Phase III Study of the Eastern Cooperative Oncology Group (ECOG 2597): Induction Chemotherapy Followed by Either Standard Thoracic Radiotherapy or Hyperfractionated Accelerated Radiotherapy for Patients With Unresectable Stage IIIA and B Non–Small-Cell Lung Cancer
ABSTRACT To compare once-daily radiation therapy (qdRT) with hyperfractionated accelerated radiation therapy (HART) after two cycles of induction chemotherapy.
Eligible patients were treatment naive, and had stage IIIA and B unresectable non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0/1, and normal organ function. Induction chemotherapy consisted of two cycles of carboplatin area under time-concentration curve 6 mg/mL . min plus paclitaxel 225 mg/m2 on day 1. RT consisted of arm 1 (qdRT), 64 Gy (2 Gy/d), versus arm 2 (HART), 57.6 Gy (1.5 Gy tid for 2.5 weeks). A total of 388 patients were needed to detect a 50% increase in median survival from 14 months of qdRT to 21 months of HART; accrual was not achieved and the study closed prematurely.
Of 141 patients enrolled, 83% were randomly assigned after chemotherapy to qdRT (n = 59) or HART (n = 60). Median survival was 20.3 and 14.9 months for HART and qdRT, respectively (P = .28). Overall response was 25% and 22% for HART and qdRT, respectively (P = .69). Two- and 3-year survival was 44% and 34% for HART, and 24% and 14% for qdRT, respectively. Grade > or = 3 toxicities included esophagitis in 14 v nine patients, and pneumonitis in 0 v 6 patients for HART and qdRT, respectively. Any subsequent trials of the HART regimen must address the issues that led to early closure, including slow accrual, logistics of HART, mucosal toxicity, and the fact that concurrent chemoradiotherapy now seems more effective than sequential treatment.
After two cycles of induction chemotherapy with carboplatin-paclitaxel, HART is feasible with an acceptable toxicity profile. Although statistical significance was not achieved and the study closed early, there was a positive statistical trend suggesting a survival advantage with the HART regimen.
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- "Interestingly we note that the only randomised trial which compared sequential with concurrent chemotherapy using an accelerated radiotherapy scheme, found no difference in survival between the arms . Furthermore, the best results reported in a phase III study of chemoradiation in locally advanced NSCLC have come from the combination of 2 cycles of carboplatin-paclitaxel followed by hyperfractionated accelerated radiation therapy (HART) . We think that this approach warrants further investigation. "
ABSTRACT: We conducted a phase II study combining induction chemotherapy with continuous hyperfractionated accelerated radiotherapy (CHART) in locally advanced non-small-cell lung cancer (NSCLC). A total of 40 patients with stage III NSCLC were enrolled. All patients received 3 cycles of chemotherapy followed by CHART (56 Gy in 36 fractions over 12 days). The primary outcome measure was radiation toxicity. Secondary endpoints were response rate, overall survival, disease-free survival and loco-regional progression-free survival. Acute radiation toxicity was minimal and there were no significant late toxicities. The response rate after completion of chemoradiation was 65%. The median and 2-year overall survival, progression-free survival and loco-regional progression-free survivals were 15.7 months, 28%; 12.1 months, 23%; and 26.4 months, 51%, respectively. Induction chemotherapy can be safely combined with CHART. The survival results are consistent with previous studies of chemotherapy followed by accelerated radiotherapy. This approach should be compared with synchronous chemoradiation to determine if it represents a less toxic alternative.Radiotherapy and Oncology 06/2009; 93(3):396-401. DOI:10.1016/j.radonc.2009.04.002 · 4.86 Impact Factor
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ABSTRACT: Over the last few decades, the integration of chemotherapy and radiation has played a crucial role in the management of locally advanced non-small cell lung cancer (NSCLC). Locally advanced NSCLC is a very heterogeneous disease. Because of this heterogeneity, advanced NSCLC can be managed in various ways depending on the bulk of disease, the comorbidities of the patient, and the expertise and resources of the treating physicians and facilities. This review describes the evolution of current treatment strategies and predicted future changes for the management of locally advanced NSCLC.The Cancer Journal 01/2013; 19(3):222-230. DOI:10.1097/PPO.0b013e318293238d · 3.61 Impact Factor