LISBON, Portugal-New phase III trials testing novel combinations of platinums and taxanes in patients with small-cell lung cancer (SCLC) are yielding encouraging results, according to two studies presented at the 11th European Cancer Conference (ECCO).
LISBON, PortugalNew phase III trials testing novel combinations of platinums and taxanes in patients with small-cell lung cancer (SCLC) are yielding encouraging results, according to two studies presented at the 11th European Cancer Conference (ECCO).
The Norwegian Lung Cancer Group (abstract 556) has reported that, for patients with limited disease, treatment with cisplatin (Platinol) and etoposide (VePesid) (EP) results in significantly better survival at 2 and 5 years than does a regimen of cyclophosphamide, epi-rubicin (Ellence), and vincristine (CEV).
In addition, the findings of a multi-center German trial (abstract 557) indicate that, in patients with extensive disease, the combination of paclitaxel (Taxol) plus etoposide plus carboplatin (Paraplatin) (TEP) prolongs 2- and 3-year survival, compared with standard chemotherapy consisting of carboplatin, etoposide, and vincristine (PEV).
The Norwegian national study enrolled 436 SCLC patients under the age of 75, all of whom had an ECOG performance status of 0 to 2 and adequate renal and bone marrow function, noted Dr. Stein Sundstrøm, from the University Hospital of Trondheim.
"We feel we can claim that the study population reflected real life," Dr. Sundstrøm said. He pointed out that the pool of participants represented 40% of all eligible candidates in Norway and that the treatment was carried out at 25 different hospitals, including small county hospitals.
Patients randomized to the EP arm received five courses of etoposide 100 mg/m² IV and cisplatin 75 mg/m² on day 1, followed by oral etoposide 200 mg/m² on days 2 to 4. Those assigned to CEV chemotherapy were given five cycles of cyclophosphamide 1,000 mg/m², vincristine 2 mg/m², and epirubicin 50 mg/m², all on day 1.
The 218 trial participants with limited disease also received thoracic radiotherapy between chemotherapy cycles 3 and 4. Complete responders underwent prophylactic cranial irradiation as well.
For the limited-stage disease group, there was a highly significant difference in overall survival in favor of the EP arm (P = .0001) that was maintained throughout 5 years of follow-up," Dr. Sundstrøm said. In this subgroup, median survival was 14.5 months with EP vs 9.7 months with CEV; 2-year survival was 25% with EP vs 8% with CEV, and 5-year survival was 10% with EP vs 3% with CEV.
In contrast, for patients with extensive disease, neither chemotherapy regimen afforded any advantage in terms of long-term survival.
The EORTC Quality of Life Questionnaire revealed no significant differences in quality of life between the two treatment arms over the course of the study. Nausea and vomiting were worse among patients who received the EP regimen, however.
German Multicenter Study
The rationale for the phase III German Multicenter Study, explained investigator M. Reck, of Grosshansdorf Hospital, was to determine whether the promising preliminary results achieved with paclitaxel-containing regimens in SCLC would translate into improved patient survival.
"Looking at the phase II data, we observed an overall response rate of 82% with a median survival of 18 months in limited-disease patients, and a response rate between 61% and 68% with a median survival of 9.5 to 13 months in extensive-disease patients," Dr. Reck said.
The 606 chemotherapy-naïve small-cell lung cancer patients enrolled in the phase III German trial were randomly assigned to receive six cycles of TEP (etoposide 110 or 90 mg/m² on days 1 to 3 plus paclitaxel 175 mg/m² on day 4 plus carboplatin to AUC 5 on day 4) or PEV (carboplatin to AUC 5 on day 1 plus etoposide 110 or 140 mg/m² on days 1 to 3 plus vincristine 2 mg on days 1 and 8).
The overall response rate was 82% among patients who received TEP, compared with 76% in the PEV arm (difference not significant).
"In the subgroup of extensive-disease patients, there was a trend in favor of the TEP arm in terms of patterns of response," Dr. Reck said.
Median progression-free survival in the TEP arm was 8 months, 1 month longer than the median progression-free survival of 7 months in the PEV arm, a statistically significant difference.
Kaplan-Meier curves for 2- and 3-year survival showed that the TEP regimen was significantly superior to PEV treatment. The long-term survival benefits were especially prominent for patients with extensive disease.
Dr. Reck noted that there were significantly more severe (CTC 3-4) anemias and thrombocytopenias in the PEV arm: CTC 3-4 anemia, 2.8% vs 5.6% TEP vs PEV, and CTC 3-4 thrombocytopenia 3.3% vs 13.1% TEP vs PEV.
The 20 fatal cases of hematologic toxicity in this study, however, were equally distributed between the two treatment arms, Dr. Reck said.
The incidence of nonhematologic toxicity was lower among patients receiving the TEP regimen.
"It is worthwhile to treat extensive-disease SCLC patients with very intensive regimens because their chances of survival increase," Dr. Reck commented. "At the same time, we have to improve our treatment of patients with limited disease."