Open AccessMelatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma
Author(s) -
Novik Aleksei Viktorovich,
Protsenko Svetlana Anatolievna,
Baldueva Irina Alexandrovna,
Berstein Lev Michailovich,
Anisimov Vladimir Nikolaevich,
Zhuk Iriikolaevna,
Semenova Anna Igorevna,
Latipova Dilorom Khamidovna,
Tkachenko Elena Viktorovna,
Semiglazova Tatiana Yurievna
Publication year - 2021
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1002/onco.13761
Subject(s) - medicine , dacarbazine , melatonin , metformin , melanoma , chemotherapy , clinical endpoint , immune system , cd8 , oncology , gastroenterology , pharmacology , immunology , clinical trial , cancer research , insulin
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/m 2 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 + CD25 high CD127 low 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.