A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma.

Abstract

Bortezomib-containing combinations are active in non-Hodgkin lymphoma (NHL) although peripheral neuropathy can limit their dose intensity. Based on our phase I findings, we conducted a phase II trial of bortezomib in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with a modified dose of vincristine. Patients with untreated indolent NHL received bortezomib (1·6 mg/m(2) ) on days 1 and 8 of a 21-day cycle for up to 8 cycles and R-CHOP with a 1·5 mg cap of vincristine. Patients achieving a complete response (CR) received maintenance rituximab, and remaining patients received maintenance rituximab and bortezomib. The primary endpoint was CR rate; secondary survival analyses were evaluated using the Kaplan-Meier method. Among 29 eligible patients, NHL morphologies included follicular (n = 20), marginal zone (n = 5) and small lymphocytic lymphoma (n = 4). Nineteen patients had CR (66%) and 10 had partial response (34%), yielding a 100% overall response rate. With a median follow-up of 48·7 months, the 4-year progression-free and overall survivals were 83% and 93%. Twenty-two patients experienced peripheral neuropathy of any grade, and two had grade 3 neuropathy. The combination of bortezomib with R-CHOP is effective for indolent NHL, and we plan to evaluate therapies incorporating novel proteasome inhibitors in future studies in NHL.

• Authors: Jonathon B Cohen, Jeffrey M Switchenko, Jean L Koff, Rajni Sinha, Jonathan L Kaufman, H Jean Khoury, Nassoma Bumpers, Amanda Colbert, Amanda Hutchison-Rzepka, Loretta J Nastoupil, Leonard T Heffner, Amelia A Langston, Mary Jo Lechowicz, Sagar Lonial, Christopher R Flowers
• Journal: British journal of haematology (Br J Haematol) Vol. 171 Issue 4 Pg. 539-46 (Nov 2015) ISSN: 1365-2141 [Electronic] England
• PMID: 26248505 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• Rituximab
• Vincristine
• Bortezomib
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Bortezomib (adverse effects, therapeutic use)
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Doxorubicin (administration & dosage)
• Female
• Follow-Up Studies
• Gastrointestinal Diseases (chemically induced)
• Humans
• Kaplan-Meier Estimate
• Lymphoma, Follicular (drug therapy)
• Lymphoma, Non-Hodgkin (drug therapy)
• Male
• Middle Aged
• Peripheral Nervous System Diseases (chemically induced)
• Prednisone (administration & dosage)
• Rituximab (adverse effects, therapeutic use)
• Thrombocytopenia (chemically induced)
• Treatment Outcome
• Vincristine (administration & dosage)