BARCELONA, SpainIn a phase I study, 70% of small-cell lung
cancer patients with extensive disease had objective responses when
given carbo-platin (Paraplatin) and epirubicin (Ellence) in combination.
Conducted by the Spanish Lung Cancer Group, the study was designed to
discover whether the combination was active against the disease in a
clinical setting and to determine the maximum tolerated dose,
reported Bartomeu Massuti Sureda, MD.
Dr. Massuti, chief of the Medical Oncology Department, Alicante
University Hospital, Barcelona, noted that the study followed a
randomized phase III trial showing a combination of cisplatin and
epirubicin to be at least as effective as cisplatin and etoposide
without increasing toxicity. Also conducted by the Spanish Lung
Cancer Group, that trial involved more than 400 patients.
Rationale for Study
A rationale for the most recent study, Dr. Massuti told ONI,
was that combining the anthracycline epirubicin with carboplatin
might be even better tolerated. An aim, he added, was to design
more convenient schedules for the patient with extensive disease,
because in these patients cure is not possible, and carboplatin
offers a more convenient toxicity profile than cisplatin.
The maximum tolerated dose turned out to be carbo-platin at AUC 6 and
epirubicin 100 mg/m² administered intravenously on day 1 of
21-day cycles. All six regimens tested followed the same cycle
pattern and combined carboplatin at either AUC 5 or AUC 6 with three
different dosages of epirubicin75, 90, and 100 mg/m².
A total of 30 patients were enrolled in the study, 28 males and 2
females, with a mean age of 63 years. To be eligible, patients had to
have extensive disease with at least one metastatic lesion, no prior
chemotherapy, adequate renal, hepatic, and bone marrow function and a
life expectancy of 3 months or more. The most frequent site of
metastatic disease was the liver; 16 patients had liver lesions. The
median performance status was 80 on the Karnofsky Index.
Nine of the 30 patients (30%) had complete responses, and 12 (40%)
had partial responses, Dr. Massuti reported. Only 2 out of 30
patients progressed during the first cycle. The number of
cycles of treatment per patient ranged from 1 to 6, with the total
Among the six patients receiving the lowest dosages of both drugs,
carboplatin AUC 5 and epirubicin 75 mg/m², one developed grade 3
mucositis, which was considered dose limiting. When epirubicin was
increased to 90 mg/m² but carboplatin held at AUC 5, two of six
patients showed dose-limiting toxicities, one septic shock and the
other grade 4 thrombocytopenia. Two of the six patients given
epirubicin 100 mg/m² and carboplatin AUC 5 developed
dose-limiting neutropenia, one grade 3 and the other grade 4.
None of the three patients given carboplatin AUC 6 and epirubicin 75
mg/m² had dose-limiting toxicities. Among the six whose
epirubicin dosage was 90 mg/m², one required a treatment delay
of more than 7 days and another suffered neutropenic fever and grade
4 neutropenia, Dr. Massuti reported. At the highest dose level for
both drugs, he added, two out of three patients showed
Weekly analyses of blood counts during the first two cycles of
treatment revealed no cumulative toxicity, Dr. Massuti said, but
myelotoxicity increased along with dose level. Grade 4
neutropenia, he added, was the median at the two highest dosage levels.
Phase II Study Beginning
A phase II study to look at time to disease progression and survival
rates will begin this fall at the 14 centers in the Spanish Lung
Cancer Group, Dr. Massuti told ONI. The dosage to be tested
will be carboplatin AUC 6 and epirubicin 90 mg/m², or one level
below the maximum tolerated dose in the phase-I study, with both
again given on day 1 of 3-week cycles.