Table 2.
Clinical Studies involving NO donors and Cancer.
| Completed Clinical Studies | |||||
|---|---|---|---|---|---|
| NO Drug | Cancer Type | Combination Treatment | Compared with | Effect | Reference |
| Transdermal Nitroglycerin |
Stage IV NSCLC | Paclitaxel, carboplatin, and bevacizumab | Combination treatment minus nitroglycerin | Increased response rate in the nitroglycerin group. Increased overall survival and progression-free survival in nitroglycerin group that did not reach statistical significance |
[232] |
| Transdermal Nitroglycerin |
Stage III/IV NSCLC | Vinorelbine and cisplatin | Combination treatment minus nitroglycerin | 30% higher response rate in those treated with transdermal nitroglycerin and longer time to disease progression | [226] |
| Transdermal Nitroglycerin |
Stage IIIB/IV NSCLC | Vinorelbine and cisplatin | Combination treatment minus nitroglycerin | Higher overall response rate and disease control rate in nitroglycerin arm. Time to progression and overall survival were similar |
[233] |
| Transdermal Nitroglycerin |
Stages IIIA and IIIB NSCLC | Vinorelbine and cisplatin and radiotherapy | None: Non-randomized |
75% overall response rate after chemotherapy and radiotherapy. Median progression-free survival of 13.5 months (95% CI, 8.8–18.2), while the median overall survival was 26.9 months | [230] |
| Transdermal Nitroglycerin |
PSA recurrent prostate cancer after definitive radiotherapy or radical prostatectomy | N/A | N/A | The mean PSA doubling time of the entire cohort increased to 31.8 months from 13.2 months before starting treatment |
[228] |
| Transdermal Nitroglycerin |
Operable clinical stage T3-4, or T1-4 node-positive, M0 rectal adenocarcinoma |
5-fluorouracil and radiation therapy prior to surgery | None: Phase I Trial | Pathological Complete response of 17%. Only one patient experienced side effects attributed to nitroglycerin | [229] |
| IV Nitroglycerin | Barcelona clinic liver cancer stage A/B hepatocellular carcinoma |
Doxorubicin emulsified in Lipiodol followed by Transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization (TACE) | Combination treatment minus nitroglycerin | Greater change in lesion size from baseline was observed for nitroglycerin group. Nitroglycerin therapy group showed higher concentration of lipiodol (and thus chemotherapeutic) inside the lesion. |
[227] |
| Isosorbide mononitrate |
Stage IIIB/IV NSCLC | Irinotecan plus cisplatin and Irinotecan plus capecitabine | Combination treatment minus Isosorbide mononitrate |
Isosorbide mononitrate addition did not improve outcomes to either treatment group |
[234] |
| Isosorbide mononitrate |
T1-T4 Oral Squamous Cell Carcinoma |
Surgery after drug administration |
Surgery alone | No difference in Ki-67 tumor staining was noted | [235] |
| Ongoing Clinical Studies without Posted Results | |||||
| Drug | Cancer Type | Combination Treatment | Compared with | Completed | Clinical Trial Number |
| Transdermal Nitroglycerin | NSCLC with brain metastases | Whole brain radiation | Combination treatment minus nitroglycerin | Yes | NCT04338867 |
| IV Nitroglycerin | Pediatric Retinoblastoma | Intra-arterial chemotherapy |
Normal Saline and combination treatment | No | NCT04564521 |
| Dietary Arginine | Colon Cancer | Nutritional Supplement Prior to Surgery | Surgery alone | Yes | NCT04564521 |
| Dietary Arginine | Stage III/IV Head and Neck Cancer | omega-3 fatty acids and nucleotides oral supplement with cisplatin and radiation therapy |
Cisplatin and radiation alone |
Yes | NCT00559156 |
| Dietary Arginine | Bladder Cancer | Radical cystoscopy | Radical cystoscopy alone |
Yes | NCT02655081 |
| Dietary Arginine | unresectable metastatic brain tumors |
Radiation | Radiation alone | Yes | NCT02844387 |
| Nicorandil | stage II—IV NSCLC | Radiation | Radiation alone | Unknown | NCT02809456 |
N/A: No additional treatment.