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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.Patients with solid tumors who were not candidates for standard chemotherapy received escalating doses of carboplatin, gemcitabine, and irinotecan.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/m2 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.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. Cancer 2007. © 2007 American Cancer Society. [ABSTRACT FROM AUTHOR]