Phase I studies of gemcitabine combined with carboplatin or paclitaxel.
Gemcitabine is a novel nucleoside analogue with a unique mechanism of action. In light of its good single-agent activity in several solid tumors, generally mild toxicity profile, and potential for synergy, combination phase I studies with other active chemotherapeutic agents have been conducted. In two studies the combination of gemcitabine and carboplatin was used to treat patients with non-small cell lung cancer. Gemcitabine was administered weekly x 3 every 4 weeks, and carboplatin was given on day 1. Although dose-limiting myelotoxicity was observed, encouraging activity was noted. In other studies patients with recurrent or persistent ovarian cancer or with refractory solid tumors were treated with weekly gemcitabine and paclitaxel on a 28-day schedule or with both drugs given every 2 weeks. Dose escalation was possible and toxicities were manageable. The effect of sequence of drug administration on the toxicity profile was also examined. Further trials to establish the efficacy of these promising approaches as well as combinations of all three drugs are needed.
Pedersen
A G
AG
Eli Lilly Research Center Limited, Windlesham, UK.
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D016190:Carboplatin; D012264:Ribonucleotide Reductases; D017239:Paclitaxel; D000093542:Gemcitabine