NEW ORLEANSFirst-line treatment with carboplatin (Paraplatin)
and 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
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 [Platinol]/etoposide, the standard therapy, and the
cost is higher.