Irinotecan and mitomycin C in 5-fluorouracil-refractory colorectal cancer patients

A phase I/II study of the Southern Italy Cooperative Oncology Group

Pasquale Comella, Maria Biglietto, Rossana Casaretti, Luigi De Lucia, Antonio Avallone, Luigi Maiorino, Liberato Di Lullo, Giuseppe De Cataldis, Flavia Rivellini, Giuseppe Comella

Research output: Contribution to journalArticle

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Abstract

Purpose: To define the maximum tolerated dose (MTD) of irinotecan (CPT-11) given on days 1 and 8 with mitomycin C (MMC) given on day 1 in a monthly cycle, and to assess the toxicity and activity of this regimen in patients with previously treated colorectal carcinoma. Methods: Fifty-two patients, all pretreated with adjuvant 5-fluorouracil (20 patients) and/or one (35 patients) or two (8 patients) lines of chemotherapy, were entered in this study. Escalating doses of CPT-11 (starting from 150 mg/m 2) were administered on days 1 and 8, with escalating doses of MMC (starting from 8 mg/m 2) given on day 1, recycling every 28 days. At least 3 patients were treated at each dose level. Escalation proceeded unless 2 out of 3 or 4 out of 6 patients experienced a dose-limiting toxicity (DLT) after the first cycle. Results: Twelve patients were entered in the phase I study, and 4 consecutive dose levels were tested. At the last dose level (CPT-11 200 mg/m 2 plus MMC 10 mg/m 2) 4 of 6 patients experienced a DLT (i.e., grade 4 neutropenia in 2 patients and grade 3 diarrhea in 2 patients). Therefore, this dose level was considered as the MTD. Forty patients were treated at the previous dose level (CPT-11, 175 mg/m 2 plus MMC 10 mg/ m 2). One complete, 4 partial, 3 minor responses and 11 cases of stable disease were registered, giving a response rate of 12% [95% confidence interval (CI), 4-27%] and an overall control of tumor growth in 47% (95% CI, 31-64%) of patients. The median time to treatment failure was 6 months (range 1-19+). The median survival time was 14.5 months, and the 1-year and 2-year probability of survival were 56 and 43%. Neutropenia and diarrhea affected 62 and 58% of patients, grade 3 or 4 being registered in 26 and 23% of them, respectively. One episode of neutropenic fever was reported. Other acute toxicities were usually mild and manageable. Conclusions: CPT-11 175 mg/m 2 on days 1 and 8 associated with MMC 10 mg/m 2 on day 1, every 4 weeks, is a safe and moderately active regimen in heavily pretreated patients with advanced colorectal carcinoma. The role of MMC in this combination is doubtful, and further attempts with other new agents should be made to improve the outcome in these patients.

Original languageEnglish
Pages (from-to)127-133
Number of pages7
JournalOncology
Volume60
Issue number2
DOIs
Publication statusPublished - 2001

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irinotecan
Mitomycin
Fluorouracil
Italy
Colorectal Neoplasms
Maximum Tolerated Dose
Neutropenia

Keywords

  • Chemotherapy, salvage
  • Colorectal cancer
  • Irinotecan
  • Mitomycin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Irinotecan and mitomycin C in 5-fluorouracil-refractory colorectal cancer patients : A phase I/II study of the Southern Italy Cooperative Oncology Group. / Comella, Pasquale; Biglietto, Maria; Casaretti, Rossana; De Lucia, Luigi; Avallone, Antonio; Maiorino, Luigi; Di Lullo, Liberato; De Cataldis, Giuseppe; Rivellini, Flavia; Comella, Giuseppe.

In: Oncology, Vol. 60, No. 2, 2001, p. 127-133.

Research output: Contribution to journalArticle

Comella, P, Biglietto, M, Casaretti, R, De Lucia, L, Avallone, A, Maiorino, L, Di Lullo, L, De Cataldis, G, Rivellini, F & Comella, G 2001, 'Irinotecan and mitomycin C in 5-fluorouracil-refractory colorectal cancer patients: A phase I/II study of the Southern Italy Cooperative Oncology Group', Oncology, vol. 60, no. 2, pp. 127-133. https://doi.org/10.1159/000055309
Comella, Pasquale ; Biglietto, Maria ; Casaretti, Rossana ; De Lucia, Luigi ; Avallone, Antonio ; Maiorino, Luigi ; Di Lullo, Liberato ; De Cataldis, Giuseppe ; Rivellini, Flavia ; Comella, Giuseppe. / Irinotecan and mitomycin C in 5-fluorouracil-refractory colorectal cancer patients : A phase I/II study of the Southern Italy Cooperative Oncology Group. In: Oncology. 2001 ; Vol. 60, No. 2. pp. 127-133.
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title = "Irinotecan and mitomycin C in 5-fluorouracil-refractory colorectal cancer patients: A phase I/II study of the Southern Italy Cooperative Oncology Group",
abstract = "Purpose: To define the maximum tolerated dose (MTD) of irinotecan (CPT-11) given on days 1 and 8 with mitomycin C (MMC) given on day 1 in a monthly cycle, and to assess the toxicity and activity of this regimen in patients with previously treated colorectal carcinoma. Methods: Fifty-two patients, all pretreated with adjuvant 5-fluorouracil (20 patients) and/or one (35 patients) or two (8 patients) lines of chemotherapy, were entered in this study. Escalating doses of CPT-11 (starting from 150 mg/m 2) were administered on days 1 and 8, with escalating doses of MMC (starting from 8 mg/m 2) given on day 1, recycling every 28 days. At least 3 patients were treated at each dose level. Escalation proceeded unless 2 out of 3 or 4 out of 6 patients experienced a dose-limiting toxicity (DLT) after the first cycle. Results: Twelve patients were entered in the phase I study, and 4 consecutive dose levels were tested. At the last dose level (CPT-11 200 mg/m 2 plus MMC 10 mg/m 2) 4 of 6 patients experienced a DLT (i.e., grade 4 neutropenia in 2 patients and grade 3 diarrhea in 2 patients). Therefore, this dose level was considered as the MTD. Forty patients were treated at the previous dose level (CPT-11, 175 mg/m 2 plus MMC 10 mg/ m 2). One complete, 4 partial, 3 minor responses and 11 cases of stable disease were registered, giving a response rate of 12{\%} [95{\%} confidence interval (CI), 4-27{\%}] and an overall control of tumor growth in 47{\%} (95{\%} CI, 31-64{\%}) of patients. The median time to treatment failure was 6 months (range 1-19+). The median survival time was 14.5 months, and the 1-year and 2-year probability of survival were 56 and 43{\%}. Neutropenia and diarrhea affected 62 and 58{\%} of patients, grade 3 or 4 being registered in 26 and 23{\%} of them, respectively. One episode of neutropenic fever was reported. Other acute toxicities were usually mild and manageable. Conclusions: CPT-11 175 mg/m 2 on days 1 and 8 associated with MMC 10 mg/m 2 on day 1, every 4 weeks, is a safe and moderately active regimen in heavily pretreated patients with advanced colorectal carcinoma. The role of MMC in this combination is doubtful, and further attempts with other new agents should be made to improve the outcome in these patients.",
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author = "Pasquale Comella and Maria Biglietto and Rossana Casaretti and {De Lucia}, Luigi and Antonio Avallone and Luigi Maiorino and {Di Lullo}, Liberato and {De Cataldis}, Giuseppe and Flavia Rivellini and Giuseppe Comella",
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T1 - Irinotecan and mitomycin C in 5-fluorouracil-refractory colorectal cancer patients

