Phase I/II trial of vorinostat with rituximab, cyclophosphamide, etoposide and prednisone as palliative treatment for elderly patients with relapsed or refractory diffuse large B-cell lymphoma not eligible for autologous stem cell transplantation Journal Article


Authors: Straus, D. J.; Hamlin, P. A.; Matasar, M. J.; Lia Palomba, M.; Drullinsky, P. R.; Zelenetz, A. D.; Gerecitano, J. F.; Noy, A.; Hamilton, A. M.; Elstrom, R.; Wegner, B.; Wortman, K.; Cella, D.
Article Title: Phase I/II trial of vorinostat with rituximab, cyclophosphamide, etoposide and prednisone as palliative treatment for elderly patients with relapsed or refractory diffuse large B-cell lymphoma not eligible for autologous stem cell transplantation
Abstract: Summary: The standard treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in frail elderly patients has not been established. A variation was made on rituximab (R), cyclophosphamide (C), etoposide (E), procarbazine and prednisone (P), substituting vorinostat (V) for procarbazine. Patients ≥aged 60 years with relapsed/refractory DLBCL, not candidates for autologous stem cell transplantation, were treated R-CVEP [R 375 mg/m2 intravenously (IV), day 1; C 600 mg/m2 IV days 1, 8: E 70 mg/m2 IV day 1, 140 mg/m2 days 2, 3 orally (PO); V (300 vs. 400 mg) PO and P 60 mg/m2 PO days 1-10] every 28 d for six cycles. Quality of life (QoL) was assessed in addition to response. Thirty patients (median age 76 years, 69-88) were enrolled (one died before treatment). Maximum tolerated dose (MTD) for V was 300 mg. For 23 patients at MTD (six phase I + 17 phase II), two were discontinued for toxicity, one withdrew consent, eight achieved complete response (35%), five achieved partial response (22%) and seven progressed (25%). Median overall survival was 17·5 months. Median progression-free survival was 9·2 months. Nine patients are alive. QoL declined during treatment but improved above baseline for patients who completed treatment. In conclusion, R-CVEP was tolerated at MTD and produced durable responses with improved QoL.
Keywords: clinical article; treatment response; aged; overall survival; prednisone; drug tolerability; fatigue; neutropenia; cancer growth; diarrhea; drug dose comparison; drug efficacy; drug withdrawal; hypophosphatemia; patient selection; unspecified side effect; rituximab; cancer palliative therapy; progression free survival; quality of life; infection; multiple cycle treatment; phase 2 clinical trial; anemia; etoposide; bleeding; blood toxicity; leukopenia; mucosa inflammation; thrombocytopenia; dehydration; cohort analysis; cyclophosphamide; autologous stem cell transplantation; hypercalcemia; asthenia; dyspnea; febrile neutropenia; hyperglycemia; lymphocytopenia; hypoxia; hyperkalemia; hypokalemia; hyponatremia; hypotension; malaise; survival time; cancer regression; thrombosis; vorinostat; peripheral edema; open study; large cell lymphoma; maximum tolerated dose; phase 1 clinical trial; embolism; heart arrhythmia; lethargy; treatment contraindication; brain ischemia; elderly care; frail elderly; elderly; diffuse large b-cell lymphoma; filgrastim; combination; thrombus; relapsed/refractory; pegfilgrastim; very elderly; human; male; female; article
Journal Title: British Journal of Haematology
Volume: 168
Issue: 5
ISSN: 0007-1048
Publisher: John Wiley & Sons  
Date Published: 2015-03-01
Start Page: 663
End Page: 670
Language: English
DOI: 10.1111/bjh.13195
PROVIDER: scopus
PUBMED: 25316653
DOI/URL:
Notes: Export Date: 2 March 2015 -- Source: Scopus
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MSK Authors
  1. Ariela Noy
    208 Noy
  2. Maria Lia Palomba
    128 Palomba
  3. Andrew D Zelenetz
    556 Zelenetz
  4. Paul Hamlin
    174 Hamlin
  5. Matthew J Matasar
    122 Matasar
  6. David J Straus
    213 Straus
  7. Brett C Wegner
    7 Wegner