Phase III Comparison of Sequential vs Concurrent Chemoradiation for Patients (Pts) with Unresected Stage III Non-Small Cell Lung Cancer (NSCLC): Initial Report of Radiation Therapy Oncology Group (RTOG) 9410.

Jason Lee, MD
OncoLink Assistant Editor
Last Modified: May 20, 2000

Presenter: Walter Curran
Affiliation: Bodine Ctr for Cancer Treatment


  • Radiation therapy with or without chemotherapy is standard therapy for locally advanced unresectable non-small cell lung cancer (NSCLC)

  • The use of sequential cisplatin-based chemotherapy followed by thoracic radiation therapy has been shown to be superior to radiation therapy alone in good performance status patients

  • There has been considerable investigation into improving outcomes with newer chemotherapy agents and concurrent rather than sequential administration of chemotherapy and radiation therapy

Materials and Methods:

  • A phase III multi-institutional three-arm randomized trial was conducted from 7/94-7/98 through the RTOG to determine the optimal sequencing of chemotherapy and dose-fractionation of radiation therapy

  • 611 patients with unresectable stage II and III NSCLC, good performance status and minimal weight loss were enrolled

  • The following regimens were compared using random assignment stratified by stage and performance status: - SEQ: cisplatin (100 mg/m2) and vinblastine (5 mg/m2 weekly) for 2 cycles followed by radiation therapy (60 Gy) - CON-QD: cisplatin (100 mg/m2) and vinblastine (5 mg/m2 weekly) with concurrent radiation therapy - CON-BID: cisplatin (50 mg/m2) and oral etoposide 50 mg BID for 4 weeks with concurrent hyperfractionated radiation therapy (69.6 Gy in 1.2 Gy BID fractions)

  • Patients were analyzed for overall survival (OS), response rates (RR), and toxicity

  • The overall response rates for the three treatment arms were 59% (SEQ), 68% (CON-QD), and 63% (CON-BID)

  • The median survival time (MST) and 5-yr survival with CON-QD was 17.0 mos and 26%, respectively, which represented a borderline improvement (p=0.08) over sequential chemotherapy (14.6 mos MST and 18% 5-yr OS)

  • There was no improvement in the CON-BID arm compared with the SEQ arm

  • Toxicity was higher in both concurrent chemoradiation treatment arms compared with the SEQ arm, particularly in the rates of grade 3-4 esophagitis (25-44% vs. 4%)

  • Late morbidity and fatal toxicities were similar across the three treatment arms
Authors' Conclusions

  • Concurrent chemotherapy and radiation therapy for locally advanced NSCLC results in improved response rates compared with sequential chemotherapy and radiation therapy

  • Acute toxicity in the form of esophagitis is higher with concurrent therapy compared with sequential therapy
Clinical/Scientific Implications:
    Patients with good performance status and unresectable NSCLC should be considered for concurrent chemotherapy and radiation therapy. Future studies should address the question of the optimal chemotherapy regimen for concurrent chemoradiation and making concurrent treatment more tolerable