Continuous Intravenous Pumping Endostar Combined with Radiochemotherapy in Unresectable Stage III Non-Small-Cell Lung Cancer

Preclinical models have shown that recombinant human endostatin (Endostar) can transiently normalize the tumor vasculature to make it more efficient for oxygen delivery, which provides a treatment window of enhancing tumor radiosensitivity. This study is to evaluate the safety and efficacy of continuous intravenous pumping (CIP) of Endostar combined with standard concurrent radiochemotherapy for unresectable stage III non-small-cell lung cancer (NSCLC). In this prospective study, patients with unresectable stage IIIA or IIIB NSCLC received CIP of Endostar (7.5mg/m2) over 5 days at weeks 1, 3, 5, and 7. During week 2-8, patients received two 28-day cycles of etoposide 50mg/m2 on day 1-5 and cisplatin 50mg/m2 on day 1, 8, with concurrent thoracic radiation of 60-66 Gy in 30-33 fractions over 6-7 weeks. Acute toxicities were evaluated using CTCAE 3.0. Tumor response was evaluated using RECIST 1.1 criteria. Between Nov. 2012 and May. 2016, 67 patients were eligible for toxicity and efficacy evaluation, including 56 (83.6%) male and 11 (16.4%) female, 44 (65.7%) with squamous cell carcinoma, 20(29.9%) with adenocarcinoma, 1 (1.5%) with large cell carcinoma and 2 (3.0%) with undifferentiated carcinoma, and 28 (41.8%) with stage III A disease and 39 (58.2%) with III B disease, respectively. The median age was 59 (31-69) years. All patients completed the treatment as planned, except that 3 patient missed one cycle chemotherapy. There were 8 (11.9%), 43 (64.2%), 11 (16.4%) and 4 (6.0%) patients achieved complete response, partial response, stable disease and progressive disease, respectively. The objective remission rate (ORR) is 76.1%. There were 23 patients (34.3%) with grade 3+4 neutropenia, 9 (13.4%) with grade 3+4 anemia, and 10 (14.9%) with grade 3+4 thrombocytopenic. Three patients (4.5%) developed grade 3 nausea/vomiting. Grade 3 acute esophagitis, grade 1+2 and grade 3 pneumonitis were observed in 8 (11.9%), 12 (17.9%) and 2 (3.0%) patients, respectively. One patient died of pneumonitis before efficacy evaluation. No grade 2 cardiovascular toxicity was observed. Up to the last follow-up, the med. For patients with unresectable stageIII NSCLC, CIP of Endostar enhanced patient compliance, and combined with concurrent radiochemotherapy is tolerable and the short term outcomes are promising. Long term survival data wait further follow up.