Chemotherapy with Cisplatin and Paclitaxel in Inoperable Non-small Cell Lung Cancer : An Extended Phase II Study *

Background: A phase II study of a cisplatin/paclitaxel combination given on a weekly schedule in the front-line treatment of non-small cell lung cancer (NSCLC) is reported. Patients and Methods: Treatment consisted of an intravenous infusion of cisplatin, 25 mg/m2, and paclitaxel, 80 mg/m2, every week. Chemotherapy was continued until completion of a 22-week treatment plan, disease progression, persistent toxicity, or patient refusal. Results: Seventy-nine patients entered the study. The median number of infusions per patient was 14 (range 0-22). The median dose-intensity was 75% of that projected. Toxicity was generally acceptable, and never life-threatening. Seven complete responses (pathologically documented in 4 patients) and 27 partial responses were observed for an overall response rate of 43%. The estimated median survival and median time to progression was 55 (95% CI: 38-71) and 37 weeks (95% CI: 31-44), respectively. Conclusion: In our experience, the weekly combination of cisplatin and paclitaxel is well tolerated, active and associated with remarkably long survivals. Today, lung cancer represents a major public health concern worldwide, accounting for about 12% of all new cancers in both sexes (1-3). Non-small cell lung cancers (NSCLC), including the varieties of adenocarcinomas, squamous cell and large cell carcinomas of the bronchus, represent 75-80% of all histotypes of lung cancer. Most of the patients with NSCLC present an incurable stage of disease, and 5-year survival across all stages is about 12% (4). Patients with locally advanced (Stage III) or metastatic disease (Stage IV) (5) receive chemotherapy, since first-line platinum-based combinations improve survival, palliate symptoms and ameliorate quality of life (6-9). Unfortunately, there is no consensus on which drug combination or treatment schedule should be recommended in everyday practice (10). Randomized trials seem to support the use of two-drug combinations, containing at least one new agent, such as vinorelbine, gemcitabine, or the taxanes (11). Paclitaxel was the first identified member of a new class of anticancer drugs known as the taxanes, which also includes docetaxel. Paclitaxel promotes the polymerization of tubulin, producing extraordinarily stable and malfunctioning microtubules. This effect provokes the disruption of the normal microtubule dynamics required for cell division and cell death (12). Paclitaxel is indicated as a first-line treatment in patients with NSCLC in combination with cisplatin (13). One of the most important clinical questions regarding the taxanes is the issue of the optimal schedule. A preliminary analysis of weekly administration schedules suggests that this approach yields equivalent efficacy, maintains dose intensity and is associated with lower toxicity (14). Herein, the final results of an extended phase II study of a weekly cisplatin/paclitaxel (C/P) combination in chemotherapy-naïve patients with inoperable or recurrent NSCLC are reported (15). Patients and Methods Eligibility. All patients seen, between December 2001 and April 2004, at the Pulmonary Unit of the "S. Croce e Carle" Hospital, Cuneo, Piedmont, Italy, were eligible for study if they had a cytologically or pathologically documented NSCLC (16). Mixed tumors were acceptable if only non-small cell components were identified. A 70-year age limit was established. Patients relapsing after complete tumor resection or patients incompletely resected were also eligible. Patients had to have had either a measurable or an assessable disease. An Eastern Cooperative Oncology 4685 *From the Cuneo Lung Cancer Study Group (www.culcasg.org), The "S. Croce e Carle" Hospital, Cuneo I-12100, Italy. Correspondence to: Domenico Ferrigno, MD, Struttura Complessa di Pneumologia, Ospedale A. Carle, Azienda Ospedaliera "S. Croce e Carle", Cuneo, I-12100, Italy. Tel: 0039.0171. 616733, Fax: 0039.0171. 616724, e-mail: ferrigno@culcasg.org