Annals of Oncology Advance Access published online on March 6, 2008
Annals of Oncology, doi:10.1093/annonc/mdn018
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Bortezomib, doxorubicin and dexamethasone in advanced multiple myeloma
1 Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera S. Giovanni Battista, Torino
2 U.O. di Ematologia e Trapianto di Cellule Staminali, IRCCS Casa Sollievo della Sofferenza, S. Giovanni Rotondo
3 Divisione di Ematologia, Ospedale Centrale, Bolzano
4 Divisione di Ematologia, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria
5 Cattedra e Divisione di Ematologia, Università Tor Vergata, Ospedale San Eugenio, Roma
6 U.O.C. di Ematologia, Azienda Ospedaliera di Cosenza, Cosenza
7 U.O. di Ematologia e Trapianto di Cellule Staminali, CROB—Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture (Pz), Italy
* Correspondence to: Dr A. Palumbo, Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera S. Giovanni Battista, Via Genova 3, 10126 Torino, Italy. Tel: +39 0116635814; Fax: +39 0116963737; E-mail: appalumbo{at}yahoo.com
Background: Bortezomib has shown significant activity in myeloma. In this multicenter trial, we assessed for the first time the combination of bortezomib, doxorubicin and low-dose dexamethasone (PAd) in the treatment of relapsed/refractory myeloma.
Patients and methods: Sixty-four patients were treated for a median of four 28-day cycles (1–6). Bortezomib was given at 1.3 mg/m2 (days 1, 4, 8, 11) and dexamethasone at 40 mg (days 1–4); 34 patients receive doxorubicin at 20 mg/m2 (days 1, 4) while 30 patients pegylated liposomal doxorubicin at 30 mg/m2 (day 1).
Results: Fifty-eight percent of patients had undergone prior autologous transplantation, 70% prior anthracycline and 27% prior bortezomib-based regimens. Forty-three patients (67%) achieved at least a partial response including 16 (25%) with at least a very good partial response. One-year event-free survival was 34% after PAd and 31% after the previous line of therapy (hazard ratio 1.20, 95% confidence interval 0.76–1.90, P = 0.43). One-year overall survival from the start of PAd was 66%. Grade 3–4 toxic effects included thrombocytopenia (48%), neutropenia (36%), infections (15%), anemia (13%), gastrointestinal disturbances (11%) and peripheral neuropathy (10%). Two patients had grade 3–4 cardiac heart failure.
Conclusions: PAd is an active salvage therapy with manageable toxicity in patients with relapsed/refractory myeloma.
bortezomib, myeloma, relapse
Received for publication September 19, 2007. Revision received January 3, 2008. Accepted for publication January 4, 2008.
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