Cyclophosphamide, etoposide, vincristine, adriamycin, and dexamethasone (CEVAD) regimen in refractory multiple myeloma: An international oncology study group (IOSG) phase II protocol

Abstract

A 4- day continuous intravenous (CIV) infusion of vincristine and doxorubicin with high-dose dexamethasone (VAD) regimen is a standard refractory multiple myeloma (MM) regimen. A Phase II study of a CEVAD regimen, i.e., VAD plus etoposide administered as a 96-hr continuous infusion, was carried out with IV bolus cyclophosphamide. Thirty-six patients were treated on study and received a total of 114 cycles of CEVAD: median 2 cycles (range 1-8). No patient achieved a CR. The overall rate of PR was 15/36 (42%). Patients achieved maximal response after a median of 4 (range 3-6) courses. PR rates were 40% (4/10) in patients with primary refractory disease, 48% (11/23) in patients with secondary refractory disease, 31% (6/19) in patients who had failed previous VAD therapy, and 50% (7/14) in patients receiving 2nd or subsequent relapse therapy. Three patients died during their initial cycle of therapy from rapidly progressive disease and sepsis. Overall median survival was 24 weeks with a 1-year survival of 33.3% ¿95% confidence interval of 20-46%¿. Myelosuppression was the most frequent adverse event with NCI grade 2 neutropenia and/or thrombocytopenia in 15% of first cycles, grade 3 in 20%, and grade 4 in 65%. Two-thirds of patients had at least one episode of grade 3 or 4 sepsis. In 15% of septic episodes positive blood cultures were obtained. Overt cardiotoxicity was seen in two patients. CEVAD as used in this study was not more effective than VAD in terms of overall response rate or survival.

The use of novel agents in the treatment of relapsed and refractory multiple myeloma

“…Conventional chemotherapeutic regimens used in this context have included high-dose dexamethasone; 1,2 vincristine, doxorubicin and dexamethasone; 3–7 vincristine, melphalan, cyclophosphamide, prednisone/vincristine, carmustine, doxorubicin and prednisone; 8 and doxorubicin, vincristine, dexamethasone, etoposide and cyclophosphamide. 9 The use of high-dose melphalan in relapsed MM, meanwhile, was introduced over 20 years ago by Barlogie et al . 10,11 , who showed that myeloablative doses of melphalan with stem cell support could overcome resistance to conventional-dose chemotherapy in this group of patients.…”

Cardiac toxicities in multiple myeloma: an updated and a deeper look into the effect of different medications and novel therapies

“…Previously, Sunami et al had reported results from a phase I/II study of sequential VAD, high dose cyclophosphamide utilized for stem cell mobilization, followed by tandem autologous stem cell transplant (ASCT) using melphalan conditioning in a total of 40 patients, noting only 2 unspecified grade III CV toxicity events during induction with VAD, and 1 event post first transplant but none during high dose cyclophosphamide, or the second tandem transplant [ 10 ]. Similarly, the intensive chemotherapy regimen CEVAD (cyclophosphamide, etoposide, vincristine, Adriamycin, dexamethasone) was associated with around 5.5% cardiotoxicity (2 out of 36 patients, both of whom were previously treated with high doses of adriamycin) [ 11 ]. Autologous stem cell transplant using high dose melphalan still plays an important role in the management of newly diagnosed and relapsed disease.…”

The Role of Bortezomib, Thalidomide and Lenalidomide in the Management of Multiple Myeloma

“…[45] Likewise, doxorubicin plus dexamethasone has been used in combination with other drugs such as melphalan, cyclophosphamide, carmustine, etoposide, cisplatin and thalidomide. [1,[46][47][48] …”