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

7068 Background: The treatment of choice for locally advanced non small cell lung cancer (NSCLC) is concurrent chemoradiation (CRT). However, efforts to improve treatment results include targeted therapy and the use of radiosensitizers. Nitroglycerin (NTG), a nitric oxide (NO) donor agent, reduces expression of Hypoxia-Induced Factor, which is associated to both chemo and radio resistance. Methods: This is phase II trial in patients with locally advanced NSCLC treated with chemotherapy (CT) based on cisplatin and vinorelbin with NTG concurrent with radiation therapy. A 25 mg NTG patch was administered to the patients during the first 5 days of each induction treatment cycle and during chemo-radiotherapy. Blood samples of VEGF were taken before any treatment and after two cycles of CT. The protocol is registered with ClinicalTrials.gov, number NCT00886405. Results: 35 patients were enrolled in this trial. Median Follow up was 16.6 months (SD ±13.6). Mean age was of 59.9 years (±10.8), 68.6% of the patients were smokers. ECOG status was 0 in 22.9%, 1 in 65.7% and 2 in 11.5%, respectively. Histopathology was adenocarcinoma in 68.6%, epidermoid in 17.1% and undifferentiated in 14.3%. Stage distribution was: IIIa, 57.6% and IIIb, 42.5%. All patients completed CRT treatment and four underwent surgical treatment. Toxicity profile related to NTG was grade 1 and 2 headache in 17.1%. Grade 3 and 4 toxicities were esophagitis (17.1%), neutropenia (62.9%), and nausea (5.7%). Sixty-four per cent of patients achieved partial response after CT and 75.8% after CRT. PFS was 11.8 months (95%, IC 7.8-15.6) and OS was 42.9 months (95%IC 31.3-52.1). After two cycles of CT, plasma VEGF levels were significantly lower (Median 132±79 vs. 53±78 pg/ml, p<0.001). No differences on PFS and OS were found between patients with a reduction ≥ 93 pg/ml (median of differences between VEGFR before and after chemotherapy). Conclusions: The addition of NTG to induction CT, and concurrent CRT on locally advanced NSCLC patients seems to increase the response rate, PFS and OS with an acceptable toxicity profile. A prospective trial is warranted to confirm these findings.