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British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Jun;80(7):1058–1061. doi: 10.1038/sj.bjc.6690463

Double-blind randomized study on the myeloprotective effect of melatonin in combination with carboplatin and etoposide in advanced lung cancer

M Ghielmini 1, O Pagani 1, J de Jong 1, S Pampallona 3, A Conti 2, G Maestroni 2, C Sessa 1, F Cavalli 1
PMCID: PMC2363039  PMID: 10362116

Abstract

A significant myeloprotective effect of melatonin in mice treated with etoposide, cyclophosphamide or carboplatin has been reported. The present study was designed to evaluate if the same effect could be observed in patients receiving chemotherapy. Twenty previously untreated patients with inoperable lung cancer received two cycles of carboplatin (given at area under the curve 5 by the Calvert formula) on day 1 and etoposide (150 mg m−2 i.v.) on days 1–3 every 4 weeks. Melatonin 40 mg or placebo (double-blind) was given orally in the evening for 21 consecutive days, starting 2 days before chemotherapy. Patients were randomized to receive melatonin either with the first or the second cycle. Complete blood cell count with differential was done three times per week for 3 weeks. The median age of the cohort was 60 years (range 42–69), 16 patients had non-small cell and four patients small-cell lung cancer, 12 stage III and eight stage IV disease. In a multivariate analysis including age, sex, diagnosis, stage, performance status, doses of carboplatin and etoposide, and concomitant treatment with melatonin or placebo, the haematological parameters – depth and duration of toxicity for haemoglobin, platelets and neutrophils (ANC) – were not significantly different between cycles with/without melatonin. The mean ANC nadir and the mean number of days with ANC < 0.5 × 109 l−1 were 0.5 × 109 l−1 and 2.5 days, respectively, with/without melatonin. We concluded that, in patients with lung cancer, melatonin given orally at a dose of 40 mg per day for 21 days in the evening, does not protect against the myelotoxic effect of carboplatin and etoposide. © 1999 Cancer Research Campaign

Keywords: myelotoxicity, chemotherapy, hormones, melatonin

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Footnotes

Presented in part at the annual meeting of the American Society of Clinical Oncology 1997

