Τίτλος:
Phase II study of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide for sub-optimal response as second-line treatment for patients with multiple myeloma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
This phase II study is the first prospective evaluation of bortezomib-dexamethasone as second-line therapy for relapsed/refractory multiple myeloma. A total of 163 patients were enrolled to receive four cycles of bortezomibdexamethasone. Patients were investigator-assessed for response at cycle 5 Day 1, then treated as follows: responding patients received another four cycles of bortezomib-dexamethasone, while patients with stable disease were subsequently randomized to sequential treatment with a further four cycles of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide. The primary end point was response to sequential therapy; however, this could not be evaluated because investigator-assessed response rates to bortezomib-dexamethasone after four cycles were high, and an insufficient number of patients were randomized to sequential treatment per protocol. Among all 163 patients, validated best confirmed response rate was 66%, including 37% complete/very good partial responses; median response duration was 9.7 months. After a median follow up of 16.9 months, median time to progression and progression-free survival were 9.5 and 8.6 months, respectively; estimated 1-year overall survival was 81%. Median glomerular filtration rate improved from baseline during treatment. Among 58 patients with baseline glomerular filtration rate below 50 mL/min, 24 had renal responses. Grade 3/4 adverse events included: thrombocytopenia (17%), anemia (10%), constipation (6%), peripheral sensory neuropathy (5%), and polyneuropathy (5%). Overall, 57% of neuropathy events improved/resolved; median time to improvement was 2.1 months. These findings suggest bortezomib-dexamethasone represents an active, feasible second-line treatment option for patients with relapsed/refractory myeloma.. © 2013 Ferrata Storti Foundation.
Συγγραφείς:
Dimopoulos, M.A.
Beksac, M.
Benboubker, L.
Roddie, H.
Allietta, N.
Broer, E.
Couturier, C.
Mazier, M.-A.
Angermund, R.
Facon, T.
Περιοδικό:
Haematologica-the hematology journal
Λέξεις-κλειδιά:
bortezomib; cyclophosphamide; dexamethasone; doxorubicin; lenalidomide; melphalan; prednisolone; prednisone; thalidomide; vincristine, adult; aged; anemia; article; constipation; controlled study; drug efficacy; drug safety; drug withdrawal; female; follow up; glomerulus filtration rate; human; kidney function; major clinical study; male; multiple cycle treatment; multiple myeloma; neuralgia; neutropenia; parallel design; peripheral neuropathy; phase 2 clinical trial; pneumonia; polyneuropathy; randomized controlled trial; sensory neuropathy; thrombocytopenia, Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Cyclophosphamide; Dexamethasone; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multiple Myeloma; Prospective Studies; Pyrazines; Thalidomide; Treatment Outcome
DOI:
10.3324/haematol.2013.084376
