Phase I trial of weekly and twice-weekly bortezomib with rituximab, cyclophosphamide, and prednisone in relapsed or refractory non-hodgkin lymphoma Journal Article

Authors: Gerecitano, J.; Portlock, C.; Hamlin, P.; Moskowitz, C. H.; Noy, A.; Straus, D.; Schulman, P.; Dumitrescu, O.; Sarasohn, D.; Pappanicholaou, J.; Iasonos, A.; Zhang, Z.; Mo, Q.; Horanlli, E.; Rojas, C. N.; Zelenetz, A. D.; O'Connor, O. A.
Article Title: Phase I trial of weekly and twice-weekly bortezomib with rituximab, cyclophosphamide, and prednisone in relapsed or refractory non-hodgkin lymphoma
Abstract: Purpose: To determine the safety and efficacy of substituting weekly or twice-weekly bortezomib for vincristine in the R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen in patients with relapsed/refractory indolent and mantle cell lymphoma (MCL). Experimental Design: Of the 57 patients in this phase I trial, 55 participated in 1 of 2 dosing schedules that included rituximab (375 mg/m2) and cyclophosphamide (750 or 1,000 mg/m2) administered on day 1 of each 21-day cycle and prednisone (100 mg orally) days 2 to 6. In the once-weekly schedule, bortezomib was administered on days 2 and 8; on the twice-weekly schedule, bortezomib was given on days 2, 5, 9, and 12. Bortezomib and cyclophosphamide were alternately escalated. A separate cohort of 10 patients in the twice-weekly schedule received concurrent pegfilgrastim (PegG) on day 2. Results: Both schedules of R-CBorP (rituximab, cyclophosphamide, bortezomib, and prednisone) were well tolerated. Most toxicities across all dose levels and cycles were grade 1 or 2. The overall response rates for patients on the weekly (n= 13) and twice-weekly (n = 33) schedules were 46% [23% complete response/complete response unconfirmed (CR/CRu)] and 64% (36% CR/CRu), respectively. Concurrent PegG did not increase hematologic toxicities in this regimen. A randomized phase II study is under way to further compare toxicity and efficacy of the 2 dosing schedules. Conclusions: R-CBorP is a safe and effective regimen in patients with relapsed/refractory indolent and MCLs. Most toxicities were grade 1 or 2, and a promising response rate was seen in this phase I study. © 2011 AACR.
Keywords: adult; controlled study; aged; major clinical study; prednisone; constipation; drug tolerability; fatigue; neutropenia; diarrhea; drug efficacy; drug safety; drug withdrawal; hypophosphatemia; side effect; unspecified side effect; rituximab; edema; bortezomib; controlled clinical trial; drug eruption; infection; mantle cell lymphoma; multiple cycle treatment; sensory neuropathy; anemia; blood toxicity; leukopenia; nausea; thrombocytopenia; vomiting; dehydration; alkylating agent; cyclophosphamide; chill; coughing; dizziness; drug dose escalation; drug fever; dyspnea; febrile neutropenia; hyperglycemia; hypomagnesemia; lymphocytopenia; pruritus; hypoxia; allergic rhinitis; hyperkalemia; hypoalbuminemia; hypokalemia; hyponatremia; insomnia; nonhodgkin lymphoma; rigor; dosage schedule comparison; drug response; urinary frequency; xerostomia; hypoglycemia; cancer relapse; purine derivative; pancytopenia; anxiety; phase 1 clinical trial; platinum complex; anthracycline derivative; recombinant granulocyte colony stimulating factor; radioimmunotherapy; drug dose regimen; hypernatremia; hypocalcemia; autologous peripheral blood stem cell transplantation; feces incontinence; sweating; skin bruising
Journal Title: Clinical Cancer Research
Volume: 17
Issue: 8
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2011-04-15
Start Page: 2493
End Page: 2501
Language: English
DOI: 10.1158/1078-0432.ccr-10-1498
PROVIDER: scopus
PUBMED: 21346146
PMCID: PMC5639472
Notes: --- - "Export Date: 23 June 2011" - "CODEN: CCREF" - "Source: Scopus"
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MSK Authors
  1. Qianxing Mo
    37 Mo
  2. Zhigang Zhang
    240 Zhang
  3. Carol Portlock
    178 Portlock
  4. Craig Moskowitz
    368 Moskowitz
  5. Ariela Noy
    204 Noy
  6. Alexia Elia Iasonos
    179 Iasonos
  7. Andrew D Zelenetz
    546 Zelenetz
  8. Paul Hamlin
    170 Hamlin
  9. David J Straus
    205 Straus