Phase I/II study of gemcitabine plus vinorelbine in non-small cell lung cancer.
BACKGROUND
Because gemcitabine and vinorelbine have demonstrated single-agent activity in non-small cell lung cancer (NSCLC), we conducted this phase I/II study to determine the maximum tolerated dose (MTD) and activity of these drugs combined.


METHODS
Patients with inoperable or advanced NSCLC and no prior chemotherapy were treated with gemcitabine plus vinorelbine on days 1 and 8 every 21 days. The initial doses of gemcitabine 1,000 mg/m2 and vinorelbine 25 mg/m2 were escalated by 250 mg/m2 and 5 mg/m2, respectively, in separate patient cohorts until the MTD was established.


RESULTS
In phase I, 32 patients received a total of 115 cycles. Dose-limiting toxicities were neutropenia and hepatotoxicity, occurring at the dose level of 1,500 mg/m2 and 30 mg/m2. Thus, the MTD used for phase II was 1,250 mg/m2 and 30 mg/m2. Of 41 patients in phase II, 16 (39%) achieved objective responses (95% confidence interval [CI] 24% to 54%), with a median time to progression of 4.2 months. Overall survival was 9 months (95% CI 5.7 to 12.7 months) and the 1-year survival rate was 31%. World Health Organization (WHO) > or = grade 3 neutropenia and reversible thrombocytosis occurred in 15% and 65% of patients, respectively. Non-hematologic toxicity was mild at all dose levels. Grades 3 and 4 hepatotoxicity were reported in one patient each.


CONCLUSIONS
The combination of 1,250 mg/m2 gemcitabine and 30 mg/m2 vinorelbine on days 1 and 8 every 21 days is well tolerated and active in patients with NSCLC. These results should be confirmed in comparative studies.
Esteban
Emilio
E
Medical Oncology Department, Hospital Central de Asturias, Oviedo, Spain. emilioes@ene.es
Fra
Joaquin
J
Corral
Norberto
N
Valle
Miguel
M
Carrasco
Juan
J
Sala
Marian
M
Puerta
Javier
J
Estrada
Enrique
E
Palacio
Isabel
I
Vieitez
Jose Maria
JM
Buesa
Jose Maria
JM
Lacave
Angel Jimenez
AJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D000077235:Vinorelbine; D000093542:Gemcitabine
D003841:Deoxycytidine; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine