A phase I dose escalation study of weekly docetaxel and carboplatin in elderly patients with nonsmall cell lung cancer.

OBJECTIVE

We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), the recommended dose (RD), and the safety profile of a weekly docetaxel and carboplatin combination regimen in the treatment of elderly patients with advanced nonsmall cell lung cancer (NSCLC).

PATIENTS AND METHODS

Chemotherapy-naive patients with stage IIIB and IV NSCLC, >70 years of age, performance status (ECOG) 0-2, with adequate bone marrow, renal, liver and cardiac function, were treated with docetaxel and carboplatin. Docetaxel was given at escalated doses starting from 20 mg/m2/wk on days 1, 8, and 15, with an increment of 5 mg/m2 followed by carboplatin also administered at escalated doses starting from AUC 4 to 6 (mg/ml/min); the regimen was administered every 4 weeks. The dose limiting toxicity (DLT) of the regimen was assessed during the first chemotherapy cycle.

RESULTS

There were 25 patients enrolled in this study and assessed for safety. Neutropenia was the main DLT of the regimen; grade 3/4 neutropenia occurred in 5 patients (20%). Hematologic toxicities were mild, and included grade 3 thrombocytopenia in 1 patient (4%) and grade 3 anemia in 1 patient (4%). Nonhematologic toxicities were generally mild, and included grade 3 constipation in 1 patient (4%) and grade 3 renal disorder in 1 patient (4%). Objective responses were seen in 9 patients (response rate 36%).

CONCLUSIONS

The MTD was carboplatin AUC 5 on day 1 and docetaxel 30 mg/m2 on days 1, 8, and 15; therefore, the RD for the phase II study is carboplatin AUC 5 and docetaxel 30 mg/m2. The combination of docetaxel and carboplatin is a feasible and well-tolerated regimen for the treatment of elderly patients with advanced NSCLC. This regimen merits further investigation in phase II trials.