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 language | English |
|---|---|
| Pages (from-to) | 127-133 |
| Number of pages | 7 |
| Journal | Oncology |
| Volume | 60 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2001 |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=17744391551&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17744391551&partnerID=8YFLogxK
U2 - 10.1159/000055309
DO - 10.1159/000055309
M3 - Article
VL - 60
SP - 127
EP - 133
JO - Oncology
JF - Oncology
SN - 0030-2414
IS - 2
ER -