Gemcitabine and carboplatin in combination: phase I and phase II studies.
Gemcitabine has demonstrated single-agent activity in advanced, incurable non-small cell lung cancer, yielding response rates of > or =20%, and, in combination with cisplatin, response rates of 30% to 60%. Carboplatin causes much less nonhematologic toxicity than cisplatin, and initial therapy with carboplatin yields equivalent survival in advanced non-small cell lung cancer compared with cisplatin combinations and other cisplatin analogs, despite a lower response rate. Carmichael and colleagues have identified a maximum tolerated dose of carboplatin of area under the curve 5.2 mg/mL/min administered monthly in combination with gemcitabine 1,000 mg/m2 on days 1, 8, and 15. This combination produced a response rate of 31% and a median survival of 45 weeks in 13 evaluable patients. A subsequent phase I evaluation reversing the carboplatin and gemcitabine sequence (gemcitabine --> carboplatin day 1) demonstrated no difference in toxicities, pharmacodynamics, or maximum tolerated dose. At Fox Chase Cancer Center and elsewhere, similar phase I trials will determine the maximum tolerated doses of each agent in combination using a compressed schedule with carboplatin administered every 3 weeks and gemcitabine given on days 1 and 8 only.
Langer
C J
CJ
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Calvert
P
P
Ozols
R F
RF
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine