Activity and toxicity of gemcitabine and gemcitabine + vinorelbine in advanced non-small-cell lung cancer elderly patients: Phase II data from the Multicenter Italian Lung Cancer in the Elderly Study (MILES) randomized trial.
BACKGROUND
Following the demonstration that vinorelbine improves survival and quality of life compared with best supportive care in elderly patients with advanced non-small-cell lung cancer (NSCLC), we started the three-arm prospective Multicenter Italian Lung Cancer in the Elderly Study (MILES) trial of vinorelbine, gemcitabine and gemcitabine + vinorelbine.


METHODS
Within the randomized phase 3 trial, pilot single-stage phase 2 studies were planned for gemcitabine and for gemcitabine + vinorelbine. Eligible patients are aged 70 or more, with stage IV or IIIb (with metastatic supraclavear nodes or malignant pleural effusion) NSCLC. Single-agent gemcitabine is given at 1200 mg/m(2) on days 1 and 8; in the combination, gemcitabine is given at 1000 mg/m(2) and vinorelbine at 25 mg/m(2), both on days 1 and 8, every 3 weeks.


RESULTS
As planned 49 patients were enrolled in each group. Median age was 74 in both groups. Two-thirds of patients had stage IV disease. The response rate was 18.4% (95% exact CI 8.8-32.0) with both treatments. With single-agent gemcitabine main toxicities were grade 4 thrombocytopenia and grade 2 hepatic toxicity, in one patient each, and grade 2 pulmonary toxicity in two patients. With gemcitabine + vinorelbine combination there were grade 4 neutropenia and thrombocytopenia (one patient each), grade 3 anemia requiring red blood cell transfusion (two patients), and grade 4 fever in two patients. Four patients, with severe cardiac comorbidities, suffered grade 3 heart toxicity with atrial flutter or fibrillation, followed by congestive heart failure responsive to treatment.


CONCLUSIONS
Both single-agent gemcitabine and the gemcitabine + vinorelbine combination are sufficiently active and tolerable to allow continuation of the MILES study.
Gridelli
C
C
Divisione di Oncologioca Medica B, Istituto Nazionale per lo Studio e la Cura dei Tumori, via M. Semmola, 80131 Naples, Italy. cgridelli@sirio-oncology.it
Cigolari
S
S
Gallo
C
C
Manzione
L
L
Ianniello
G P
GP
Frontini
L
L
Ferraù
F
F
Robbiati
S F
SF
Adamo
V
V
Gasparini
G
G
Novello
S
S
Perrone
F
F
D000367:Age Factors; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000139:chemically induced; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077235:Vinorelbine; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine