NEW ORLEANS—First-line treatment with carboplatin(Drug information on carboplatin) (Paraplatin) and paclitaxel(Drug information on paclitaxel) (Taxol) given every 4 weeks is well tolerated in patients with extensive small-cell lung cancer (SCLC), according to a multicenter phase II trial conducted in Italy and reported at the 36th Annual Meeting of the American Society of Clinical Oncology (ASCO).
While carboplatin plus paclitaxel has demonstrated efficacy as second-line therapy, there have been no studies of this combination as first-line therapy in SCLC, Francesco Perrone, MD, of the National Cancer Institute, Naples, Italy, told ONI at his poster presentation. The principal author of the poster was L. Manzione, MD.
The study enrolled 48 patients with extensive SCLC; 8% had asymptomatic brain metastases and 19% had poor performance status. The patients received first-line therapy with carboplatin (AUC 6) plus paclitaxel (175 mg/m² over 3 hours) on day 1, every 4 weeks, for a median of six cycles.
About half the patients received all six planned cycles, and 23 patients discontinued treatment because of disease progression or toxicity.
Objective response, the primary endpoint, was obtained in 26 patients (54%); 3 were complete responses (6.2%), and 23 were partial responses (47.9%). Stable disease was noted in 8 patients (16.7%).
At the time of analysis, 43 patients had progressed (90%), with a median time to progression of 5.7 months. Thirty-three patients (69%) died, and median survival was 9.6 months, Dr. Perrone said.
Overall toxicity was mild. Only two patients stopped therapy because of toxicity. One had grade 4 hepatic toxicity after cycle 4; this patient had developed grade 1 toxicity during cycles 1 and 3, but had recovered before subsequent doses. Another patient developed a fatal allergic reaction after cycle 1.
There was no difference in the incidence or degree of toxicity between patients who did and did not receive prophylactic G-CSF (Neupogen) except for grade 2-3 thrombocytopenia, which occurred only in patients on G-CSF.
The investigators concluded that carboplatin plus paclitaxel is very well tolerated, but was not sufficiently active in this study to warrant a phase III comparison with standard chemotherapy regimens for extensive SCLC.
“The dose intensity of both drugs and the Taxol dose per cycle were in the lower range of doses administered as a 3-hour infusion, lower as compared to schedules commonly used in other solid tumors,” Dr. Perrone noted. “We concluded that the two-drug combination should undergo further trials before recommending a phase III study. These results were in the range of what you can obtain with cisplatin(Drug information on cisplatin) [Platinol]/etoposide, the standard therapy, and the cost is higher.”
