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

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 × 10 9 l −1 were 0.5 × 10 9 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

Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

“…(19,20,21,22,23,11,24,25,26,27,28,29,30,31,32, 33) Three independent randomized trials, including this trial, have been run. (34,35) It is noteworthy that all of the trials from Lissoni and colleagues have had positive outcomes and, as of yet, there have been no confirmatory publications from outside of his group.…”

“…(19,20,21,22,23,11,24,25,26,27,28,29,30,31,32,33) Three independent randomized trials, including this trial, have been run. (34,35) It is noteworthy that all of the trials from Lissoni and colleagues have had positive outcomes and, as of yet, there have been no confirmatory publications from outside of his group.The difference could reflect a difference in the biological properties of the melatonin being used. Melatonin has very poor bioavailability, with approximately 15% absorption.…”

Nutrition During and After Cancer Treatment: A Guide for Informed Choices by Cancer Survivors

“…[19][20][21] Even endogenous antioxidants, such as melatonin, might work to enhance chemotherapy, 22 but such findings have not consistently been reproduced. 23 Unfortunately, this is one of the many critical questions without a good answer at this time. Therefore, it would be prudent to advise patients undergoing chemotherapy or radiotherapy not to exceed the upper intake limits of the Dietary Reference Intakes for vitamin supplements and to avoid other nutritional supplements that contain antioxidant compounds.…”

Efficacy and Interaction of Antioxidant Supplements as Adjuvant Therapy in Cancer Treatment

“…66 The study of Cerea et al 67 and many other studies [63][64][65][66]68,69 reported positive results regarding toxicity reduction and clinical response. However, Ghielmini et al 61 performed a double-blind and placebo RCT for NSCLC patients whose chemotherapy regimen included cisplatin and etoposide. They reported that there was no significant difference in regard to hematological toxicity in their trial.…”

“…Myeloprotective and immunoenhancing effects of melatonin have been demonstrated in in vitro and in vivo experimental models. 60,61 Melatonin, a potent antioxidant, plays various roles in regulating circadian rhythms, sleep, tumor growth, and ageing. For many years, it has been known that it plays an important anticancer role.…”