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NEW AGENTS IN THE TREATMENT OF NON-SMALL CELL LUNG CANCER Robert L. Comis, Jefferson Cancer Center, Philadelphia, Pa
Prior to the exploration of the activity of the platinum analogues, the chemotherapy of non-small cell lung cancer (NSCLC) was fraught with inconsistent levels of activity and minimal, if any, impact of survival for any stage of disease. More than 15 years of work has shown that platinum-based therapy provides important effects in intrathoracic and minimal but detectable survival increases in metastatic disease. The need for new agents has been apparent for decades. Several new classes of agents have been shown recently to be active and are the focus of intense new investigation. TAXOL (paclitaxel) has been shown to be active in two separate trials, with response rates ranging from 21 to 24% and survival at 1 year approximating 40%. Combination chemotherapy studies are ongoing. Preliminary studies employing docetaxel (Taxotere) have yielded similar response rates, but with considerable nonhematologic toxicity. CPT-11, a camptothecin derivative, has been shown to induce 30 to 40% objective responses, with reported median survival of 10 months. Combinations with platinum analogues reveal similar objective response rates and dose-limiting gastrointestinal toxicity. Gemcitabine, an antimetabolite with unusual pharmacodynamics, has been reported to induce a 26% objective response. Two analogues of existing agents have shown activity. Vinorelbine, a vinca analogue, has an approximate 30% response rate in over 100 patients. Recent randomized combination studies with platinums have shown survival advantages, which have led to recent FDA approvals. All of these new agents are now undergoing extensive investigations evaluating optimal combination approaches, the initial focus of which is metastatic disease. Combined-modality trials in intrathoracic disease are beginning. Thus, a new foundation of cytotoxic-based research is being explored, while unique explorations of biologic-based therapies are undergoing initial clinical explorations.