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.

Abstract

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.

• Authors: Gilberto de Lima Lopes Jr, Alberto Chiappori, George Simon, Eric Haura, Dan Sullivan, Scott Antonia, Michel Langevin, Richard Lush, Caio Max Rocha-Lima
• Journal: Cancer (Cancer) Vol. 109 Issue 7 Pg. 1413-9 (Apr 01 2007) ISSN: 0008-543X [Print] United States
• PMID: 17326096 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2007 American Cancer Society.

Chemical References

• Deoxycytidine
• Irinotecan
• Carboplatin
• Camptothecin
• Gemcitabine

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Camptothecin (administration & dosage, analogs & derivatives)
• Carboplatin (administration & dosage)
• Carcinoma, Neuroendocrine (drug therapy)
• Carcinoma, Small Cell (drug therapy)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Feasibility Studies
• Female
• Humans
• Irinotecan
• Lung Neoplasms (drug therapy)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Staging
• Neoplasms (drug therapy)
• Gemcitabine