Paclitaxel, gemcitabine, and cisplatin in non-resectable non-small-cell lung cancer

Background: Paclitaxel, gemcitabine, and cisplatin are each active in non-small-cell lung cancer (NSCLC), and with different modes of action. Hence, a phase II study combining these drugs were conducted. Patients and methods: Treatment was paclitaxel 110 mg/m(2) and cisplatin 60 mg/m(2) day 1 and 15, with gemcitabine 800 mg/m(2) day 1, 8, and 15, every four weeks. Patients had previously untreated NSCLC, measurable disease, age 18-70 years, performance status less than or equal to 2, and no brain metastases. Results: Among 49 patients, 6 (group 1) received chemotherapy as described above, while 43 patients (group 2) did not receive gemcitabine day 8. In group 1, all experienced grade 4 neutropenia and four achieved a partial response (67%). In group 2, neutropenia grade 4 occured in 58%, with one episode of febrile neutropenia and no toxic death. No other grade 4 toxicities occured, while grade 3 toxicity occured with respect to thrombocytopenia (9%), nausea/vomiting (12%), neurotoxicity (12%), and nephrotoxicity (7%). There were 3 complete and 20 partial responses (response rate 54%, 95% confidence limits 38%-69%), median response duration 29 weeks (range 10-66+), median time to progression 28 weeks (range 4-66+), median survival 46 weeks (4-89+) and one-year survival rate 42%. Conclusion: This regimen of paclitaxel, gemcitabine, and cisplatin has neutropenia as dose limiting toxicity, but septicemic episodes were rare and toxic death did not occur. Other grade 4 toxicities than neutropenia did not occur. The regimen appears safe and with a noteworthy activity both in terms of response rate, time to progression, and survival.