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The addition of liposomal doxorubicin to bortezomib, thalidomide and dexamethasone significantly improves clinical outcome of advanced multiple myeloma
Author(s) -
Ciolli Stefania,
Leoni Franco,
Casini Cinzia,
Breschi Carla,
Santini Valeria,
Bosi Alberto
Publication year - 2008
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07147.x
Subject(s) - bortezomib , thalidomide , medicine , multiple myeloma , dexamethasone , regimen , doxorubicin , chemotherapy , toxicity , refractory (planetary science) , oncology , pharmacology , physics , astrobiology
Summary Relapsed/refractory myeloma has a poor outcome because of multi‐drug resistance, patient low‐performance status and toxicity of conventional chemotherapy. To improve results, standard chemotherapeutics and drugs targeting the microenvironment are applied at the same time. Bortezomib, by inhibiting proteasome function, may enhance chemosensitivity to other drugs and overcome drug‐resistance. Notably, doxorubicin and bortezomib may reciprocally increase their efficacy. Thus, to improve outcome whilst minimizing therapy‐related toxicity, liposomal doxorubicin was added to a bortezomib‐based combination. From January 2004, relapsed/refractory myeloma patients referred to our Institution received bortezomib 1·0 mg/m 2 i.v. twice weekly for 2 weeks in a 28‐d cycle for up to six cycles, oral dexamethasone 24 mg with the standard scheduling and thalidomide 100 mg continuously (VTD). From January 2005, liposomal doxorubicin, 50 mg/m 2 (30 mg/m 2 for patients older than 75 years), was added on day 4 of each cycle [VTD plus Myocet (MyVTD)]. In total, 70 patients were treated: 28 received VTD and 42 MyVTD. Baseline demographic and clinical characteristics were similar between the two groups. Toxicity was manageable although more pronounced with MyVTD. The overall response rate (81% vs. 50%, P = 0·009), time to progression (19 vs. 11 months, P = 0·01) and progression‐free survival (15 vs. 8 months, P = 0·001) were significantly higher with MyVTD regimen, suggesting an improved quality of response.