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.
The delivery of chemotherapy simultaneously with radiotherapymay be the optimal way to improve survival in patients with non-small-celllung cancer (NSCLC). The median survival time of the 79 patientsin a nonrandomized pilot trial (RTOG 91-06) was 19 months.
"These are by far the best results yet reported with nonoperativetherapy for locally advanced non-small- cell lung cancer in anational trial," Walter J. Curran, Jr., md, said at the AmericanCancer Society Science Writers Seminar.
A survival benefit for simultaneous versus sequential chemotherapy/radiotherapyhas 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 representingthe Radiation Therapy Oncology Group (RTOG).
Sequential vs Simultaneous Therapy
The survival benefit of sequential therapy over radiotherapy alonein NSCLC has been shown in four randomized trials that focusedon stage III patients with unresected, locally advanced NSCLCand good performance status.
The most recent of these, RTOG 88-08, noted an improvement inmedian survival from 11 to 14 months with the addition of twocycles of cisplatin (Platinol) and vinblastine given prior tothoracic radiotherapy. Almost 500 patients were enrolled in thistrial.
The approach is similar to that of the CALGB 84-33 trial, forwhich long-term information is available on 155 patients. Five-yearsurvival 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 allactive therapies immediately, with the potential for "supra-additivesynergism in the regimen's antitumor activity," he explained.
The regimen of the current trial included two high-dose cyclesof cisplatin and oral etoposide (VePesid) concurrently with twice-dailyradiotherapy. Chemotherapy and radiotherapy were begun on thesame day. The 79 patients are from 30 RTOG centers.
One Major Complication
The benefit in survival, however, was gained at the cost of anincrease in one major complication-severe esophagitis-which, infact, was to be expected with a more potent therapeutic approach.Severe esophagitis (grade 3) occurred in 36% of patients, mostof whom required intravenous tube feeding or hyperalimentation.More than half the patients in the study also demonstrated grade3 or worse reversible hematologic toxicity, he said.
In contrast, severe esophagitis occurs in less than 5% of patientswho receive radiotherapy alone or sequential chemotherapy/radiotherapy."This outcome will only be worth accepting if we can significantlyaffect survival," Dr. Curran commented.
The results of the pilot trial were sufficiently encouraging tospawn a currently active randomized trial (RTOG 94-10 } comparingsequential to simultaneusly administered chemotherapy/radiotherapyin 600 patients . Drug protocols will include cisplatin, vinblastine,and oral etoposide.}