Lung Cancer.pdf

214 G.R. Blumenschein, Jr.
the years as further evaluation determined the optimum number of
chemotherapy cycles. A number of randomized trials have been conducted
to evaluate the benefit of either prolonged induction chemotherapy
or maintenance therapy. These trials have produced conflicting results,
with a modest increase in survival seen in some trials. However, a
large European Organization for Research and Treatment of Cancer trial
with 577 evaluable patients demonstrated no benefit. Prolonging the duration
of first-line chemotherapy beyond 6 cycles has not been shown to
improve survival and is not considered beneficial in the treatment of extensive-stage
SCLC. Maintenance therapy (the utilization of an alternative
chemotherapy regimen after achieving maximum benefit from first-line
chemotherapy) has not been proven to prolong remission or survival. In
addition, in the randomized trials, patients who were treated with either
prolonged induction chemotherapy or maintenance chemotherapy had
increased chemotherapy-related morbidity. In chemonaive extensivestage
SCLC, maximum responses to chemotherapy generally occur within
the first 3 cycles of treatment. At this time, treatment beyond 6 cycles of
chemotherapy is not recommended in patients with previously untreated
extensive-stage SCLC.
Alternating Chemotherapy Regimens
Inspired by the Goldie-Coldman hypothesis, investigators have studied
the use of alternating non-cross-resistant chemotherapy regimens in patients
with chemotherapy-naive extensive-stage SCLC. In the 1980s,
Goldie and Coldman theorized that the rapid alternation of non-cross-resistant
chemotherapy regimens could improve the tumor cell kill rate.
Various alternating-chemotherapy regimens have been studied over the
years, with mixed results.
Several phase III trials investigated alternation of the 2 primary regimens
used to treat extensive-stage SCLC, CAV and EP. A Canadian study
done in the late 1980s had a positive outcome, with survival data favoring
CAV alternated with EP over the CAV-alone arm (Evans et al, 1987). This
study included 289 patients with extensive-stage SCLC who received either
CAV every 3 weeks for 6 cycles or CAV alternated with EP every 3
weeks for a total of 6 cycles. The median survival times were 8 months for
CAV alone and 9.6 months for the alternating regimen (P .03). The Southeastern
Cancer Study Group then randomly assigned patients with extensive-stage
SCLC to one of 3 regimens: 6 cycles of CAV, 4 cycles of EP, or alternating
CAV with EP (3 cycles each) (Roth et al, 1992). This was a large
study with 437 evaluable patients. No significant differences were found
between the treatment arms in terms of median survival (range, 8.1–8.6
months), response rate, or complete response rate. A similar result was obtained
in a randomized study in which 288 patients with either extensivestage
SCLC or limited-stage SCLC were also treated with CAV, EP, or alternating
CAV and EP (Fukuoka et al, 1991). Although a survival benefit for