Phase 2 study of pegylated liposomal doxorubicin, vincristine, decreased-frequency dexamethasone, and thalidomide in newly diagnosed and relapsed-refractory multiple myeloma.
OBJECTIVE
To evaluate the efficacy and safety of adding thalidomide to the pegylated liposomal doxorubicin, vincristine, and decreased-frequency dexamethasone (DVd) regimen for multiple myeloma.


METHODS
Patients newly diagnosed as having active multiple myeloma and those with relapsed-refractory disease were studied between August 2001 and October 2003. Patients received DVd as previously described. Thalidomide was given at 50 mg/d orally and the dose increased slowly to a maximum of 400 mg/d. At the time of best response, patients received maintenance prednisone, 50 mg orally every other day, and daily thalidomide at the maximum tolerated dose for each patient. The primary end point was the rate of complete responses plus very good partial responses as defined by the European Group for Blood and Marrow Transplantation criteria and the Intergroupe Français du Myélome, respectively.


RESULTS
Of 102 eligible patients, 53 were newly diagnosed as having multiple myeloma, and 49 had been previously treated for multiple myeloma. The complete response plus very good partial response rate was 49% and 45%, with an overall response rate of 87% and 90% for patients with newly diagnosed and previously treated multiple myeloma, respectively. Furthermore, better responses were associated with improved progression-free and overall survival. The most common grade 3 and 4 adverse events were thromboembolic events (25%), peripheral neuropathy (22%), and neutropenia (14%).


CONCLUSIONS
The addition of thalidomide to the DVd regimen significantly improves the response rate and quality of responses compared with the DVd regimen alone. This improvement is associated with longer progression-free and overall survival. The rate of observed quality responses is comparable to responses seen with high-dose therapy.
Hussein
Mohamad A
MA
Cleveland Clinic Myeloma Research Program, Cleveland Clinic Foundation, OH 44195, USA. mashussein@runbox.us
Baz
Rachid
R
Srkalovic
Gordan
G
Agrawal
Neeraj
N
Suppiah
Revathi
R
Hsi
Eric
E
Andresen
Steven
S
Karam
Mary Ann
MA
Reed
Janice
J
Faiman
Beth
B
Kelly
Megan
M
Walker
Esteban
E
D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012189:Retrospective Studies; D015996:Survival Rate; D013792:Thalidomide / Q000627:therapeutic use*; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D013792:Thalidomide; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin