The delivery of chemotherapy simultaneously with radiotherapy
may be the optimal way to improve survival in patients with non-small-cell
lung cancer (NSCLC). The median survival time of the 79 patients
in a nonrandomized pilot trial (RTOG 91-06) was 19 months.
"These are by far the best results yet reported with nonoperative
therapy for locally advanced non-small- cell lung cancer in a
national trial," Walter J. Curran, Jr., md, said at the American
Cancer Society Science Writers Seminar.
A survival benefit for simultaneous versus sequential chemotherapy/radiotherapy
has been demonstrated for localized small-cell lung cancer, but,
until now, such data have not existed for NSCLC, said Dr. Curran,
of Thomas Jefferson University, Philadelphia, who was representing
the Radiation Therapy Oncology Group (RTOG).
Sequential vs Simultaneous Therapy
The survival benefit of sequential therapy over radiotherapy alone
in NSCLC has been shown in four randomized trials that focused
on stage III patients with unresected, locally advanced NSCLC
and good performance status.
The most recent of these, RTOG 88-08, noted an improvement in
median survival from 11 to 14 months with the addition of two
cycles of cisplatin (Platinol) and vinblastine given prior to
thoracic radiotherapy. Almost 500 patients were enrolled in this
The approach is similar to that of the CALGB 84-33 trial, for
which long-term information is available on 155 patients. Five-year
survival rates for the combination therapy group are 19% vs 7%
for the radiation-only group, Dr. Curran said.
The advantage of simultaneous administration is to employ all
active therapies immediately, with the potential for "supra-additive
synergism in the regimen's antitumor activity," he explained.
The regimen of the current trial included two high-dose cycles
of cisplatin and oral etoposide (VePesid) concurrently with twice-daily
radiotherapy. Chemotherapy and radiotherapy were begun on the
same day. The 79 patients are from 30 RTOG centers.
One Major Complication
The benefit in survival, however, was gained at the cost of an
increase in one major complication-severe esophagitis-which, in
fact, was to be expected with a more potent therapeutic approach.
Severe esophagitis (grade 3) occurred in 36% of patients, most
of whom required intravenous tube feeding or hyperalimentation.
More than half the patients in the study also demonstrated grade
3 or worse reversible hematologic toxicity, he said.
In contrast, severe esophagitis occurs in less than 5% of patients
who receive radiotherapy alone or sequential chemotherapy/radiotherapy.
"This outcome will only be worth accepting if we can significantly
affect survival," Dr. Curran commented.
The results of the pilot trial were sufficiently encouraging to
spawn a currently active randomized trial (RTOG 94-10 } comparing
sequential to simultaneusly administered chemotherapy/radiotherapy
in 600 patients . Drug protocols will include cisplatin, vinblastine,
and oral etoposide.}