A Phase II trial of pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone combination therapy in newly diagnosed multiple myeloma patients.
BACKGROUND
Patients with multiple myeloma (MM) have increased bone marrow angiogenesis, a low plasma cell labeling index, and multidrug resistance (the primary cause of chemotherapy failure). MM patients receiving the vincristine, doxorubicin, and dexamethasone (VAD) regimen develop resistance and cardiac and steroid toxicity. Pegylated liposomal doxorubicin (Doxil/CAELYX) could potentially extend the duration of malignant plasma cell exposure to therapeutic levels of doxorubicin. This Phase II study evaluates combination pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone in MM patients.


METHODS
Thirty-three newly diagnosed patients with MM received intravenous pegylated liposomal doxorubicin (40 mg/m(2)), vincristine (2.0 mg, Day 1), and oral or intravenous dexamethasone (40 mg per day for 4 days) every 4 weeks for six or more cycles and/or for two cycles after the best response.


RESULTS
The overall response rate was 88%: 4 (12%) patients achieved a complete response, 18 (55%) a major response, and 7 (21%) a minor response. Three patients (9%) had stable and one (3%) had progressive disease. The median time to progression was 23.1 months, with 2-year and 3-year progression-free survival rates of 42% and 23%, respectively. The patient survival rate at 3 years was 67%. No patients discontinued treatment due to adverse events. Myelosuppression was manageable. The most common toxicities were Grade 3 palmar-plantar erythrodysesthesia, mucositis, and neutropenia. Only one patient experienced cardiotoxicity.


CONCLUSIONS
Substituting pegylated liposomal doxorubicin for doxorubicin in the VAD regimen and reducing the dose of dexamethasone in patients with MM improve the safety profile and convenience of the treatment regimen without compromising efficacy.
Hussein
Mohamad A
MA
Myeloma Research Program, Cleveland Clinic Taussig Center, Cleveland, Ohio 44195, USA. husseim@ccf.org
Wood
Laura
L
Hsi
Eric
E
Srkalovic
Gordan
G
Karam
MaryAnn
M
Elson
Paul
P
Bukowski
Ronald M
RM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000209:etiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy*; D009503:Neutropenia / Q000209:etiology; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage* / Q000009:adverse effects
D008081:Liposomes; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin