For patients with either limited or extensive small-cell lung cancer (SCLC), dose intensification of VICE chemotherapy affords a significant survival advantage without increasing the danger of sepsis or drug-related death, W.P. Steward, MD, said at the Eighth Annual European Cancer Conference (ECCO-8).
For patients with either limited or extensive small-cell lungcancer (SCLC), dose intensification of VICE chemotherapy affordsa significant survival advantage without increasing the dangerof sepsis or drug-related death, W.P. Steward, MD, said at theEighth Annual European Cancer Conference (ECCO-8).
The findings stem from a 17-center, double-blind, randomized trialconducted by the European SCLC Study Group.
The 300 previously untreated patients enrolled in this trial werefirst randomized to receive six courses of the VICE regimen (ifosfamide,5 mg/m² on day 1; carbo-platin, 300 mg/m² on day 1;etoposide 120 mg/m² on days 1 and 2; oral etoposide on day3; and vincristine, 0.5 mg on day 14) either at the usual 4-weekintervals or on an accelerated every-3-week schedule.
In a second randomization, patients were assigned to treatmentwith either GM-CSF, 200 mg/m²/day, or placebo for 14 daysbetween courses. Approximately two fifths of patients in bothtreatment arms had extensive-stage disease.
Dose intensification did indeed prove feasible, said Dr. Steward,of the National Cancer Institute of Canada, Clinical Trials Unit.A 27% greater dose intensity was achieved in the group that receivedthe more aggressive VICE regimen.
Somewhat surprisingly, among patients treated at three-week intervals,the incidence of febrile neutropenia was no higher than that ofthe group treated every 4 weeks, and the rate of treatment-relateddeath was actually lower. The use of GM-CSF appeared to have noeffect on the dose intensity delivered in both groups, Dr. Stewardsaid.
The complete response rate was 50% in both treatment groups, witha 90% overall response rate in the dose-intensified arm and a77% response rate in the standard arm, a difference that did notreach significance. However, the survival advantage with doseintensification proved to be highly significant.
"The median survival was 15 months in the intensive arm,compared with 12 months in the fixed arm, and the 2-year survivalrate was 33% in the intensive arm and 20% in the fixed arm,"Dr. Steward said. These differences held whether patients receivedGM-CSF or placebo.
"We feel that the intensification of this chemotherapy regimenprovides a useful survival benefit, with no increased risk ofsepsis or toxic death," Dr. Steward said. "For patients,there is the benefit that chemotherapy is completed earlier andthey have a longer survival without the need for continued chemotherapy,although there is a slight penalty to pay in that there is anincreased transfusion requirement in the intensified arm."