PHILADELPHIAPhase III preliminary trial results support the
continued use and development of concurrent chemoradiation strategies
for patients with unresected stage III nonsmall-cell lung
The initial results of RTOG 9410, which compared sequential and
concurrent chemoradiation for patients with locally advanced NSCLC,
were presented by Walter J. Curran, Jr., MD, a coauthor of the study,
at the 36th Annual ASCO Meeting.
There is randomized evidence of a survival benefit for
chemoradiation over radiation alone among good-performance-status,
stage III NSCLC patients who have unresected disease, said Dr.
Curran, chairman of radiation oncology and clinical director of the
Kimmel Cancer Center of Thomas Jefferson University, Philadelphia.
Known advantages of sequential chemoradiation include availability of
long-term data, lower toxicity, greater ability to give full-dose
therapy, and a lower incidence of distant failure.
Concurrent therapy advantages include potential synergism and
interaction among both the chemotherapeutic agents and each one of
the agents with radiotherapy, available randomized data, a lower
incidence of chest failure, and a number of encouraging phase II
studies, Dr. Curran said.
Two Primary Objectives
There really were two primary objectives of RTOG 9410, he
said. One was to determine if the concurrent delivery of two
cycles of vinblastine and cisplatin and standard radiation would
improve survival of these patients over the same therapies delivered
sequentially, he said.
The second objective was to determine if concurrent delivery of
cisplatin and oral etoposide and twice daily radiation would improve
survival over the same group of patients receiving sequential
vinblastine, cisplatin, and standard thoracic radiation.
Arm 1, the standard sequential chemoradiation group, included
vinblastine given in a weekly schedule at 5 mg/m² for 5 weeks,
cisplatin given twice prior to radiotherapy on days 1 and 29 at a
dose of 100 mg/m², and, beginning on day 50, radiotherapy given
in 1.8 to 2.0 Gy fractions to a total dose of 63 Gy.
Arm 2 included the same chemotherapeutic agents at the same dose and
schedule as arm 1. Radiotherapy, however, began on day 1 rather than
on day 50.
Arm 3 included oral etoposide 50 mg twice daily over 10 days repeated
three times plus cisplatin 50 mg/m² on days 1, 8, 29, and 36.
Radiotherapy was initiated on day 1 and delivered in 1.2 Gy
twice-daily fractions to a total dose of 69.6 Gy.
Eligibility criteria in this study required patients to have a newly
diagnosed, untreated NSCLC. It had to be either unresected stage IIIA
or stage IIIB disease or medically inoperable stage II disease.
Patients had to have a Karnofsky performance status (KPS) of 70 or
above and no greater than 5% weight loss over the prior 3 months with
normal renal, hematologic, and liver function. No prior chemotherapy
or thoracic radiation could have been delivered.
Results showed that of the 597 evaluable patients, the rates of grade
3-4 nonhematologic toxicity were higher with concurrent than
sequential therapy, but late toxicity rates were similar.
Response rate as judged by clinical criteria was significantly
better in arm 2 compared to arm 1, with the overall response rate
being 68% compared to 59%, and a complete response rate of 41%
compared to 26%, Dr. Curran said. No such difference was
noted in arm 3.
Median survival for arm 1 was 14.6 months; for arm 2, 17.0 months;
and for arm 3, 15.6 months.
My conclusions from this initial report are that the phase II
results of survival and toxicity of arm 2 have been confirmed in this
randomized trial, Dr. Curran said. The phase II results
of arm 3 have not been confirmed with respect to survival but have
been with respect to toxicity.