Melatonin can improve the survival of lung cancer in the late stage after surgical resection

reference

SEILY D, Legacy M, Auer RC, et al. Adjuvantes melatonin for the prevention of recurrences and mortality after lung Cancer resection (amplcare): a randomized placebo -controlled clinical study. eclinical medicine . 2021; 33: 100763.

Study goal

Assessment of the effects of melatonin on the recurrence and the mortality of lung cancer after surgical resection within a period of 5 years as well as explanation of the effects on quality of life, symptoms and immune function

draft

Multicentric, 2-armed, placebo-controlled, double-blind, randomized, controlled phase 3 study with participants who received 20 mg melatonin compared to placebo

participant

adults with primary non-small cell lung cancer (NSCLC), which were considered for a complete surgical resection, took part in the study. The researchers excluded patients who already had melatonin, had incomplete resection or were pregnant or were still. They recruited and randomized a total of 709 patients (356 melatonin group, 353 placebo group) from 8 centers. The average age was 67.2 ± 8.5 years. In the Melatonin group, 46.6 % of the participants were male and 40.7 % of the participants in the placebo group were male. Preoperative chemotherapy or radiation compared to 3.9 % in the placebo group received preoperative chemotherapy from the participants. In the Melatonin group, 13.2 % were current smokers and 14.6 % of the placebo group were current smokers. In the Melatonin group there were 78.6 % of former smokers and 73.9 % of the placebo group were former smokers.

study parameters evaluated

The 2 groups of lung cancer patients, those who took melatonin, and those who did not take a melatonin were compared using numerous statistical tests to determine whether melatonin delayed the progression of the cancer or extended the patient's survival. The primary endpoint was the disease -free survival (DFS) after 2 years. DFS up to 5 years after the operation was also compared with Kaplan-Meier curves.

primary result measurements

The primary endpoint was the 2-year DFS, whereby the incidence of recurrences or mortality was assessed 2 years after the surgical resection. The study used the clinical examination by the thoracic surgeon and the radiological detection of the disease as a marker for recurring. In most centers, doctors carried out annual computer tomography (CT) scans and clinical examinations. However, they also used a number of other imaging studies for evaluation, depending on the preferences of the doctor.

important knowledge

Two -year DFS in patients who took melatonin had an adjusted relative risk of 1.01 (95 % CI 0.83–1.22, p = 0.94) compared to placebo. The Per Protocol analysis showed an adjusted relative risk of 1.12 (95 % CI 0.96–1.32, p = 0.14).

None of the arms reached a 5-year median DFS. The melatonin group showed a Hazard ratio of 0.97 (95 % KI 0.86–1.09, p = 0.84) for 5-year DFS compared to the placebo group. The melatonin group showed a hazard ratio of 0.97 (95 % KI 0.85–1.11, p = 0.66) in the group in early stage (I and II) and a hazard reduction of 25 % (HR 0.75, 95 % KI 0.61–0.92, p = 0.005) in the group in late stage (III and IV). The early stages did not reach 5-year median DFS. In the late stage group there was no difference in the median DFS (melatonin arm: 18.0 months [95% CI 9.426.6]; placebo arm: 18.0 months [95% CI 2.223.8]). The study showed no benefits in the use of melatonin in chemotherapy and irradiation of radiation, quality of life, fatigue, sleep, depression, fear and pain with a dose of 20 mg in this population.

practice implications

melatonin has long been a popular substance that is used in the world of naturopathic and allopathic medicine because of its remarkable advantages in the treatment of insomnia and circadian regulation.

The relevance of this study goes beyond improving sleep, since it indicates the potential for improving the survival time, especially for patients with lung cancer in late stage.

lung cancer is still the type of cancer with the second highest incidence in both sexes, behind prostate cancer in men and breast cancer in women; It also has the highest mortality rate among all types of cancer for both genders around the world. ^{2 In addition, there was a trend towards new cancer diagnoses for non -smokers, which tend to be women with adenocarcinoma who were found in a later and more advanced stage. to look for less effect on the quality of life.}

Studies that examine the benefits of melatonin at NSCLC patients who undergo chemotherapy show favorable results, in particular when improving the effectiveness of chemotherapy and reducing toxicity. ^{4 There were fewer studies that deal with the results after surgical resection, which makes this current study significant.}

melatonin continues to be investigated, with newer articles pointing out its numerous advantages. ^{5 There are many therapeutic potential for this substance in lung cancer, but also with a variety of other types of tumor. Gurunathan et al. In her overview, explicitly mention that "the combination of melatonin with conventional drugs improves the drug sensitivity of cancer, including solid and fluid tumors."}

Studies that examine the benefits of melatonin in NSCLC patients who undergo chemotherapy show favorable results, especially when improving the effectiveness of chemotherapy and reducing toxicity.

Further studies should ideally also deal with the combination of melatonin with some of the more newer oral targeted medication such as Erlotinib and Osimmerinib, which clinicists use as first -line treatment for diseases in late stage.

We as a clinician are constantly looking for methods to improve the quality of life of our patients and to extend survival. Although the number of patients in the late stage in this study was low, the effects are very positive and will probably help to initiate similar studies.

This study will probably encourage more doctors to supplement their NSCLC patients in stage III and IV with 20 mg melatonin, especially after a surgical resection. In view of the abundance of data for benefit even during chemotherapy, however, there is a greater probability that the majority of patients would benefit from the addition of melatonin in the late stage.