PHILADELPHIA-Phase III preliminary trial results support the continued use and development of concurrent chemoradiation strategies for patients with unresected stage III non–small-cell lung cancer (NSCLC).
PHILADELPHIAPhase III preliminary trial results support the continued use and development of concurrent chemoradiation strategies for patients with unresected stage III nonsmall-cell lung cancer (NSCLC).
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.
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.