Induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone for unresectable stage III non-small cell lung cancer (NSCLC): Randomized phase III trial

Abstract

7528 Background: We conducted a prospective randomized phase III trial comparing induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) versus immediate CCRT to evaluate whether the addition of induction chemotherapy would result in improved survival. Methods: Patients with unresectable stage III NSCLC, ECOG PS 0–1, and weight loss up to 10% were eligible. They were randomized to receive either induction chemotherapy followed by CCRT (arm A) or immediate CCRT (arm B) after stratification for stage (T4N0–2, T1–3N3, T4N3, and stage IIIA), histology (squamous vs non-squamous), and SCLN positivity. Induction chemotherapy consisted of two cycles of gemcitabine (1,000 mg/m2 D1, D8) and cisplatin (70 mg/m2 D1) q 21days. Chemotherapy during CCRT consisted of 6 cycles of weekly paclitaxel (50 mg/m2) and cisplatin (20 mg/m2). Radiation therapy performed with hypofractionated scheme (2.2 Gy/fraction, once a day) and total dose was 66 Gy. Irradiated volume encompassed gross tumor plus 1.0 cm margin. Results: Between March 2003 and June 2006, 134 patients were enrolled. 92% of patients were male and 60% were age 60 or older. Objective tumor response was obtained in 38% after induction chemotherapy. Response rates after completion of CCRT were 72% (95% CI, 61%–83%) on arm A and 79% (95% CI, 69%–89%) on arm B. Grade 3/4 toxicities during induction chemotherapy consisted mainly of neutropenia (11%/3%). During CCRT, grade 3/4 neutropenia was noted in 8%/5% (arm A) versus in 8%/0% (arm B), grade 3 anemia was 8% vs 0%, grade 3 thrombocytopenia 5% vs 0%, and grade 3 esophagitis 16% vs 16%. At median follow-up of 28 months, median survival was 12.6 months (95% CI, 8.6–16.7 months) on arm A versus 18.2 months (95% CI, 11.7–24.8 months) on arm B (P=0.18). Two year survival estimates was 25% (15%–35%) and 43% (31%–55%), respectively. Median progression free survival was 7.5 months (95% CI, 5.6–9.4 months) on arm A and 11.6 months (95% CI, 9.6–13.6 months) on arm B (P=0.04). Conclusions: The addition of induction chemotherapy to CCRT failed to increase the survival of unresectable stage III NSCLC over immediate CCRT. Moreover, the progression free survival was inferior to immediate CCRT. No significant financial relationships to disclose.

Long-Term Results of a Phase II Trial of Induction Paclitaxel-Carboplatin Followed by Concurrent Radiation Therapy and Weekly Paclitaxel and Consolidation Paclitaxel-Carboplatin in Stage III Non-small Cell Lung Cancer

“…Despite these poor prognostic features, the median survival was 16.9 months, and the 5-year survival and 10-year survival were 25% and 17.5%, respectively. These results are similar to the best results of previous phase III trials of concurrent versus sequential RT-CHT, 9 -11 those of the phase III induction CHT and RT-CHT, [12][13][14] and those of the consolidation CHT therapy after concurrent RT-CHT. 15 The toxicity, albeit significant (one grade 5), was manageable and was diminished compared with that of a previous trial, 3 thereby confirming our previous hypothesis.…”

Stage III Non–Small-Cell Lung Cancer Treated With Concurrent Chemoradiation Followed or Not by Consolidation Chemotherapy: A Survival Analysis From a Brazilian Multicentric Cohort

“… 14 More recently, a meta-analysis of published data from seven phase III and 34 phase II randomized trials did not show improvement in OS associated with CC after CCRT for patients with LA-NSCLC. 15 Similarly, the addition of neoadjuvant chemotherapy 16 , 17 or neoadjuvant chemotherapy plus CC 18 to CCRT did not improve OS.…”

Long-Term Follow-Up of a Phase I/II Trial of Dose Escalating Three-Dimensional Conformal Thoracic Radiation Therapy with Induction and Concurrent Carboplatin and Paclitaxel in Unresectable Stage IIIA/B Non-small Cell Lung Cancer

“…Furthermore, phase III trials that have compared the treatment strategy of induction chemotherapy followed by concurrent chemotherapy versus concurrent chemoradiotherapy have not revealed a statistically significant survival benefit with the addition of induction chemotherapy. 19,30 It is possi- ble that modification of the chemotherapy platform or the addition of a targeted agent may have greater efficacy provided that the combination had acceptable toxicity and did not compromise the delivery of the high dose TCRT.…”