Lissoni · European journal of cancer (Oxford, England : 1990) 1999 · randomized controlled trial · n=250

Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status.

Cited 253 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial

PubMed 10674014 · doi:10.1016/s0959-8049(99)00159-8 · record verified 2026-08-30

What was done

A randomized controlled trial enrolled 250 patients with metastatic solid tumors (lung cancer, n = 104; breast cancer, n = 77; gastrointestinal neoplasms, n = 42; head and neck cancers, n = 27) and poor clinical status. Participants were randomized to receive chemotherapy alone (n = 126) or chemotherapy plus oral melatonin at 20 mg/day daily (n = 124). Chemotherapy regimens varied by tumor type (cisplatin plus etoposide or gemcitabine for lung; doxorubicin, mitoxantrone, or paclitaxel for breast; 5-FU plus folinic acid for gastrointestinal; 5-FU plus cisplatin for head and neck).

What was found

Compared with chemotherapy alone, chemotherapy plus melatonin significantly increased: - Objective tumor response rate: 42/124 (33.9%) vs 19/126 (15.1%), P < 0.001. - 1-year survival rate: 63/124 (50.8%) vs 29/126 (23.0%), P < 0.001. Concomitant melatonin also significantly reduced the reported frequency of thrombocytopenia, neurotoxicity, cardiotoxicity, stomatitis, and asthenia (specific incidence numbers per toxicity were not reported in the abstract).

Why it matters

This study suggests that high-dose daily melatonin may serve as an adjuvant that reduces multi-organ chemotherapy toxicities and improves tumor response and survival in advanced cancer patients with poor performance status.

Limits

The cohort pooled four distinct cancer types receiving multiple disparate chemotherapy regimens, confounding tumor-specific conclusions. The abstract does not mention placebo control or blinding procedures (suggesting an open-label design prone to assessment bias), nor does it report exact numerical rates for individual toxicities, median survival times, or formal quality-of-life scores.

Cited by