Randomized Phase III Study of Thoracic Radiation in Combination With Paclitaxel and Carboplatin With or Without Thalidomide in Patients With Stage III Non–Small-Cell Lung Cancer: The ECOG 3598 Study

Abstract

A B S T R A C T PurposeThe primary objective of this study was to compare the survival of patients with unresectable stage III non-small-cell lung cancer (NSCLC) treated with combined chemoradiotherapy with or without thalidomide. Patients and MethodsPatients were randomly assigned to the control arm (PC) involving two cycles of induction paclitaxel 225 mg/m 2 and carboplatin area under the curve (AUC) 6 followed by 60 Gy thoracic radiation administered concurrently with weekly paclitaxel 45 mg/m 2 and carboplatin AUC 2, or to the experimental arm (TPC), receiving the same treatment in combination with thalidomide at a starting dose of 200 mg daily. The protocol allowed an increase in thalidomide dose up to 1,000 mg daily based on patient tolerability. ResultsA total of 546 patients were eligible, including 275 in the PC arm and 271 in the TPC arm. Median overall survival, progression-free survival, and overall response rate were 15.3 months, 7.4 months, and 35.0%, respectively, for patients in the PC arm, in comparison with 16.0 months (P ϭ .99), 7.8 months (P ϭ .96), and 38.2% (P ϭ .47), respectively, for patients in the TPC arm. Overall, there was higher incidence of grade 3 toxicities in patients treated with thalidomide. Several grade 3 or higher events were observed more often in the TPC arm, including thromboembolism, fatigue, depressed consciousness, dizziness, sensory neuropathy, tremor, constipation, dyspnea, hypoxia, hypokalemia, rash, and edema. Low-dose aspirin did not reduce the thromboembolic rate. ConclusionThe addition of thalidomide to chemoradiotherapy increased toxicities but did not improve survival in patients with locally advanced NSCLC.

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“…Local recurrence is a common clinical problem and is the primary contributor to the poor prognosis of a large number of patients [6]. One of the major reasons for local recurrence is the development of radiation resistance [7]. Therefore, clarification of the mechanism underlying radiation resistance and the establishment of a valid prognostic factor and therapeutic target are clinically important.…”

Standard Treatment Option in Stage III Non–Small-Cell Lung Cancer: Case Against Trimodal Therapy and Consolidation Drug Therapy

“…Decreased survival seemed as the result of tumor progression and not gefitinib toxicity. Finally, Hoang et al 56 reported on an Eastern Cooperative Oncology Group (ECOG) 3598 trial that tested the addition of thalidomide. Patients were randomly assigned to the control arm involving 2 cycles of induction paclitaxel and carboplatin (PC) followed by thoracic RT administered concurrently with weekly PC, or to the experimental arm (TPC), receiving the same treatment in combination with thalidomide.…”

Chemoradiotherapy of locally advanced nonsmall cell lung cancer

“…However, the development of tracheoesophageal fistulae in two phase II trials led to early closure of the trials [31]. Also, a randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III NSCLC did not show a clinical benefit for thalidomide [32]. Also, two trials of maintenance of gefitinib and erlotinib versus placebo failed to demonstrate an improved outcome with targeted therapies [33,34].…”