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Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase 1 results from the multicenter EVOLUTION study. Leukemia 2010 Jul;24(7):1350-6 PMID: 20508619 PMCID: PMC2957585

Pubmed ID

20508619

Abstract

This phase 1 study (Clinicaltrials.gov: NCT00507442) was conducted to determine the maximum tolerated dose (MTD) of cyclophosphamide in combination with bortezomib, dexamethasone and lenalidomide (VDCR) and to assess the safety and efficacy of this combination in untreated multiple myeloma patients. Cohorts of three to six patients received a cyclophosphamide dosage of 100, 200, 300, 400 or 500 mg/m(2) (on days 1 and 8) plus bortezomib 1.3 mg/m(2) (on days 1, 4, 8 and 11), dexamethasone 40 mg (on days 1, 8 and 15) and lenalidomide 15 mg (on days 1-14), for eight 21-day induction cycles, followed by four 42-day maintenance cycles (bortezomib 1.3 mg/m(2), on days 1, 8, 15 and 22). The MTD was the cyclophosphamide dose below which more than one of six patients experienced a dose-limiting toxicity (DLT). Twenty-five patients were treated. Two DLTs were seen, of grade 4 febrile neutropenia (cyclophosphamide 400 mg/m(2)) and grade 4 herpes zoster despite anti-viral prophylaxis (cyclophosphamide 500 mg/m(2)). No cumulative hematological toxicity or thromboembolic episodes were reported. The overall response rate was 96%, including 20% stringent complete response (CR), 40% CR/near-complete response and 68% >or=very good partial response. VDCR is well tolerated and highly active in this population. No MTD was reached; the recommended phase 2 cyclophosphamide dose in VDCR is 500 mg/m(2), which was the highest dose tested.

Author List

Kumar SK, Flinn I, Noga SJ, Hari P, Rifkin R, Callander N, Bhandari M, Wolf JL, Gasparetto C, Krishnan A, Grosman D, Glass J, Sahovic EA, Shi H, Webb IJ, Richardson PG, Rajkumar SV

Author

Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-77954660886   65 Citations

MESH terms used to index this publication - Major topics in bold

Aged
Antineoplastic Combined Chemotherapy Protocols
Boronic Acids
Bortezomib
Cohort Studies
Cyclophosphamide
Dexamethasone
Female
Follow-Up Studies
Humans
Male
Maximum Tolerated Dose
Middle Aged
Multiple Myeloma
Neoplasm Recurrence, Local
Pyrazines
Remission Induction
Survival Rate
Thalidomide
Treatment Outcome
jenkins-FCD Prod-296 4db9d02597e0a2e889e230f853b641c12f1c3ee3