Paclitaxel and gemcitabine combination in a biweekly schedule in patients with advanced non small-cell lung cancer: a phase I study.
OBJECTIVE
This phase I study was designed to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of the paclitaxel-gemcitabine combination in a biweekly schedule in chemotherapy-naive patients with advanced non small-cell lung cancer (NSCLC).


METHODS
Treatment was administered on an outpatient basis every 2 weeks: paclitaxel over a 1-h IV infusion and gemcitabine as a 30-min IV infusion immediately following paclitaxel.


RESULTS
Twenty-nine patients were treated at six different dose levels, ranging from paclitaxel 135-175 mg/m2 and gemcitabine 1,500-3,000 mg/m2. A total of 198 cycles were administered (median 7, range 1-13). DLTs in the first two cycles were grade 4 neutropenia and myocardial ischemia at the dose level paclitaxel/gemcitabine 150/2,000 mg/m2, febrile neutropenia and grade 4 neutropenia at the dose level paclitaxel/gemcitabine 175/2,500 mg/m2, fatal pneumonitis, sudden death and grade 3 neutropenia at the dose level paclitaxel/gemcitabine 175/3,000 mg/m2. The MTD was paclitaxel 175 mg/m2 and gemcitabine 2,500 mg/m2. The average dose intensity at this dose level was 98%. The overall intent-to-treat response rate was 35.7% (95% confidence interval [CI] 17.97%-53.47%). Overall median survival was 36 weeks (95% CI, 24-48).


CONCLUSIONS
Paclitaxel and gemcitabine can be safely administered at a high dose intensity on an every-other-week schedule. The recommended phase II dose is paclitaxel 175 mg/m2 and gemcitabine 2,500 mg/m2.
Athanasiadis
Athanasios
A
Oncology Department, General Hospital of Larissa, Tsakalof 1, 41 221, Larissa, Greece. athanath@otenet.gr
Roussos
George
G
Papakostoulis
Thomas
T
Athanasiadou
Daniela-Carmen
DC
Stathopoulos
George P
GP
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006402:Hematologic Diseases / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010045:Outpatients; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D015996:Survival Rate; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine