ABSTRACT
Our previous studies have shown that lowering the dose of pegylated liposomal doxorubicin (PLD) and bortezomib in combination with intravenous dexamethasone on a longer 4-week cycle maintained efficacy and improved tolerability in both previously untreated and relapsed/refractory (R/R) multiple myeloma (MM) patients. Lenalidomide has shown efficacy in combination with bortezomib and dexamethasone but this combination has been poorly tolerated. We conducted this phase 2 study (clinicaltrials.gov identifier: NCT01160484) to evaluate whether a longer 4-week schedule using modified doses and schedules of IV dexamethasone (40 mg), bortezomib (1.0 mg/m(2)) and PLD (4.0 mg/m(2)) administered on days 1, 4, 8, and 11 with lenalidomide 10 mg daily on days 1-14 (DVD-R) would be effective and tolerated for patients with R/R MM. A total of 40 heavily pretreated patients were enrolled and 84.6% showed clinical benefit (complete response, 20.5%; very good partial response, 10.3%; partial response, 17.9%; minimal response, 35.9%) to the combination regimen. An additional 10.3% showed stable disease and 5.1% progressed while on study. The regimen was well tolerated, with a low incidence of adverse events such as fatigue (40%), thrombocytopenia (35%), neutropenia (35%), anemia (30%), peripheral neuropathy (25%) and pneumonia (15%). Thus, the DVD-R regimen is well tolerated and produces high response rates for patients with R/R MM.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Multiple Myeloma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Salvage Therapy , Adult , Aged , Aged, 80 and over , Boronic Acids/administration & dosage , Bortezomib , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Doxorubicin/analogs & derivatives , Drug Resistance, Neoplasm , Female , Follow-Up Studies , Humans , Lenalidomide , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Polyethylene Glycols/administration & dosage , Prognosis , Prospective Studies , Pyrazines/administration & dosage , Survival Rate , Thalidomide/administration & dosage , Thalidomide/analogs & derivativesABSTRACT
Over the past decade, the ever-increasing volume of evidence implicating HPV types in genital neoplasia has stimulated much research interest into all aspects of the biology of this interesting group of viruses. This research has led to the identification of growing heterogeneity of HPV types. It is not surprising, therefore, that the clinical profile of disease associated with genital HPV types is much broader than previously recognized. Knowledge of this clinical spectrum is mandatory to the understanding of the possible role of specific HPV types in human carcinogenesis.