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 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 23 June 2011" - "CODEN: CCREF" - "Source: Scopus" |
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