PUB108 Concurrent Nab-Paclitaxel/Carboplatin Combined with Thoracic Radiotherapy in Locally Advanced Squamous Cell Lung Cancer (NCT01494415)

Abstract

Chemoradiotherapy is the standard treatment for locally advanced squamous cell lung cancer, however, treatment development is urgently needed due to poor prognosis and significant toxicity. Combination therapy of carboplatin and nab-paclitaxel is a useful choice as first-line therapy for patients with advanced non-small cell lung cancer, especially for squamous cell cancer. This prospective phase II study was conducted to explore the efficacy and toxicity of concurrent chemoradiotherapy with nab-paclitaxel, carboplatin and thoracic radiotherapy in unresectable locally advanced squamous cell lung cancer. Patients with unresectable Stage III squamous cell lung cancer were eligible. Patients received nab-paclitaxel weekly at a dose of 60mg/m2, in combination with carboplatin (area under the plasma concentration time curve (AUC) 2) weekly during concurrent chemoradiotherapy. Thoracic radiation was administered at a dose of 66Gy/33 fractions, both three dimensional conformal and intensity modulated radiation therapy were allowed. The consolidation phase chemotherapy consisted of full dose nab-paclitaxel (260 mg/m2 on day 1) and carboplatin (AUC 6 on day 1) every 21 days was administered in two cycles after the concurrent chemoradiotherapy. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), acute radiation esophagitis and pneumonitis.(Clinical trial registration: NCT01494415). Initially, enrollment of 21 patients was planned; however, the trial was prematurely closed due to slow recruitment. Finally, a total of 8 patients were enrolled between January 2012 and July 2015 from one institute. All patients completed concurrent chemoradiotherapy and 6 patients (75.0%) received consolidation chemoradiotherapy. The objective response rate was 62.5%, with partial remission 5 (62.5%), stable disease 2 (25.0%), progressive disease 1 (12.5%), respectively. After a median follow-up of 11.6 (range, 2.0–29.2) months, 5 patients were dead, 3 were alive. The median progression-free survival and overall survival were 12.1 months and 15.2 months, respectively. According to Common Terminology Criteria for Adverse Events (CTCAE) version.4.0, 6 patients (75.0%) experienced acute radiation esophagitis, 4 (50.0%) were grade 2 (G2), 2 (25.0%) were G3; 4 patients (50%) experienced acute radiation pneumonitis, 3 (37.5%) were G2, 1 (12.5%) were G3. No late radiation-induced esophageal and pulmonary toxicity was observed after 1-year follow-up. Concurrent nab-paclitaxel, carboplatin and thoracic radiotherapy is showed to be an effective regimen for patients with unresectable locally advanced squamous cell lung cancer. However, further study should exercise caution due to the severe toxicity of radiation tissue injury especially acute radiation esophagitis.