Phase II Study of Taxol in Patients With Untreated Advanced Non-Small-Cell Lung Cancer

Background: Taxol, a complex plant product (a diterpene) extracted from the bark of Taxus brevifolia, has demonstrated substantial anticancer activity in ovarian and breast cancers, malignant melanoma, and acute myelogenous leukemia. Due to allergic reactions in phase I and early phase II studies, use of a 24-hour infusion of taxol with prophylactic dexamethasone, diphenhydramine, and cimetidine has been recommended. Purpose: In this phase II study, we attempted to determine the efficacy and toxicity of taxol in patients with advanced (stage IIIB or IV) non-small-cell lung cancer who had never received chemotherapy. Methods: Patients were not excluded because of prior surgery or because of radiotherapy administered more than 4 weeks before study entry. Taxol was administered in the hospital at a dose of 200 mg/m2 as an intravenous infusion over 24 hours and repeated every 3 weeks, provided that patients had recovered from any toxic effects. Dexamethasone, cimetidine, and diphenhydramine were given before chemotherapy to prevent hypersensitivity reactions. Therapy was continued for at least two courses unless there was repid disease progression and for at least three courses if no change was observed and no grade 3 or 4 toxic effects occurred. Treatment was continued for six more courses after maximum response or for two more courses after complete remission but was discontinued if disease progressed. Results: Of the 27 patients entered in the study, 25 were assessable for toxic effects and response. One patient had an allergic reaction that was not life threatening. The overall response rate was 24% (one complete response and five partial responses). An additional seven patients (28%) had minor responses. Granulocytopenia was the dose-limiting toxic effect, and neutropenic fever occurred in eight of 118 courses. One additional patient developed neutropenic sepsis with hypotension but recovered with intensive treatment. Conclusions: Taxol appears to have activity against non-small-cell carcinoma of the lung. Implications: A phase II study combining taxol, etoposide, and cisplatin and using hematopoietic stimulating factors is now proposed. The optimal dose for combination chemotherapy has yet to be determined. An important consideration is potential cardiac effects of taxol with other drugs. [J Natl Cancer Inst 85:384–388, 1993]