Abstract | PURPOSE: PATIENTS AND METHODS: RESULTS: RICOVER-60 patients with VDD (≤ 8 ng/mL) and vitamin D levels more than 8 ng/mL treated with rituximab had 3-year event-free survival (EFS) of 59% and 79% and 3-year overall survival (OS) of 70% and 82%, respectively. These differences were significant in a multivariable analysis adjusting for International Prognostic Index risk factors with a hazard ratio (HR) of 2.1 (P = .008) for EFS and 1.9 (P = .040) for OS. EFS was not significantly different in patients with vitamin D levels ≤ 8 or more than 8 ng/mL (HR, 1.2; P = .388) treated without rituximab. This was confirmed in an independent validation set of 63 RICOVER-noRTh patients. RMCC increased significantly (P < .001) in seven of seven individuals with VDD after substitution and normalization of their vitamin D levels. CONCLUSION: VDD is a risk factor for elderly patients with DLBCL treated with R-CHOP. That VDD impairs RMCC and substitution improves RMCC strongly suggests that vitamin D substitution enhances rituximab efficacy, which must be confirmed in appropriately designed prospective trials addressing VDD and substitution not only in DLBCL, but also in malignancies treated with other antibodies, of which the major mechanism of action is antibody-dependent cellular cytotoxicity (eg, trastuzumab in breast cancer and cetuximab in colorectal cancer).
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Authors | Jörg Thomas Bittenbring, Frank Neumann, Bettina Altmann, Marina Achenbach, Jörg Reichrath, Marita Ziepert, Jürgen Geisel, Evi Regitz, Gerhard Held, Michael Pfreundschuh |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 32
Issue 29
Pg. 3242-8
(Oct 10 2014)
ISSN: 1527-7755 [Electronic] United States |
PMID | 25135997
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 by American Society of Clinical Oncology. |
Chemical References |
- Antibodies, Monoclonal, Murine-Derived
- Antineoplastic Agents
- Rituximab
- Vincristine
- Doxorubicin
- Cyclophosphamide
- Calcifediol
- Prednisone
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Topics |
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal, Murine-Derived
(administration & dosage, therapeutic use)
- Antineoplastic Agents
(administration & dosage, therapeutic use)
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage)
- Calcifediol
(blood)
- Cyclophosphamide
(administration & dosage)
- Doxorubicin
(administration & dosage)
- Female
- Humans
- Lymphoma, Large B-Cell, Diffuse
(drug therapy)
- Male
- Middle Aged
- Prednisone
(administration & dosage)
- Risk Factors
- Rituximab
- Treatment Outcome
- Vincristine
(administration & dosage)
- Vitamin D Deficiency
(complications)
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