Continuous Intravenous Pumping of Recombinant Human Endostatin Combined With Concurrent Chemoradiation Therapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer: Preliminary Data of a Prospective Multicenter Phase 1/2 Clinical Trial (NCT01733589) : Locally Advanced Non-Small Cell Lung Cancer

Purpose/Objective(s)Preclinical models have shown that recombinant human endostatin 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 of endostatin combined with standard concurrent chemoradiation therapy for unresectable stage III non-small cell lung cancer (NSCLC).Materials/MethodsIn this prospective study, patients with unresectable stage IIIA or IIIB NSCLC received continuous intravenous pumping of endostatin (7.5 mg/m2/d) over 5 days at weeks 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. Tumor response was evaluated using RECIST 1.1 criteria.ResultsBetween Nov. 2012 and Dec. 2013, 31 patients were enrolled into the study, including 28 (90.3%) male and 3 (9.7%) female, 22 (71.0%) with squamous cell carcinoma and 8 (25.8%) with adenocarcinoma, and 13 (41.9%) with stage IIIA disease and 18 (58.1%) with IIIB disease, respectively. The median age was 59 (43-69) years. One patient quit the study for the celiac lymph node metastasis, and the remaining 30 were eligible for toxicity and efficacy evaluation. All patients completed the treatment as planned, except that 1 patient missed one cycle chemotherapy for unrecovered grade 2 renal function impairment. There were 11 patients (36.7%) with grade 3/4 neutropenia, 5 (16.7%) with grade 3 anemia, and 4 (13.3%) with grade 3 thrombocytopenic. Three patients (10%) developed grade 3 nausea/vomiting. Grade 3 acute esophagitis and grade 1/2 pneumonitis were observed in 7 (23.3%) and 5 (16.7%) patients, respectively. No cardiovascular toxicity was observed. There were 19 (63.3%), 7 (23.3%), and 4 (13.3%) patients achieved partial response, stable disease, and progressive disease, respectively. Up to the last follow-up, 3 deaths were observed, including 2 died of cancer progression, and 1 died of hemoptysis 2 months after the completion of treatment who had right pulmonary artery invasion by tumor at the diagnosis.ConclusionsFor patients with unresectable stage III NSCLC, continuous intravenous pumping of endostatin combined with concurrent chemoradiation therapy is tolerable and the short term outcomes are promising. Long term survival data await further follow up. Purpose/Objective(s)Preclinical models have shown that recombinant human endostatin 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 of endostatin combined with standard concurrent chemoradiation therapy for unresectable stage III non-small cell lung cancer (NSCLC). Preclinical models have shown that recombinant human endostatin 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 of endostatin combined with standard concurrent chemoradiation therapy for unresectable stage III non-small cell lung cancer (NSCLC). Materials/MethodsIn this prospective study, patients with unresectable stage IIIA or IIIB NSCLC received continuous intravenous pumping of endostatin (7.5 mg/m2/d) over 5 days at weeks 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. Tumor response was evaluated using RECIST 1.1 criteria. In this prospective study, patients with unresectable stage IIIA or IIIB NSCLC received continuous intravenous pumping of endostatin (7.5 mg/m2/d) over 5 days at weeks 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. Tumor response was evaluated using RECIST 1.1 criteria. ResultsBetween Nov. 2012 and Dec. 2013, 31 patients were enrolled into the study, including 28 (90.3%) male and 3 (9.7%) female, 22 (71.0%) with squamous cell carcinoma and 8 (25.8%) with adenocarcinoma, and 13 (41.9%) with stage IIIA disease and 18 (58.1%) with IIIB disease, respectively. The median age was 59 (43-69) years. One patient quit the study for the celiac lymph node metastasis, and the remaining 30 were eligible for toxicity and efficacy evaluation. All patients completed the treatment as planned, except that 1 patient missed one cycle chemotherapy for unrecovered grade 2 renal function impairment. There were 11 patients (36.7%) with grade 3/4 neutropenia, 5 (16.7%) with grade 3 anemia, and 4 (13.3%) with grade 3 thrombocytopenic. Three patients (10%) developed grade 3 nausea/vomiting. Grade 3 acute esophagitis and grade 1/2 pneumonitis were observed in 7 (23.3%) and 5 (16.7%) patients, respectively. No cardiovascular toxicity was observed. There were 19 (63.3%), 7 (23.3%), and 4 (13.3%) patients achieved partial response, stable disease, and progressive disease, respectively. Up to the last follow-up, 3 deaths were observed, including 2 died of cancer progression, and 1 died of hemoptysis 2 months after the completion of treatment who had right pulmonary artery invasion by tumor at the diagnosis. Between Nov. 2012 and Dec. 2013, 31 patients were enrolled into the study, including 28 (90.3%) male and 3 (9.7%) female, 22 (71.0%) with squamous cell carcinoma and 8 (25.8%) with adenocarcinoma, and 13 (41.9%) with stage IIIA disease and 18 (58.1%) with IIIB disease, respectively. The median age was 59 (43-69) years. One patient quit the study for the celiac lymph node metastasis, and the remaining 30 were eligible for toxicity and efficacy evaluation. All patients completed the treatment as planned, except that 1 patient missed one cycle chemotherapy for unrecovered grade 2 renal function impairment. There were 11 patients (36.7%) with grade 3/4 neutropenia, 5 (16.7%) with grade 3 anemia, and 4 (13.3%) with grade 3 thrombocytopenic. Three patients (10%) developed grade 3 nausea/vomiting. Grade 3 acute esophagitis and grade 1/2 pneumonitis were observed in 7 (23.3%) and 5 (16.7%) patients, respectively. No cardiovascular toxicity was observed. There were 19 (63.3%), 7 (23.3%), and 4 (13.3%) patients achieved partial response, stable disease, and progressive disease, respectively. Up to the last follow-up, 3 deaths were observed, including 2 died of cancer progression, and 1 died of hemoptysis 2 months after the completion of treatment who had right pulmonary artery invasion by tumor at the diagnosis. ConclusionsFor patients with unresectable stage III NSCLC, continuous intravenous pumping of endostatin combined with concurrent chemoradiation therapy is tolerable and the short term outcomes are promising. Long term survival data await further follow up. For patients with unresectable stage III NSCLC, continuous intravenous pumping of endostatin combined with concurrent chemoradiation therapy is tolerable and the short term outcomes are promising. Long term survival data await further follow up.