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aldeghi R., Lissoni P., Barni S., Ardizzoia A., Tancini G., Piperno A., Pozzi M., Ricci G., Conti A., Maestroni G. J. Low-dose interleukin-2 subcutaneous immunotherapy in association with the pineal hormone melatonin as a first-line therapy in locally advanced or metastatic hepatocellular carcinoma. Eur J Cancer. 1994;30A(2):167–170. doi: 10.1016/0959-8049(94)90080-9. [DOI] [PubMed] [Google Scholar]
  2. Aldhous M., Franey C., Wright J., Arendt J. Plasma concentrations of melatonin in man following oral absorption of different preparations. Br J Clin Pharmacol. 1985 Apr;19(4):517–521. doi: 10.1111/j.1365-2125.1985.tb02679.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arendt J. Melatonin. BMJ. 1996 May 18;312(7041):1242–1243. doi: 10.1136/bmj.312.7041.1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brzezinski A. Melatonin in humans. N Engl J Med. 1997 Jan 16;336(3):186–195. doi: 10.1056/NEJM199701163360306. [DOI] [PubMed] [Google Scholar]
  5. Canellos G. P. High-dose therapy: here to stay or just visiting? J Clin Oncol. 1994 Jan;12(1):5–6. doi: 10.1200/JCO.1994.12.1.5. [DOI] [PubMed] [Google Scholar]
  6. Capizzi R. L., Scheffler B. J., Schein P. S. Amifostine-mediated protection of normal bone marrow from cytotoxic chemotherapy. Cancer. 1993 Dec 1;72(11 Suppl):3495–3501. doi: 10.1002/1097-0142(19931201)72:11+<3495::aid-cncr2820721617>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  7. Crinò L., Clerici M., Figoli F., Carlini P., Ceci G., Cortesi E., Carpi A., Santini A., Di Costanzo F., Boni C. Chemotherapy of advanced non-small-cell lung cancer: a comparison of three active regimens. A randomized trial of the Italian Oncology Group for Clinical Research (G.O.I.R.C.). Ann Oncol. 1995 Apr;6(4):347–353. doi: 10.1093/oxfordjournals.annonc.a059183. [DOI] [PubMed] [Google Scholar]
  8. Genevay M. C., Mormont C., Thomas F., Berthier R. The synthetic tetrapeptide AcSDKP protects cells that reconstitute long-term bone marrow stromal cultures from the effects of mafosfamide (Asta Z 7654). Exp Hematol. 1996 Jan;24(1):77–81. [PubMed] [Google Scholar]
  9. Gurney H., Dodwell D., Thatcher N., Tattersall M. H. Escalating drug delivery in cancer chemotherapy: a review of concepts and practice--Part 1. Ann Oncol. 1993 Jan;4(1):23–34. doi: 10.1093/oxfordjournals.annonc.a058348. [DOI] [PubMed] [Google Scholar]
  10. Ihde D. C. Chemotherapy of lung cancer. N Engl J Med. 1992 Nov 12;327(20):1434–1441. doi: 10.1056/NEJM199211123272006. [DOI] [PubMed] [Google Scholar]
  11. Jelínek J., Fairbairn L. J., Dexter T. M., Rafferty J. A., Stocking C., Ostertag W., Margison G. P. Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase. Blood. 1996 Mar 1;87(5):1957–1961. [PubMed] [Google Scholar]
  12. Lissoni P., Barni S., Crispino S., Tancini G., Fraschini F. Endocrine and immune effects of melatonin therapy in metastatic cancer patients. Eur J Cancer Clin Oncol. 1989 May;25(5):789–795. doi: 10.1016/0277-5379(89)90122-3. [DOI] [PubMed] [Google Scholar]
  13. Lissoni P., Barni S., Tancini G., Ardizzoia A., Ricci G., Aldeghi R., Brivio F., Tisi E., Rovelli F., Rescaldani R. A randomised study with subcutaneous low-dose interleukin 2 alone vs interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma. Br J Cancer. 1994 Jan;69(1):196–199. doi: 10.1038/bjc.1994.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lissoni P., Tisi E., Barni S., Ardizzoia A., Rovelli F., Rescaldani R., Ballabio D., Benenti C., Angeli M., Tancini G. Biological and clinical results of a neuroimmunotherapy with interleukin-2 and the pineal hormone melatonin as a first line treatment in advanced non-small cell lung cancer. Br J Cancer. 1992 Jul;66(1):155–158. doi: 10.1038/bjc.1992.234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Maestroni G. J., Conti A., Lissoni P. Colony-stimulating activity and hematopoietic rescue from cancer chemotherapy compounds are induced by melatonin via endogenous interleukin 4. Cancer Res. 1994 Sep 1;54(17):4740–4743. [PubMed] [Google Scholar]
  16. Maestroni G. J., Covacci V., Conti A. Hematopoietic rescue via T-cell-dependent, endogenous granulocyte-macrophage colony-stimulating factor induced by the pineal neurohormone melatonin in tumor-bearing mice. Cancer Res. 1994 May 1;54(9):2429–2432. [PubMed] [Google Scholar]
  17. Maestroni G. J., Hertens E., Galli P., Conti A., Pedrinis E. Melatonin-induced T-helper cell hematopoietic cytokines resembling both interleukin-4 and dynorphin. J Pineal Res. 1996 Oct;21(3):131–139. doi: 10.1111/j.1600-079x.1996.tb00280.x. [DOI] [PubMed] [Google Scholar]
  18. Neri B., Fiorelli C., Moroni F., Nicita G., Paoletti M. C., Ponchietti R., Raugei A., Santoni G., Trippitelli A., Grechi G. Modulation of human lymphoblastoid interferon activity by melatonin in metastatic renal cell carcinoma. A phase II study. Cancer. 1994 Jun 15;73(12):3015–3019. doi: 10.1002/1097-0142(19940615)73:12<3015::aid-cncr2820731220>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  19. Waldhauser F., Waldhauser M., Lieberman H. R., Deng M. H., Lynch H. J., Wurtman R. J. Bioavailability of oral melatonin in humans. Neuroendocrinology. 1984 Oct;39(4):307–313. doi: 10.1159/000123997. [DOI] [PubMed] [Google Scholar]

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