{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T13:34:26Z","timestamp":1768829666363,"version":"3.49.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Lessons Learned<\/jats:title>\n                  <jats:p>Melatonin did not increase the efficacy of systemic chemotherapy in melanoma. Metformin did not increase the efficacy of systemic chemotherapy in melanoma.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Current data support the possibility of antitumor activity of melatonin and metformin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>ORR was 7% and did not differ among the treatment groups. Median TTP was 57, 57, and 47\u2009days, respectively, in the first, second, and third groups (\u0440\u2009=\u2009.362). Median OS was 236, 422, and 419\u2009days, respectively (p\u2009=\u2009.712). Two patients from the combinations groups showed delayed response to therapy. The increase of CD3+CD4+HLA-DR+ lymphocytes (p\u2009=\u2009.003), CD3+CD8+HLA-DR+ (p\u2009=\u2009.045), CD3+CD8+ lymphocytes (p\u2009=\u2009.012), CD4+CD25highCD127low lymphocytes (p\u2009=\u2009.029), and overall quantity of lymphocytes (p\u2009=\u2009.021) was observed in patients with clinical benefit.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/onco.13761","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T04:06:07Z","timestamp":1616385967000},"page":"364-e734","source":"Crossref","is-referenced-by-count":11,"title":["Melatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma"],"prefix":"10.1093","volume":"26","author":[{"given":"Aleksei Viktorovich","family":"Novik","sequence":"first","affiliation":[{"name":"Department of Oncoimmunology, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia"},{"name":"Department of Oncology, Child Oncology and Ray Therapy, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana Anatolievna","family":"Protsenko","sequence":"additional","affiliation":[{"name":"Department of Chemotherapy and Innovative Technologies, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina Alexandrovna","family":"Baldueva","sequence":"additional","affiliation":[{"name":"Department of Oncoimmunology, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lev Michailovich","family":"Berstein","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, N.N. 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