Phase I combination trial of gemcitabine, paclitaxel, and carboplatin in patients with advanced malignancy.
OBJECTIVE
We performed a phase I trial of carboplatin and paclitaxel in combination with gemcitabine in order to determine the tolerability of this triplet.


METHODS
Enrolled in the study were 26 patients with advanced cancer, most with non-small cell lung cancer. The patients received escalating doses of carboplatin and paclitaxel on day 1 and gemcitabine (30-min infusion) on days 1, 8, and 15 of a 28-day treatment cycle. The doses of each drug ranged from an area under the concentration-time curve (AUC) of 5 to 6 for carboplatin, 135 to 175 mg/m(2) for paclitaxel, and 300 to 1000 mg/m(2) for gemcitabine.


RESULTS
Hematologic toxicity was the most commonly observed toxicity and was dose-limiting. During the first cycle at the recommended phase II dose, there were two instances of grade 4 neutropenia and one instance of grade 4 thrombocytopenia among six patients, none of which was dose-limiting. Cumulative hematologic toxicity emerged in subsequent cycles. Non-hematologic toxicities were mild. Five patients, all with previously untreated non-small-cell lung cancer (NSCLC), had a partial response. Nine patients with NSCLC or upper gastrointestinal malignancies experienced stable disease.


CONCLUSIONS
Based on significant neutropenia and thrombocytopenia, the regimen recommended for further study consists of carboplatin AUC 5, paclitaxel 175 mg/m(2), and gemcitabine 1000 mg/m(2) on a 28-day cycle. The antitumor activity noted suggests that further investigation of this well-tolerated combination in specific tumor types, especially NSCLC, is warranted.
Flaherty
Keith T
KT
Abramson Cancer Center, University of Pennsylvania, Medical Arts Buildingm Suite 103, 39th & Market Streets, Philadelphia, PA 19104, USA.
Stevenson
James P
JP
Hahn
Stephen M
SM
Redlinger
Maryann
M
O'Dwyer
Peter J
PJ
D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine