title: A phase I study of high-dose calcitriol in combination with temozolomide for patients with metastatic melanoma.
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.
authors.affiliation: Division of Hematology/Oncology, Northwestern University, 676 N. St Clair, Suite 850, Chicago, IL 60611, USA. erin-pettijohn@northwestern.edu.
authors.forename: Erin
authors.initials: E
authors.lastname: Pettijohn
authors.affiliation: Division of Hematology/Oncology, Northwestern University, 676 N. St Clair, Suite 850, Chicago, IL 60611, USA. bmartone@nmff.org.
authors.forename: Brenda
authors.initials: B
authors.lastname: Martone
authors.affiliation: Division of Biostatistics, Department of Preventative Health, Feinberg School of Medicine, Northwestern University, 680 N. Lakeshore Drive, Suite 1400, Chicago, IL 60611, USA. rademaker@northwestern.edu.
authors.forename: Alfred
authors.initials: A
authors.lastname: Rademaker
authors.affiliation: Division of Hematology/Oncology, Northwestern University, 676 N. St Clair, Suite 850, Chicago, IL 60611, USA. t-kuzel@northwestern.edu.
authors.forename: Timothy
authors.initials: T
authors.lastname: Kuzel