A Phase I study of high-dose calcitriol in combination with temozolomide for patients with metastatic melanoma

Erin Pettijohn, Brenda Martone, Alfred Rademaker, Timothy Michael Kuzel*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Temozolomide is efficacious as an oral alternative for patients with metastatic melanoma (MM). Calcitriol has anti-proliferative properties and vitamin D receptor (VDR) polymorphisms are associated with alterations in melanoma susceptibility and progression. Methods: Tem 150 mg/m2 was administered on days 2–8 and 16–22 every 28 days. Calcitriol was given on days 1 and 15 every 28 days. VDR gene analysis was completed using PCR-RFLP based assays. Tolerability was the primary objective with secondary objectives of time to progression (TTP) and overall survival (OS). Results: Twenty pts with MM were registered. Cytopenias and thrombosis were the most common grade 3 or 4 toxicities. Median TTP was 1.8 mo. Pts with high-risk VDR genotype tt+/−ff (n = 6) had an OS of 3.8 mo from time of enrollment, compared to 7.4 mo for those with non-tt/ff genotypes (n = 11), although not statistically significant (HR = 1.20, 95% CI 0.41–3.53, p = 0.74). Conclusions: The extended dosing of Tem with calcitriol is a well-tolerated regimen. The trend toward improved OS in non-tt/ff VDR genotypes is consistent with prior studies associating the tt/ff genotype with biologic aggressiveness.

Original languageEnglish (US)
Pages (from-to)448-458
Number of pages11
JournalJournal of Personalized Medicine
Volume4
Issue number4
DOIs
StatePublished - Jan 1 2014

Keywords

  • Calcitriol
  • Fok1
  • Metastatic melanoma
  • Taq1
  • Temozolomide
  • Vitamin D receptor polymorphisms

ASJC Scopus subject areas

  • Medicine (miscellaneous)

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