TY - JOUR
T1 - Phase I study of carboplatin in combination with gemcitabine and irinotecan in patients with solid tumors
T2 - Preliminary evidence of activity in small cell and neuroendocrine carcinomas
AU - Lopes, Gilberto De Lima
AU - Chiappori, Alberto
AU - Simon, George
AU - Haura, Eric
AU - Sullivan, Dan
AU - Antonia, Scott
AU - Langevin, Michel
AU - Lush, Richard
AU - Rocha-Lima, Caio Max
PY - 2007/4/1
Y1 - 2007/4/1
N2 - BACKGROUND. The objective of this study was to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of carboplatin in combination with gemcitabine and irinotecan in patients with solid tumors. METHODS. Patients with solid tumors who were not candidates for standard chemotherapy received escalating doses of carboplatin, gemcitabine, and irinotecan. RESULTS. Twenty-eight patients were enrolled. Two of 4 patients who received carboplatin at an area under the curve (AUC) of 5 on Day 1 with gemcitabine 800 mg/m 2 and irinotecan 80 mg/m2 on Days 1 and 8 developed DLT, along with 2 of 12 patients at the immediate-lower dose level: carboplatin at an AUC of 4 on Day 1 with gemcitabine 800 mg/m2 and irinotecan 80 mg/m2 on Days 1 and 8. In an attempt to improve drug delivery on Day 8, a different schedule was studied. Carboplatin at an AUC of 2, gemcitabine 800 mg/m2, and irinotecan 60 mg/m2, all given on Days 1 and 8, was explored in 12 patients. Two patients were unable to receive therapy on Day 8. Twenty-four patients developed grade 3 or 4 hematologic toxicity. Nonhematologic side effects were mostly mild and reversible with the exception of 1 patient, who developed acute liver failure after the fourth cycle of chemotherapy and died. Objective responses were observed in 7 patients, including 5 patients who had small cell and neuroendocrine carcinomas. CONCLUSIONS. Carboplatin in combination with gemcitabine and irinotecan was feasible. However, compromise of single-agent doses of all 3 drugs was necessary because of toxicity. Additional studies are warranted in patients with small cell and high-grade neuroendocrine carcinomas.
AB - BACKGROUND. The objective of this study was to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of carboplatin in combination with gemcitabine and irinotecan in patients with solid tumors. METHODS. Patients with solid tumors who were not candidates for standard chemotherapy received escalating doses of carboplatin, gemcitabine, and irinotecan. RESULTS. Twenty-eight patients were enrolled. Two of 4 patients who received carboplatin at an area under the curve (AUC) of 5 on Day 1 with gemcitabine 800 mg/m 2 and irinotecan 80 mg/m2 on Days 1 and 8 developed DLT, along with 2 of 12 patients at the immediate-lower dose level: carboplatin at an AUC of 4 on Day 1 with gemcitabine 800 mg/m2 and irinotecan 80 mg/m2 on Days 1 and 8. In an attempt to improve drug delivery on Day 8, a different schedule was studied. Carboplatin at an AUC of 2, gemcitabine 800 mg/m2, and irinotecan 60 mg/m2, all given on Days 1 and 8, was explored in 12 patients. Two patients were unable to receive therapy on Day 8. Twenty-four patients developed grade 3 or 4 hematologic toxicity. Nonhematologic side effects were mostly mild and reversible with the exception of 1 patient, who developed acute liver failure after the fourth cycle of chemotherapy and died. Objective responses were observed in 7 patients, including 5 patients who had small cell and neuroendocrine carcinomas. CONCLUSIONS. Carboplatin in combination with gemcitabine and irinotecan was feasible. However, compromise of single-agent doses of all 3 drugs was necessary because of toxicity. Additional studies are warranted in patients with small cell and high-grade neuroendocrine carcinomas.
KW - Carboplatin
KW - Gemcitabine
KW - Irinotecan
KW - Neuroendocrine
KW - Phase I
KW - Small cell lung cancer
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U2 - 10.1002/cncr.22522
DO - 10.1002/cncr.22522
M3 - Article
C2 - 17326096
AN - SCOPUS:33947511117
VL - 109
SP - 1413
EP - 1419
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 7
ER -