What are the current findings on using melatonin as an adjuvant (additional) therapy for cancer?

Melatonin as an Adjuvant Therapy for Cancer: Current Evidence

Based on current clinical guidelines and research, melatonin is not recommended as an adjuvant therapy for cancer due to insufficient evidence of clinical benefit for mortality, morbidity, or quality of life outcomes. 1

Evidence from Clinical Guidelines

Efficacy for Cancer-Related Symptoms

The most recent evidence from high-quality clinical guidelines shows:

• A randomized crossover trial (N=72) of patients with advanced cancer found no significant improvement in fatigue with melatonin (20 mg daily) compared to placebo 1
• The European Society for Medical Oncology (ESMO) explicitly states that "the use of melatonin is not recommended for the control of cancer-related fatigue" with a level II, D evidence rating 1
• For anxiety and depression in cancer patients, trials of melatonin have shown inconsistent results:
  • One small RCT (N=54) showed reduction in depression in women with breast cancer during the perioperative period 1
  • However, other trials showed no impact on anxiety or depression in colorectal cancer patients receiving chemotherapy or lung cancer patients post-resection 1

Dosing and Administration

When melatonin has been studied in cancer patients:

• Doses have ranged from 3-20 mg daily
• Most common administration is at bedtime
• Duration of treatment has varied significantly across studies 1, 2

Preclinical vs. Clinical Evidence

There is a significant disconnect between preclinical and clinical evidence:

• Preclinical studies suggest multiple anti-cancer mechanisms including:

  • Inhibition of cancer initiation, progression, and metastasis 3
  • Apoptosis induction and cell proliferation inhibition 4
  • Antioxidant and immunomodulatory effects 5

• However, clinical evidence from randomized controlled trials has failed to demonstrate consistent benefits for:

  • Cancer-related fatigue 1
  • Anxiety and depression in most cancer populations 1
  • Overall survival or disease progression 6

Potential as Chemotherapy Adjuvant

Some research suggests melatonin might:

• Reduce side effects associated with chemotherapy and radiotherapy 4, 7
• Potentially decrease drug resistance in cancer therapy 4
• Enhance the therapeutic effects of conventional anticancer therapies 7

However, these findings have not been consistently demonstrated in large, high-quality clinical trials that would warrant inclusion in clinical guidelines.

Clinical Application Algorithm

For clinicians considering melatonin in cancer care:

1. First-line approach: Do not recommend melatonin specifically as an anti-cancer agent or for cancer-related fatigue due to insufficient evidence 1

2. For sleep disturbances in cancer patients:

   • Consider evidence-based cognitive behavioral therapy for insomnia (CBT-I) as first-line 1
   • Short-term pharmacological solutions may be necessary until CBT takes effect 1
   • Melatonin is not specifically recommended over other sleep aids in cancer patients 1

3. For patients insistent on using melatonin:

   • Inform about the lack of strong clinical evidence for cancer-specific benefits
   • Monitor for potential interactions with chemotherapy agents
   • Typical doses used in studies range from 3-20 mg daily 1, 2
   • Document discussion of limitations in evidence

Conclusion

Despite promising preclinical research and some positive small studies, current clinical guidelines do not support the use of melatonin as an adjuvant therapy for cancer treatment or symptom management. More rigorous clinical trials are needed before melatonin can be recommended as part of standard cancer care.