The proposed regimen is supported by a variety of data and is FDA approved. Oakervee et al.investigated the addition of doxorubicin to bortezomib and dexamethasone (PAD) as induction therapy prior to HDT-SCT. In this ongoing phase II trial, data are available from 21 patients. After PAD induction, the ORR was 95%, including a 29% CR/nCR rate. Following HDT-SCT, the ORR remained the same but the CR/nCR rate increased to 57% . These investigators also evaluated a modified PAD regimen, incorporating a lower dose of bortezomib, with the aim of reducing the incidence of peripheral neuropathy and other toxicities. The ORR among 19 evaluable patients was 89%, including a 16% CR/nCR rate. Among 13 patients receiving HDT-SCT, the ORR post-transplant was 100%, with a 54% CR/nCR rate. These preliminary data suggest that PAD is an effective induction regimen prior to HDT-SCT.
The Cancer and Leukemia Group B (CALGB) investigated the combination of bortezomib plus liposomal doxorubicin in a phase II clinical trial. Of 63 patients enrolled, response data are available for 29 patients who have completed study therapy; the ORR was 79%, with a 28% CR/nCR rate. Key grade 3 hematologic toxicities included neutropenia, thrombocytopenia, lymphopenia, and anemia.
The addition of liposomal doxorubicin to bortezomib and dexamethasone (VDD) was investigated in a phase II study. Among 28 evaluable patients the ORR was 89%, including a 32% CR/nCR rate. Seventeen patients proceeded to HDT-SCT, resulting in an improved response in 11 and increasing the ORR to 96% and the CR/nCR rate to 54%. Grade 3 hematologic toxicities included thrombocytopenia and neutropenia
The US Food and Drug Administration (FDA) announced on May 17, 2007 the approval of Doxil (liposomal doxorubicin) plus Velcade (vortezomib) for the treatment of patients with multiple myeloma who had failed at least one prior regimen and had not been treated with Velcade. To date, data from more than 900 patients have been reported from 15 clinical trials investigating the role of bortezomib, as a single agent and in combination with other agents, in the frontline treatment of multiple myeloma.
I should aslo mention that Doxil is a liposomal preparation of doxorubicin, which has already been addressed above and has phase II study support.
Rami Manochakian, Kena C. Miller, Asher A. Chanan-Khan Clinical Impact of Bortezomib in Frontline Regimens for Patients with Multiple Myeloma The Oncologist, Vol. 12, No. 8, 978-990, August 2007;
Orlowski RZ, Peterson BL, Sanford B et al. Bortezomib and pegylated liposomal doxorubicin as induction therapy for adult patients with symptomatic multiple myeloma: Cancer and Leukemia Group B Study 10301. Updated data presented at the 2006 Annual Meeting of the American Society of Hematology. Blood 2006;108:239a.
Jakubowiak AJ, Al-Zoubi A, Kendall T et al. High rate of complete and near complete responses (CR/nCR) after initial therapy with bortezomib (Velcade), Doxil, and dexamethasone (VDD) is further increased after autologous stem cell transplantation (ASCT). Updated data presented at the 2006 Annual Meeting of the American Society of Hematology. Blood 2006;108:882a.