Phase I study of carboplatin in combination with gemcitabine and irinotecan in patients with solid tumors: preliminary evidence of activity in small cell and neuroendocrine carcinomas.
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/m(2) 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/m(2) and irinotecan 80 mg/m(2) 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/m(2), and irinotecan 60 mg/m(2), 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.
de Lima Lopes
Gilberto
G
Department of Oncology, Johns Hopkins Singapore International Medical Center, Singapore.
Chiappori
Alberto
A
Simon
George
G
Haura
Eric
E
Sullivan
Dan
D
Antonia
Scott
S
Langevin
Michel
M
Lush
Richard
R
Rocha-Lima
Caio Max
CM
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
D003841:Deoxycytidine; D000077146:Irinotecan; D016190:Carboplatin; D002166:Camptothecin; D000093542:Gemcitabine