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).
The findings stem from a 17-center, double-blind, randomized trial
conducted by the European SCLC Study Group.
The 300 previously untreated patients enrolled in this trial were
first 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 day
3; and vincristine, 0.5 mg on day 14) either at the usual 4-week
intervals or on an accelerated every-3-week schedule.
In a second randomization, patients were assigned to treatment
with either GM-CSF, 200 mg/m²/day, or placebo for 14 days
between courses. Approximately two fifths of patients in both
treatment 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 received
the more aggressive VICE regimen.
Somewhat surprisingly, among patients treated at three-week intervals,
the incidence of febrile neutropenia was no higher than that of
the group treated every 4 weeks, and the rate of treatment-related
death was actually lower. The use of GM-CSF appeared to have no
effect on the dose intensity delivered in both groups, Dr. Steward
The complete response rate was 50% in both treatment groups, with
a 90% overall response rate in the dose-intensified arm and a
77% response rate in the standard arm, a difference that did not
reach significance. However, the survival advantage with dose
intensification 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 survival
rate was 33% in the intensive arm and 20% in the fixed arm,"
Dr. Steward said. These differences held whether patients received
GM-CSF or placebo.
"We feel that the intensification of this chemotherapy regimen
provides a useful survival benefit, with no increased risk of
sepsis or toxic death," Dr. Steward said. "For patients,
there is the benefit that chemotherapy is completed earlier and
they have a longer survival without the need for continued chemotherapy,
although there is a slight penalty to pay in that there is an
increased transfusion requirement in the intensified arm."