New Agents in Combination Regimens

The purpose of this trial was to evaluate the efficacy and safety of weekly gemcitabine (Gemzar) plus monthly docetaxel (Taxotere) (J Clin Oncol 16:3866-3873, 1998) as second-line treatment for non–small-cell lung cancer.

Eligibility criteria included measurable non–small-cell lung cancer failing one prior chemotherapy regimen, performance status 0–2, and no prior gemcitabine or taxane. Patients received 800 mg/m² of gemcitabine infused over 30 minutes on days 1, 8, and 15, and 100 mg/m² of docetaxel on day 1, every 28 days. Responses were assessed after the second cycle and confirmed after the fourth cycle.

A total of 40 patients entered the trial between October 1997 and October 1999. Patient characteristics were as follows: male/female ratio, 29/11; median age, 62 years; performance status of 2, 12 patients; stage IV disease, 32 patients. Thirty-six patients had received prior platinum-based chemotherapy, combined with either vinorelbine (Navelbine) (26 patients) or etoposide (10 patients). Four patients had received prior single agents without platinum. Thirteen patients had progressed while receiving first-line chemotherapy (refractory), 17 had stable disease as best response or progressed within 3 months of completing initial therapy (resistant), and 5 had sensitive disease. 126 cycles were administered (median: 3 cycles; range: 1–8 cycles). The relative mean delivered dose intensity was gemcitabine 73%, docetaxel 95%; the weekly gemcitabine schedule was maintained in 62% of cycles.

Hematologic toxicities included grade 4 neutropenia (21 patients), febrile neutropenia (4), grade 3/4 thrombocytopenia (8), packed red blood cell transfusions (9), and platelet transfusions (4). Grade 3 nonhematologic toxicities included asthenia (13 patients), edema (4), emesis (3), mucositis (1), flu-like symptoms (1), diarrhea (1), neuropathy (1), and elevated transaminases (1).

Out of 38 patients assessable for response (2 too early), there were 12 confirmed responses (1 complete response, 11 partial responses), for a response rate of 32% (95% CI: 17%–49%). Responses were seen in 4 of 13 refractory patients, 6 of 17 resistant patients, and 2 of 5 sensitive patients. Responding metastatic sites included lung, nodal, skeletal, brain, subcutaneous, and hepatic. The median time to progression for responding patients is 8 months; two responders remain progression-free at 14+ and 18+ months.

CONCLUSION: This doublet is active and safe, with durable responses observed at all disease sites and in patients with platinum-refractory non–small-cell lung cancer.

* Supported by Eli Lilly and Rhône-Poulenc Rorer

Click here for Dr. Vincent A. Miller’s commentary on this abstract.