Radical consolidative treatment provides a clinical benefit and long-term survival in patients with synchronous oligometastatic non-small cell lung cancer: A phase II study.

OBJECTIVES: Evidence is rapidly accumulating for the use of radical consolidative treatment (RCT) for patients with oligometastatic non-small cell lung cancer (NSCLC). Nonetheless, published studies have several limitations, including a selection of patients whose favorable characteristics might dictate therapeutic success, as well as scarce prospective data regarding overall survival (OS). The objective of this study was to determine whether RCT increases OS in patients with oligometastatic NSCLC. MATERIALS AND METHODS: In this prospective, single-arm phase II study, we sought to evaluate the efficacy of RCT in patients with oligometastatic NSCLC in terms of OS. Patients with pathologically confirmed stage IV NSCLC who presented ≤5 synchronous, any-site metastases (including central nervous system [CNS] metastases), as assessed by PET-CT, were included. All patients received four initial cycles of systemic treatment. Following, those with stable disease/partial response received RCT to the primary site and metastases. The response to RCT was evaluated with PET-CT. The primary end-point was OS. Secondary end-points included progression-free survival (PFS) and best response by PET-CT. The study is registered in clinicaltrials.gov (NCT02805530). RESULTS: Thirty-seven patients were included in the analysis. The mean age was 55.8 years (range: 33-75 years). At diagnosis, 43.2% of patients presented with CNS metastases. Following RCT, 19 (51.4%) patients achieved a complete-response (CR) by PET-CT, while 18 (48.6%) had a non-complete response (NON-CR). The median OS was nonreached (NR) and was positively affected by CR on PET-CT (NR vs. 27.4 [95% CI: 16.4-38.3]; p = 0.011). The median PFS was 23.5 months (95% CI: 13.6-33.3) and was positively affected by CR on PET-CT (NR vs. 14.3 [95% CI: 11.7-16.9]; p < 0.001; HR: 0.19 [0.07-0.52]; p=0.001). CONCLUSION: Patients with oligometastatic NSCLC who undergo RCT have a high response rate and favorable OS. Patients with a CR by PET-CT have significantly longer OS, rendering this an important potential prognostic marker.

Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer.

BACKGROUND: Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). METHODS: This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. RESULTS: Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8-18.2), and the median overall survival was 26.9 months (95% CI, 15.3-38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). CONCLUSIONS: The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings.