Continuous intravenous pumping (CIP) of recombinant human endostatin (Endostar) combined with concurrent radiochemotherapy in patients with unresectable stage III non-small-cell lung cancer: preliminary data of a prospective multicenter phaseIIclinical trial

Objective 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). Methods In this prospective study, patients with unresectable stage IIIA or IIIB NSCLC received CIP of Endostar (7.5 mg/m2) over 5 days at week 1, 3, 5, and 7.During week 2-8, patients received two 28-day cycles of etoposide 50 mg/m2 on day 1-5 and cisplatin 50 mg/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. Results Between Nov.2012 and Jun.2015, 63 patients were eligible for toxicity and efficacy evaluation, including 52(83%) male and 11(16%) female, 41(65%) with squamous cell carcinoma, 19(30%) with adenocarcinoma, 1(2%) with large cell carcinoma and 2(3%) with undifferentiated carcinoma, and 27(43%) with stageIIIA disease and 36(57%) with IIIB disease, respectively. The median age was 59(31-69) years. All patients completed the treatment as planned, except that 2 patient missed one cycle chemotherapy for unrecovered grade 2 renal function impairmentandgrade Ⅳ myelosuppression. There were 8(13%), 40(64%), 11(18%) and 4(6%) patients achieved complete response, partial response, stable disease and progressive disease, respectively. The objective remission rate (ORR) is 76%.There were 23 patients (37%) with grade 3+ 4 neutropenia, 9(14%) with grade 3+ 4 anemia, and 10(16%) with grade 3+ 4 thrombocytopenic. Two patients (5%) developed grade 3 nausea/vomiting. Grade 3 acute esophagitis, grade 1+ 2 and grade 3 pneumonitis were observed in 8(13%), 12(19%) and 2(3%) patients, respectively. No grade 2 cardiovascular toxicity was observed.Up to the last follow-up, the median follow-up time was 13.6 months.21 deaths were observed, including 15 died of cancer progression. The median PFS was 14.8 months. The 1-year PFS, OS was 51%, 78%, respectively. Conclusions 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 await further follow up. Clinical Trial Registry ClinicalTrials.gov, registration number: NCT01733589. Key words: Carcinoma, non-small cell lung/radiochemotherapy; Endostar; Short-term effect; Toxicity