Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma.

Abstract

PURPOSE:

Nitroglycerin may improve the response to chemotherapy in advanced non-small cell lung cancer. The effects and mechanisms of nitroglycerin on the enhancement of chemosensitivity to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma have not been reported.

EXPERIMENTAL DESIGN:

Seventeen patients with operable lung adenocarcinoma and stable angina pectoris were selected to investigate the effects of nitroglycerin on immunoreactivity for hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), P-glycoprotein (P-gp), the production of which is regulated by HIF-1, and p53 proteins in their resected tumor by semiquantitative immunohistochemical analyses. Eight of 17 patients were treated with nitroglycerin patches before operation, but 9 of 17 patients were not. Furthermore, to study the relationship between changes in plasma VEGF levels by nitroglycerin treatment and response to DCb, 29 patients with advanced lung adenocarcinoma were treated with nitroglycerin for 3 days before chemotherapy using DCb.

RESULTS:

The rates of immunoreactive cells for HIF-1alpha, VEGF, and P-gp in tumor tissues treated with nitroglycerin were lower than those without nitroglycerin, but those for p53 were not different between those treated with and without nitroglycerin. Furthermore, the rates of immunoreactive cells for VEGF and P-gp proteins were significantly associated with those for HIF-1alpha in tumor tissue. The magnitude of decrease in plasma VEGF levels after treatment with nitroglycerin was significantly associated with response to DCb in patients with advanced lung adenocarcinoma.

CONCLUSIONS:

Nitroglycerin treatment may improve response to DCb in patients with lung adenocarcinoma, partly through decreasing VEGF and P-gp production via reduction of HIF-1alpha.

• Authors: Hiroyasu Yasuda, Katsutoshi Nakayama, Mika Watanabe, Satoshi Suzuki, Hiromi Fuji, Shoji Okinaga, Akio Kanda, Kiyoshi Zayasu, Takahiko Sasaki, Masanori Asada, Tomoko Suzuki, Motoki Yoshida, Shinsuke Yamanda, Daisuke Inoue, Tomohiro Kaneta, Takashi Kondo, Yoshihiro Takai, Hidetada Sasaki, Kazuhiro Yanagihara, Mutsuo Yamaya
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 12 Issue 22 Pg. 6748-57 (Nov 15 2006) ISSN: 1078-0432 [Print] United States
• PMID: 17121895 (Publication Type: Controlled Clinical Trial, Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Taxoids
• Tumor Suppressor Protein p53
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Docetaxel
• Carboplatin
• Nitroglycerin

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Adenocarcinoma (drug therapy, metabolism, surgery)
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carboplatin (administration & dosage, adverse effects)
• Combined Modality Therapy (adverse effects)
• Disease Progression
• Docetaxel
• Drug Resistance, Neoplasm (drug effects)
• Female
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Lung Neoplasms (drug therapy, metabolism, surgery)
• Male
• Middle Aged
• Nitroglycerin (administration & dosage, adverse effects, pharmacology)
• ROC Curve
• Taxoids (administration & dosage, adverse effects)
• Tumor Suppressor Protein p53 (metabolism)
• Vascular Endothelial Growth Factor A (blood, metabolism)