Long term results of a phase 2 study of vincristine sulfate liposome injection (Marqibo®) substituted for non-liposomal vincristine in cyclophosphamide, doxorubicin, vincristine, prednisone with or without rituximab for patients with untreated aggressive non-Hodgkin lymphomas Journal Article
| Authors: | Hagemeister, F.; Rodriguez, M. A.; Deitcher, S. R.; Younes, A.; Fayad, L.; Goy, A.; Dang, N. H.; Forman, A.; McLaughlin, P.; Medeiros, L. J.; Pro, B.; Romaguera, J.; Samaniego, F.; Silverman, J. A.; Sarris, A.; Cabanillas, F. |
| Article Title: | Long term results of a phase 2 study of vincristine sulfate liposome injection (Marqibo®) substituted for non-liposomal vincristine in cyclophosphamide, doxorubicin, vincristine, prednisone with or without rituximab for patients with untreated aggressive non-Hodgkin lymphomas |
| Abstract: | Vincristine sulfate liposome injection (VSLI; Marqibo®; M) is active in relapsed and refractory lymphomas, and approved in the United States for relapsed and refractory adult acute lymphocytic leukaemia. We evaluated VSLI (2·0 mg/m2 without dose cap) substituted for non-liposomal vincristine (VCR) in a cyclophosphamide, doxorubicin, vincristine, prednisone ± ritiximab (CHOP±R) regimen, creating CHMP±R in 72 untreated, aggressive non-Hodgkin lymphoma patients, including 60 with diffuse large B-cell lymphoma (DLBCL). The overall response rate was 96% (69/72) including complete response (CR) in 65 (90%) and unconfirmed CR in 2 (3%). Median progression-free survival (PFS) and overall survival (OS) were not reached at median follow-up of 8 and 10·2 years, respectively. The 5- and 10-year PFS and OS were 75%, 63%, 87%, and 77%, respectively. Despite VSLI exposure of up to 35 mg, the safety profile of CHMP±R was comparable to that reported for CHOP±R. Grade 3 peripheral neuropathy was reported in 2 (3%) patients; there was no reported Grade 3/4 constipation. CHMP±R was highly active, generally well tolerated, and compared favourably to historical trials with R-CHOP in DLBCL. This enhanced activity probably reflects VCR dose intensification, pharmacokinetic optimization, and enhanced delivery afforded by VSLI. A Phase 3 trial of R-CHMP versus R-CHOP in elderly patients with untreated DLBCL is ongoing. © 2013 John Wiley & Sons Ltd. |
| Keywords: | adult; treatment outcome; aged; aged, 80 and over; middle aged; survival analysis; young adult; major clinical study; overall survival; prednisone; constipation; fatigue; neutropenia; doxorubicin; diarrhea; drug dose reduction; drug safety; rituximab; drug megadose; follow up; progression free survival; multiple cycle treatment; phase 2 clinical trial; anemia; leukopenia; mucosa inflammation; nausea; thrombocytopenia; antineoplastic combined chemotherapy protocols; peripheral neuropathy; drug administration schedule; cyclophosphamide; vincristine; drug fever; dyspnea; febrile neutropenia; chemotherapy induced emesis; drug induced headache; hypokalemia; prednisolone; vincristine sulfate; nonhodgkin lymphoma; lymphoma, non-hodgkin; lymphoma; open study; weakness; large cell lymphoma; neurologic disease; gastrointestinal disease; metabolic disorder; thorax disease; liposome; liposomes; hematologic disease; respiratory tract disease; hypesthesia; sphingomyelin; lymphatic system disease; mouth ulcer; antibodies, monoclonal, murine-derived; mediastinum disease; nutritional disorder; dose intensification |
| Journal Title: | British Journal of Haematology |
| Volume: | 162 |
| Issue: | 5 |
| ISSN: | 0007-1048 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2013-09-01 |
| Start Page: | 631 |
| End Page: | 638 |
| Language: | English |
| DOI: | 10.1111/bjh.12446 |
| PROVIDER: | scopus |
| PUBMED: | 23802738 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 September 2013" - "CODEN: BJHEA" - "Source: Scopus" |
