Phase I/II study of gemcitabine and vinorelbine plus cisplatin in non-small cell lung cancer.
OBJECTIVE
We determine the maximum tolerated dose (MTD) and efficacy of gemcitabine plus vinorelbine combined with cisplatin in patients with non-small cell lung cancer (NSCLC).


METHODS
Chemo naive patients with stage IIIA to IV non-small cell lung cancer received outpatient administration of gemcitabine 1,000 mg/m2 and vinorelbine 25 mg/m2 intravenously on days 1 and 8 every 21 days. Doses of gemcitabine and vinorelbine were escalated by 250 mg/m2 and 5 mg/m2, respectively, at each dose level. Cisplatin was administered at a fixed dose of 50 mg/m2 on days 2 and 9. After the MTD was reached, the study was continued as a phase II trial.


RESULTS
From January 1998 to March 1999, sixty-five patients were enrolled. The first 38 patients participated in the phase I evaluation. After 130 cycles, the dose-limiting toxicities were neutropenia, stomatitis, asthenia, and hepatotoxicity occurring at the third and fourth dose levels (doses of gemcitabine/vinorelbine of 1,500/25 and 1,000/30 mg/m2). For the subsequent phase II evaluation, 27 additional patients, out of a total of 53, receiving the MTD of gemcitabine and vinorelbine (1000-1250/25 mg/m2) followed (24 hours later) by cisplatin 50 mg/m2. Thirty one (58%) of 53 assessable patients responded. Objective response for patients with stages III and IV disease, respectively, were 65% and 47%. The median time to progression and the overall survival time were 9 months (95% CI: 5-12) and 11 months (95% CI: 9-13), respectively. World Health Organization toxicity > or = grade 3 neutropenia was registered in 28 (54%) of 52 assessable patients (2% with febrile neutropenia), and > or = grade 3 thrombocytopenia in 15 (29%) patients (4% with bleeding). Nausea/vomiting (> or = grade 2) and asthenia (moderate to severe) occurred in 24 (46%) and 14 (27%) patients, respectively.


CONCLUSIONS
Gemcitabine 1,000-1,250 mg/m2 plus vinorelbine 25 mg/m2 on days 1 and 8, followed by cisplatin 50 mg/m2 24 hours later, is safe for outpatient administration and active in patients with NSCLC.
Esteban
Emilio
E
Servicio de Oncología Medica, Hospital Central de Asturias, Oviedo, Spain. eestebang@seom.org
Fra
Joaquín
J
Sala
Marian
M
Carrasco
Juan
J
Corral
Norberto
N
Vieitez
José María
JM
Estrada
Enrique
E
Palacio
Isabel
I
Buesa
José María
JM
Lacave
Angel J
AJ
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D017567:Karnofsky Performance Status; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013534:Survival; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine; D000093542:Gemcitabine
D000900:Anti-Bacterial Agents; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine