DIPYRIDAMOLE

Clinical research on dipyridamole in cancer has shown a lack of results, and some studies were terminated early due to side effects of the drug. Older trials in advanced breast and colon cancers reported no significant benefits even when there was some evidence of response. A more recent meta-analysis of colorectal cancer cases has shown patient data indicating the combination of aspirin with dipyridamole reduces relative mortality risk more than either drugs alone.

Dipyridamole is a drug used to treat coronary and peripheral artery disease. It reduces clots and dilates blood vessels. Its worth noting there are several functional foods and supplements able to achieve these actions without the need for drugs adn the inevitable side effects. So the idea of using something like dipyridamole can only have any value if it comes from your oncologist. Direct your own efforts to improve crucial markers of vascular health to our Supplements and Foods Libraries. Combinations including nattokinase with low dose aspirin or red yeast rice have impressive effects. Get similar results whilst improving your gut microbiome, reducing inflammation and improving metabolism.

The concept of using multiple re-purposed drugs for so called metabolic cancer therapy has included mebendazole with metformin, atorvastatin, dipyridamole and doxycycline. This has been withdrawn from its phase 3 trials, due to a lack of benefit and high burden from side effects in patients; https://clinicaltrials.gov/study/NCT02201381 [also noted under metformin and mebendazole]. With the obvious exception of atorvastatin, these drugs have in most cases more potential to damage oncology results than help.

We found that dipyridamole combined with aspirin had a better inhibitory effect on CRC than either monotherapy alone. The enhanced anti-cancer effect of the combined use of dipyridamole with aspirin was found to rely on the induction of an overwhelmed endoplasmic reticulum (ER) stress and subsequent pro-apoptotic unfolded protein response (UPR), which was different from the anti-platelet effect…Our data indicate that the anti-cancer effect of aspirin against CRC may be enhanced by combined administration with dipyridamole. In case further c...

According to the response achieved at Dose Schedule III (15% partial response and 45% stable disease) and the toxicity which was well tolerated mainly in this DS..In conclusion, it appears that dipyridamole might still have a role in enhancing the clinical activity of drugs involved in the inhibition of the thymidylate synthetase biochemical pathway and its activity in combination with these agents (5-fluorouracil + leucovorin) as frontline treatment should therefore be explored in future phase II studies.

The pharmacokinetics of DP was studied in three patients; the results showed that 98% of total serum DP was protein-bound and that free DP levels were significantly lower than the concentrations necessary for the expected in vitro DP/FUDR modulation. Treatment was well tolerated, with only 12 patients developing mild to moderate toxicity. Of 27 evaluable patients, 4 achieved a partial response that lasted 2, 3, 5, and 6+ months. This relatively low response rate (15%), which is similar to that achieved with FUDR alone

Unacceptable toxicity was observed at this dose level, leading to successive dose decrements rather than dose increments. The maximum tolerated dose was leukovorin 200 mg/m2 days 1–2, 5-FU 375 mg/m2 days 1–2, mitoxantrone 6 mg/m2 on day 2, and dipyridamole 175 mg/m2 every 6 h on days 0–3. Two responses were produced in 15 patients. This regimen is not recommended for further investigation in the treatment of breast cancer.

