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A Phase II trial of pegylated liposomal doxorubicin, vincristine, and reduced‐dose dexamethasone combination therapy in newly diagnosed multiple myeloma patients
Author(s) -
Hussein Mohamad A.,
Wood Laura,
Hsi Eric,
Srkalovic Gordan,
Karam MaryAnn,
Elson Paul,
Bukowski Ronald M.
Publication year - 2002
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.10946
Subject(s) - medicine , vincristine , regimen , doxorubicin , mucositis , dexamethasone , cardiotoxicity , chemotherapy , neutropenia , surgery , gastroenterology , oncology , pharmacology , cyclophosphamide
Abstract 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. Cancer 2002;95:2160–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10946