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. 2021 May;26(5):364-e734.
doi: 10.1002/onco.13761. Epub 2021 Apr 9.

Melatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma

Aleksei Viktorovich Novik  1   2 , Svetlana Anatolievna Protsenko  3 , Irina Alexandrovna Baldueva  1 , Lev Michailovich Berstein  4 , Vladimir Nikolaevich Anisimov  5 , Irina Nikolaevna Zhuk  6 , Anna Igorevna Semenova  3 , Dilorom Khamidovna Latipova  3 , Elena Viktorovna Tkachenko  6 , Tatiana Yurievna Semiglazova  3
Affiliations

Melatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma

Aleksei Viktorovich Novik et al. Oncologist. 2021 May.

Abstract

Lessons learned: Melatonin did not increase the efficacy of systemic chemotherapy in melanoma. Metformin did not increase the efficacy of systemic chemotherapy in melanoma.

Background: Current data support the possibility of antitumor activity of melatonin and metformin.

Methods: From March 2014 to December 2016, 57 patients with disseminated melanoma received dacarbazine (DTIC) 1,000 mg/m2 on day 1 of a 28-day cycle, either as monotherapy (first group) or in combination with melatonin 3 mg p.o. daily (second group) or metformin 850 mg two times a day p.o. daily (third group) as the first-line of chemotherapy. The primary endpoint was objective response rate (ORR). Secondary endpoints were time to progression (TTP), overall survival (OS), immunologic biomarkers, and quality of life.

Results: ORR was 7% and did not differ among the treatment groups. Median TTP was 57, 57, and 47 days, respectively, in the first, second, and third groups (р = .362). Median OS was 236, 422, and 419 days, respectively (p = .712). Two patients from the combinations groups showed delayed response to therapy. The increase of CD3+ CD4+ HLA-DR+ lymphocytes (p = .003), CD3+ CD8+ HLA-DR+ (p = .045), CD3+ CD8+ lymphocytes (p = .012), CD4+ CD25high CD127low lymphocytes (p = .029), and overall quantity of lymphocytes (p = .021) was observed in patients with clinical benefit.

Conclusion: No benefit was found in either combination over DTIC monotherapy. Delayed responses in melatonin and metformin combination groups were registered. The increase of lymphocyte subpopulations responsible for antitumor immune response demonstrates the immune system's potential involvement in clinical activity.

Trial registration: ClinicalTrials.gov NCT02190838.

Keywords: Dacarbazine; Melanoma; Melatonin; Metformin.

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References

    1. Pasquali S, Chiarion‐Sileni V, Rossi C et al. Immune checkpoint inhibitors and targeted therapies for metastatic melanoma: A network meta‐analysis. Cancer Treat Rev 2017;54:34–42. - PubMed
    1. Miller SC, Pandi‐Perumal SR, Esquifino AI et al. The role of melatonin in immuno‐enhancement: Potential application in cancer. Int J Exp Pathol 2006;87:81–87. - PMC - PubMed
    1. Li D. Metformin as an antitumor agent in cancer prevention and treatment. J Diabetes 2011;3:320–327. - PubMed
    1. Pierotti MA, Berrino F, Gariboldi M et al. Targeting metabolism for cancer treatment and prevention: Metformin, an old drug with multi‐faceted effects. Oncogene 2013;2:1475–1487. - PubMed
    1. Vazquez‐Martin A, Oliveras‐Ferraros C, Del Barco S et al. If mammalian target of metformin indirectly is mammalian target of rapamycin, then the insulin‐like growth factor‐1 receptor axis will audit the efficacy of metformin in cancer clinical trials. J Clin Oncol 2009;27:207–209; author reply e210. - PubMed

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