in patients with metastatic colorectal carcinoma. In: Journal of Clinical Oncology. 1997 ; Vol. 15, No. 8. pp. 2910-2919.
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abstract = "Purpose: To evaluate the objective tumor response rate and toxicities of patients with metastatic colorectal carcinoma treated with irinotecan hydrochloride (CPT- 11). Patients and Methods: A total of 121 patients with advanced colorectal carcinoma-90 with prior fluorouracil (5-FU) exposure and 31 chemotherapeutically naive patients-were enrolled between May 1993 and June 1994. Patients were treated with CPT-11 at 125 mg/m2 intravenously weekly for 4 weeks followed by a 2-week rest. Results: Among 90 patients with prior 5-FU chemotherapy, 12 partial responses were observed (response rate, 13.3{\%}; 95{\%} confidence interval [CI], 7.1{\%} to 22.1{\%}). Among 31 chemotherapy- naive patients, eight had partial responses (response rate, 25.8{\%}; 95{\%} CI, 11 .9{\%} to 44.6{\%}). The median response duration as measured from time of initial treatment for the two groups was 7.7 months and 7.6 months, respectively. The major adverse reactions were gastrointestinal and hematologic. The incidence of grade 3 or 4 diarrhea was 36.4{\%}, while the overall incidence of grade 3 or 4 leukopenia was 21.5{\%} of patients. Only four of 121 patients (3.3{\%}) developed neutropenic fever (grade 4 neutropenia with grade 2 fever). The incidence of grade 4 leukopenia was higher in patients with prior pelvic radiotherapy (χ2 test P = .04), while the incidence of grade 3 or 4 diarrhea demonstrated no association with previous pelvic irradiation. Conclusion: According to the study design, CPT-11 showed promising activity in chemotherapy-naive patients with advanced colorectal carcinoma and modest activity in patients with prior 5-FU exposure. The toxicity with this schedule appears manageable with appropriate dose modification for individual patient tolerance and an intensive loperamide regimen for the management of diarrhea. Care should be taken when treating patients with prior pelvic radiotherapy because of the increased risk of neutropenia.",
author = "Pitot, {Henry Clement} and Wender, {Donald B.} and O'Connell, {Michael J.} and Georgene Schroeder and Goldberg, {Richard M.} and Joseph Rubin and Mailliard, {James A.} and Knost, {James A.} and Chirantan Ghosh and Kirschling, {Ron J.} and Ralph Levitt and Windschitl, {Harold E.}",
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AU - Wender, Donald B.

AU - O'Connell, Michael J.

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AU - Goldberg, Richard M.

AU - Rubin, Joseph

AU - Mailliard, James A.

AU - Knost, James A.

AU - Ghosh, Chirantan

AU - Kirschling, Ron J.

AU - Levitt, Ralph

AU - Windschitl, Harold E.

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N2 - Purpose: To evaluate the objective tumor response rate and toxicities of patients with metastatic colorectal carcinoma treated with irinotecan hydrochloride (CPT- 11). Patients and Methods: A total of 121 patients with advanced colorectal carcinoma-90 with prior fluorouracil (5-FU) exposure and 31 chemotherapeutically naive patients-were enrolled between May 1993 and June 1994. Patients were treated with CPT-11 at 125 mg/m2 intravenously weekly for 4 weeks followed by a 2-week rest. Results: Among 90 patients with prior 5-FU chemotherapy, 12 partial responses were observed (response rate, 13.3%; 95% confidence interval [CI], 7.1% to 22.1%). Among 31 chemotherapy- naive patients, eight had partial responses (response rate, 25.8%; 95% CI, 11 .9% to 44.6%). The median response duration as measured from time of initial treatment for the two groups was 7.7 months and 7.6 months, respectively. The major adverse reactions were gastrointestinal and hematologic. The incidence of grade 3 or 4 diarrhea was 36.4%, while the overall incidence of grade 3 or 4 leukopenia was 21.5% of patients. Only four of 121 patients (3.3%) developed neutropenic fever (grade 4 neutropenia with grade 2 fever). The incidence of grade 4 leukopenia was higher in patients with prior pelvic radiotherapy (χ2 test P = .04), while the incidence of grade 3 or 4 diarrhea demonstrated no association with previous pelvic irradiation. Conclusion: According to the study design, CPT-11 showed promising activity in chemotherapy-naive patients with advanced colorectal carcinoma and modest activity in patients with prior 5-FU exposure. The toxicity with this schedule appears manageable with appropriate dose modification for individual patient tolerance and an intensive loperamide regimen for the management of diarrhea. Care should be taken when treating patients with prior pelvic radiotherapy because of the increased risk of neutropenia.

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