RESUMEN
BACKGROUND: Transplant related toxicity is a major therapeutic challenge. We have previously reported that the toxicity of chemotherapy is largely not directly because of the drugs themselves; rather it is mainly due to DNA damage, apoptosis and hyper-inflammation triggered by cell-free chromatin particles that are released because of drug-induced host cell death. Cell-free chromatin particles can be inactivated by free-radicals which are generated when the nutraceuticals resveratrol and copper are administered orally. We investigated if a combination of resveratrol and copper would reduce transplant related toxicities in an exploratory, prospective dose-escalation study. PATIENTS AND METHODS: Twenty-five patients with multiple myeloma were enrolled between March 2017 to August 2019. Patients were divided into 3 groups: control (Group 1, N = 5) received vehicle alone; group 2 (N = 15) received resveratrol-copper at dose level I (resveratrol = 5.6 mg and copper = 560 ng); group 3 (N = 5) received resveratrol-copper at dose level II (resveratrol = 50 mg and copper = 5 µg). The dose was given twice daily with the first dose administered 48 hours before administering melphalan and continued until day +21 post-transplant. Common Terminology Criteria for Adverse Events version 4.02 was used to assess toxicities which included oral mucositis, nausea, vomiting and diarrhea. Measurement of inflammatory cytokines was done by ELISA. RESULTS: All patients (100%) in the control group developed grade 3/4 oral mucositis compared to 8/20 (40%) in both resveratrol-copper group 2 plus group 3 combined (P = 0.039). Reduction in inflammatory cytokines: salivary TNF - α (p = 0.012) and IL-1ß (p = 0.009) in dose level I but not in dose level II was observed. CONCLUSIONS: A combination of resveratrol-copper reduced transplant related toxicities in patients with multiple myeloma receiving high dose melphalan. We conclude that relatively inexpensive nutraceuticals may be useful as adjuncts to chemotherapy to reduce its toxicity. REGISTRATION: The trial was registered under Clinical Trial Registry of India (no.CTRI/2018/02/011905).
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MelfalánRESUMEN
Low- and middle-income countries (LMICs) have limited financial resources and proportionately smaller portions allocated for health budget. With competing health priorities, treatment of the diagnosed cases and establishment of treatment facilities are the main concerns in LMICs. Infectious diseases, reducing infant, child and maternal mortality may seem crucial as compared to early cancer detection. LMICs that are committed to providing comprehensive cancer care, will need to judiciously choose the screening tool depending on specifics of how the tool is expected to perform in the population and the cost-effectiveness with respect to the number of lives expected to be saved. Increasing awareness about breast health in general and common cancers and non communicable diseases (NCDs), in particular, may lead to symptomatic women approaching the healthcare facilities at an earlier stage. When the limited available resources are mobilized towards cancer screening, increasing awareness would lead to greater acceptability of the programme. The reach of the programme to achieve good population coverage, the establishment of the diagnostic referral linkages and the availability and accessibility of treatment facilities, will all decide the outcome of the screening programme.