Docetaxel and carboplatin as first-line therapy in advanced non-small cell lung carcinoma: a phase II study.

Background: Taxanes have been widely used against advanced non-small cell lung cancer (NSCLC), alone and in combination with platinum agents. In order to develop a tolerable palliative regimen, we combined carboplatin with low dose docetaxel. Patients and Methods: Chemotherapy-naive patients, with Stage IIIB or IV NSCLC and an ECOG performance status ≤2, were enrolled. Treatment consisted of docetaxel 60 mg/m 2 and carboplatin AUC 6 every 21 days. Therapy continued for 1 year or 6 months beyond best response, whichever was greater. Results: Twenty-five patients were enrolled. Most patients (80%) had Stage IV disease. The partial response rate was 16%. Response duration ranged from 6 to 115 weeks. Median survival was 55 weeks. Toxicity was generally limited to grade 3 or 4 neutropenia. There was 1 septic death. Conclusion: Survival compared favorably to other similar trials employing higher doses of docetaxel. Additionally, a hematologic toxicity advantage was seen compared to regimens containing higher doses of docetaxel. Most patients with non-small cell lung cancer (NSCLC) present with either locally advanced or metastatic disease (Stage III inoperable or Stage IV). With chemotherapy, newly diagnosed advanced NSCLC patients have an expected median survival of 6 to 8 months (1,2). Current treatment goals in this patient population are to break this survival barrier and reduce disease and treatment-related adverse effects. Platinum and taxane doublets are the accepted regimen based on safety and efficacy profiles. Although paclitaxel is more commonly used in NSCLC, docetaxel has shown single-agent activity at doses ranging from 60 to 100 mg/m 2 in chemotherapy- naive patients (3-6), as well as in patients failing previous cisplatin-based regimens(7-9). At the time this study was initiated, docetaxel had exhibited promising activity and acceptable toxicity when combined with cisplatin or carboplatin in phase I and phase II trials in NSCLC (10). Additionally, it was approved in 2002 for first-line treatment of locally advanced or metastatic NSCLC in combination with cisplatin. When choosing a platinum agent, carboplatin is more appealing in the clinic setting and to the patient compared to cisplatin. As an analogue of cisplatin, carboplatin shows similar efficacy in the NSCLC population with less emetogenicity, neurotoxicity and ototoxicity, while its lower nephrotoxicity allows administration without additional hydration therapy.