T2 - A phase I/II study of the Southern Italy Cooperative Oncology Group

AU - Comella, Pasquale

AU - Biglietto, Maria

AU - Casaretti, Rossana

AU - De Lucia, Luigi

AU - Avallone, Antonio

AU - Maiorino, Luigi

AU - Di Lullo, Liberato

AU - De Cataldis, Giuseppe

AU - Rivellini, Flavia

AU - Comella, Giuseppe

PY - 2001

Y1 - 2001

N2 - Purpose: To define the maximum tolerated dose (MTD) of irinotecan (CPT-11) given on days 1 and 8 with mitomycin C (MMC) given on day 1 in a monthly cycle, and to assess the toxicity and activity of this regimen in patients with previously treated colorectal carcinoma. Methods: Fifty-two patients, all pretreated with adjuvant 5-fluorouracil (20 patients) and/or one (35 patients) or two (8 patients) lines of chemotherapy, were entered in this study. Escalating doses of CPT-11 (starting from 150 mg/m 2) were administered on days 1 and 8, with escalating doses of MMC (starting from 8 mg/m 2) given on day 1, recycling every 28 days. At least 3 patients were treated at each dose level. Escalation proceeded unless 2 out of 3 or 4 out of 6 patients experienced a dose-limiting toxicity (DLT) after the first cycle. Results: Twelve patients were entered in the phase I study, and 4 consecutive dose levels were tested. At the last dose level (CPT-11 200 mg/m 2 plus MMC 10 mg/m 2) 4 of 6 patients experienced a DLT (i.e., grade 4 neutropenia in 2 patients and grade 3 diarrhea in 2 patients). Therefore, this dose level was considered as the MTD. Forty patients were treated at the previous dose level (CPT-11, 175 mg/m 2 plus MMC 10 mg/ m 2). One complete, 4 partial, 3 minor responses and 11 cases of stable disease were registered, giving a response rate of 12% [95% confidence interval (CI), 4-27%] and an overall control of tumor growth in 47% (95% CI, 31-64%) of patients. The median time to treatment failure was 6 months (range 1-19+). The median survival time was 14.5 months, and the 1-year and 2-year probability of survival were 56 and 43%. Neutropenia and diarrhea affected 62 and 58% of patients, grade 3 or 4 being registered in 26 and 23% of them, respectively. One episode of neutropenic fever was reported. Other acute toxicities were usually mild and manageable. Conclusions: CPT-11 175 mg/m 2 on days 1 and 8 associated with MMC 10 mg/m 2 on day 1, every 4 weeks, is a safe and moderately active regimen in heavily pretreated patients with advanced colorectal carcinoma. The role of MMC in this combination is doubtful, and further attempts with other new agents should be made to improve the outcome in these patients.

AB - Purpose: To define the maximum tolerated dose (MTD) of irinotecan (CPT-11) given on days 1 and 8 with mitomycin C (MMC) given on day 1 in a monthly cycle, and to assess the toxicity and activity of this regimen in patients with previously treated colorectal carcinoma. Methods: Fifty-two patients, all pretreated with adjuvant 5-fluorouracil (20 patients) and/or one (35 patients) or two (8 patients) lines of chemotherapy, were entered in this study. Escalating doses of CPT-11 (starting from 150 mg/m 2) were administered on days 1 and 8, with escalating doses of MMC (starting from 8 mg/m 2) given on day 1, recycling every 28 days. At least 3 patients were treated at each dose level. Escalation proceeded unless 2 out of 3 or 4 out of 6 patients experienced a dose-limiting toxicity (DLT) after the first cycle. Results: Twelve patients were entered in the phase I study, and 4 consecutive dose levels were tested. At the last dose level (CPT-11 200 mg/m 2 plus MMC 10 mg/m 2) 4 of 6 patients experienced a DLT (i.e., grade 4 neutropenia in 2 patients and grade 3 diarrhea in 2 patients). Therefore, this dose level was considered as the MTD. Forty patients were treated at the previous dose level (CPT-11, 175 mg/m 2 plus MMC 10 mg/ m 2). One complete, 4 partial, 3 minor responses and 11 cases of stable disease were registered, giving a response rate of 12% [95% confidence interval (CI), 4-27%] and an overall control of tumor growth in 47% (95% CI, 31-64%) of patients. The median time to treatment failure was 6 months (range 1-19+). The median survival time was 14.5 months, and the 1-year and 2-year probability of survival were 56 and 43%. Neutropenia and diarrhea affected 62 and 58% of patients, grade 3 or 4 being registered in 26 and 23% of them, respectively. One episode of neutropenic fever was reported. Other acute toxicities were usually mild and manageable. Conclusions: CPT-11 175 mg/m 2 on days 1 and 8 associated with MMC 10 mg/m 2 on day 1, every 4 weeks, is a safe and moderately active regimen in heavily pretreated patients with advanced colorectal carcinoma. The role of MMC in this combination is doubtful, and further attempts with other new agents should be made to improve the outcome in these patients.

KW - Chemotherapy, salvage

KW - Colorectal cancer

KW - Irinotecan

KW - Mitomycin

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