A Phase I Study of High-Dose Calcitriol in Combination with Temozolomide for Patients with Metastatic Melanoma
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 ad...
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| Format: | Article |
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MDPI AG
2014-10-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | http://www.mdpi.com/2075-4426/4/4/448 |
| _version_ | 1797760912359161856 |
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| author | Erin Pettijohn Brenda Martone Alfred Rademaker Timothy Kuzel |
| author_facet | Erin Pettijohn Brenda Martone Alfred Rademaker Timothy Kuzel |
| author_sort | Erin Pettijohn |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T19:05:22Z |
| format | Article |
| id | doaj.art-8b59f286558d4998a7f77ba5353c6e55 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-12T19:05:22Z |
| publishDate | 2014-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-8b59f286558d4998a7f77ba5353c6e552023-08-02T06:19:03ZengMDPI AGJournal of Personalized Medicine2075-44262014-10-014444845810.3390/jpm4040448jpm4040448A Phase I Study of High-Dose Calcitriol in Combination with Temozolomide for Patients with Metastatic MelanomaErin Pettijohn0Brenda Martone1Alfred Rademaker2Timothy Kuzel3Division of Hematology/Oncology, Northwestern University, 676 N. St Clair, Suite 850, Chicago, IL 60611, USADivision of Hematology/Oncology, Northwestern University, 676 N. St Clair, Suite 850, Chicago, IL 60611, USADivision of Biostatistics, Department of Preventative Health, Feinberg School of Medicine, Northwestern University, 680 N. Lakeshore Drive, Suite 1400, Chicago, IL 60611, USADivision of Hematology/Oncology, Northwestern University, 676 N. St Clair, Suite 850, Chicago, IL 60611, USABackground: 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.http://www.mdpi.com/2075-4426/4/4/448metastatic melanomavitamin D receptor polymorphismstemozolomidecalcitriolTaq1Fok1 |
| spellingShingle | Erin Pettijohn Brenda Martone Alfred Rademaker Timothy Kuzel A Phase I Study of High-Dose Calcitriol in Combination with Temozolomide for Patients with Metastatic Melanoma Journal of Personalized Medicine metastatic melanoma vitamin D receptor polymorphisms temozolomide calcitriol Taq1 Fok1 |
| title | A Phase I Study of High-Dose Calcitriol in Combination with Temozolomide for Patients with Metastatic Melanoma |
| title_full | A Phase I Study of High-Dose Calcitriol in Combination with Temozolomide for Patients with Metastatic Melanoma |
| title_fullStr | A Phase I Study of High-Dose Calcitriol in Combination with Temozolomide for Patients with Metastatic Melanoma |
| title_full_unstemmed | A Phase I Study of High-Dose Calcitriol in Combination with Temozolomide for Patients with Metastatic Melanoma |
| title_short | A Phase I Study of High-Dose Calcitriol in Combination with Temozolomide for Patients with Metastatic Melanoma |
| title_sort | phase i study of high dose calcitriol in combination with temozolomide for patients with metastatic melanoma |
| topic | metastatic melanoma vitamin D receptor polymorphisms temozolomide calcitriol Taq1 Fok1 |
| url | http://www.mdpi.com/2075-4426/4/4/448 |
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