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https://portal.research.lu.se/en/publications/dipyridamole-enhances-the-anti-cancer-ability-of-aspirin-against-	3	The enhanced anti-cancer effect of the combined use of dipyridamole with aspirin was found to rely on the induction of an overwhelmed endoplasmic reticulum (ER) stress and subsequent pro-apoptotic unfolded protein response (UPR), which was different from the anti-platelet effect	Our data indicate that the anti-cancer effect of aspirin against CRC may be enhanced by combined administration with dipyridamole. In case further clinical studies confirm our findings, these may be repurposed as adjuvant agents.
https://journals.sagepub.com/doi/abs/10.1177/030089160108700505	2	According to the response achieved at Dose Schedule III (15% partial response and 45% stable disease) and the toxicity which was well tolerated mainly in this DS..In conclusion, it appears that dipyridamole might still have a role in enhancing the clinical activity of drugs involved in the inhibition of the thymidylate synthetase biochemical pathway and its activity in combination with these agents (5-fluorouracil + leucovorin) as frontline treatment should therefore be explored in future phase II studies.	No patient at DS I responded, whereas 2 patients at DS II and 3 at DS III had a partial response (P <0.1). Stable disease was found with DS I (n = 1), DS II (n = 8) and DS III (n = 9) (P <0.01). More patients progressed at DS I (n = 19) than at DS II (n = 10) and DS III (n = 8) (P <0.0007). The median duration of response was 11 weeks (range, 8-16). Time to progression was 17 weeks for DS I, 15 weeks (range, 10-19) for DS II, and 14 weeks (range, 11-21) for DS III (P = 0.43). Median survival did not differ significantly between DS I (29 weeks; range, 14-48), DS II (31.5 weeks; range, 17-63) and DS III (36 weeks)
https://pubmed.ncbi.nlm.nih.gov/7775128/	2	Unacceptable toxicity was observed at this dose level, leading to successive dose decrements rather than dose increments. The maximum tolerated dose was leukovorin 200 mg/m2 days 1–2, 5-FU 375 mg/m2 days 1–2, mitoxantrone 6 mg/m2 on day 2, and dipyridamole 175 mg/m2 every 6 h on days 0–3. Two responses were produced in 15 patients. This regimen is not recommended for further investigation in the treatment of breast cancer.	we performed a phase I/II trial of the combination of dipyridamole, 5-FU, leukovorin, and mitoxantrone in patients with metastatic breast cancer. The dose of dipyridamole was fixed at 175 mg/m2 by mouth every 6 h (700 mg/m2/day), based upon a previous phase I trial of oral dipyridamole with 5-FU and leukovorin. Dipyridamole therapy began 24 h prior to the first dose of chemotherapy and continued until 24 h after the last dose of chemotherapy for each course of treatment. At the initial dose level, leukovorin 200 mg/m2 was given intravenously immediately prior to 5-FU 375 mg/ m2 intravenously on days 1–5.
https://link.springer.com/article/10.1007/BF00692352	2	Treatment was well tolerated, with only 12 patients developing mild to moderate toxicity. Of 27 evaluable patients, 4 achieved a partial response that lasted 2, 3, 5, and 6+ months. This relatively low response rate (15%), which is similar to that achieved with FUDR alone, may be explained by the low steady-state plasma concentrations of free DP achieved in our patients. Other means of DP administration, such as i.v., i.a., and i.p. injection, may be required to achieve free DP concentrations	28 patients with metastatic colon cancer were entered in a clinical trial of monthly courses of 0.1 mg/kg FUDR daily for 14 days and 75 mg oral DP 5 times daily for 14 days starting on the 3rd day of continuous i.v. FUDR infusion. The pharmacokinetics of DP was studied in three patients; the results showed that 98% of total serum DP was protein-bound and that free DP levels were significantly lower than the concentrations necessary for the expected in vitro DP/FUDR modulation
https://ascopubs.org/doi/10.1200/JCO.1995.13.5.1201	N/A	Orally administered DP did not improve the antineoplastic activity of 5-FU/FA in patients with advanced colorectal cancer when used at this dose and schedule. The observed increase in 5-FU dose-intensity for FU/FA/DP was not clinically relevant.	The dose-intensity of 5-FU delivered was significantly higher (1.09- to 1.16-fold) for the DP-containing arm. Pharmacokinetic parameters of 5-FU did not differ significantly, except for a prolonged half-life (t1/2) induced by DP. The median time to progression (P = .8) and the median survival time (11.6 months for 5-FU/FA v 9.3 months for 5-FU/FA/DP; P = .14, log-rank test) were not different between treatment arms.
https://journals.lww.com/amjclinicaloncology/abstract/2000/10000/phase_ii_evaluation_of_continuous_infusion.21.aspx	N/A	Although some patients did respond, the therapeutic results are not encouraging enough to take this regimen to phase III testing	Of 46 evaluable patients, 9 partial responses and 1 complete tumor response were seen, for an overall response rate of 22% (95% confidence interval 11–36%). The median survival in the group of 50 patients registered to this trial was 4.6 months, with a range of 0.33 to 40.2 months

DIPYRIDAMOLE

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