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.
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico; Experimental Oncology Laboratory, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico. Electronic address: ogar@unam.mx.
Oscar
O
Arrieta
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
Mónika
M
Blake
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
María Dolores
MD
de la Mata-Moya
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
Francisco
F
Corona
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
Jenny
J
Turcott
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
David
D
Orta
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
Jorge
J
Alexander-Alatorre
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
Dolores
D
Gallardo-Rincón
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D060830:Consolidation Chemotherapy / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000009:adverse effects / Q000627:therapeutic use*; D005996:Nitroglycerin / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
D020030:Nitric Oxide Donors; D042461:Vascular Endothelial Growth Factor A; D014747:Vinblastine; D005996:Nitroglycerin; D002945:Cisplatin; D000077235:Vinorelbine
Chemo-radiotherapy; Locally advanced; Nitroglycerin; Non-small cell lung cancer