medwireNews: Vitamin D deficiency is common in patients undergoing chemotherapy for Hodgkin’s lymphoma (HL) and may be an independent predictor of survival, German researchers believe after analysing data from three clinical trials.
“On the basis of our study results and the limited toxicity of vitamin D replacement therapy, we would advocate for vitamin D deficiency screening and replacement to be incorporated into future randomized clinical trials to properly clarify the role of vitamin D replacement in HL”, say Sven Borchmann, from the University Hospital of Cologne, and co-workers.
The authors also advise in the Journal of Clinical Oncology: “In the absence of such high-level, prospective evidence, treating institutions may wish to consider an individual approach to screening for vitamin D deficiency and potential replacement in patients with HL.”
The team collated data from 351 participants of the German Hodgkin Study Group HD7, HD8 and HD9 trials and found 50% of the patients beginning chemotherapy were deficient for vitamin D according to a “conservative” threshold of less than 30 nmol/L, which was based on the level required for clinical deficiency syndromes rather than dietary insufficiency.
Analysis showed that pretreatment vitamin D deficiency was significantly more common in patients who relapsed or had treatment-refractory disease than patients who were free from relapse, at 68% versus 41%.The median baseline vitamin D levels were 21.4 and 35.5 nmol/L, respectively.
Patients with baseline vitamin D deficiency also had significantly poorer 5- and 10-year progression-free survival (PFS) and overall survival (OS) than those without vitamin D deficiency, say the researchers who note that this relationship was “consistent across trials and treatment groups.”
Specifically, after a median of 13 years of follow-up, 10-year PFS was achieved by 64.2% of deficient patients versus 81.8% of those without deficiency, giving a hazard ratio (HR) for death or progression of 2.13. The corresponding values for OS after a median of 16 years were 76.1% versus 87.2% and a HR for death of 1.82.
“The difference in OS primarily resulted from a higher proportion of HL-related deaths in patients with baseline deficiency of vitamin D”, the authors observe.
The team used cell line models to further explore the relationship between vitamin D and chemotherapy, finding that a physiological dose of the active form of vitamin D calcitriol was associated with increased cytotoxicity of doxorubicin and etoposide, but not vinorelbine or cisplatin.
And this effect was confirmed in a mouse xenograft study showing that combining vitamin D supplementation with doxorubicin was “markedly more effective in controlling tumor growth compared with placebo-treated controls and monotherapy with either vitamin D supplementation or doxorubicin.”
Sven Borchmann and co-authors say their “data suggest that vitamin D supplementation may act synergistically with commonly used chemotherapy in HL”, but admit that “[t]he best schedule for vitamin D replacement in deficient patients remains unclear, because aggressive replacement strategies might be more effective at correcting levels during chemotherapy.”
Borchmann S, Cirillo M, Goergen H, et al. Pretreatment vitamin D deficiency is associated with impaired progression-free and overall survival in Hodgkin lymphoma. J Clin Oncol; Advance online publication 17 October 2019. DOI: 10.1200/JCO.19.00985
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