PMID- 26331915
OWN - NLM
STAT- MEDLINE
DCOM- 20170206
LR  - 20170206
IS  - 1600-0609 (Electronic)
IS  - 0902-4441 (Linking)
VI  - 97
IP  - 1
DP  - 2016 Jul
TI  - 'Real-life' experience of preapproval carfilzomib-based therapy in myeloma - 
      analysis of cardiac toxicity and predisposing factors.
PG  - 25-32
LID - 10.1111/ejh.12677 [doi]
AB  - BACKGROUND: Carfilzomib, the second-generation proteasome inhibitor, is still 
      awaiting approval for the treatment of multiple myeloma in Europe. Results from 
      clinical trials have demonstrated favorable efficacy in advanced disease but have 
      opened an ongoing debate on cardiac complications related to carfilzomib 
      treatment. 'Real-life' data are scarce. METHODS/PATIENTS: At our institution, 22 
      patients were registered within the European Carfilzomib Access Program for 
      treatment with carfilzomib, dexamethasone, and a third combination partner 
      depending on patient characteristics and prior treatment. Patients had received a 
      median of six previous lines of therapy, and most were refractory to bortezomib 
      (77%) and immunomodulatory drugs (95%). RESULTS: Overall response rate was 65% 
      with a median progression-free survival of 6.0 months and a median duration of 
      response of 6.8 months. Median overall survival was 14.9 months. Grade 3/4 
      adverse events (AEs) occurred in 50% of patients with 23% experiencing left 
      ventricular failure. The risk of cardiac AEs was markedly increased after 
      previous radiotherapy of the thoracic spine and concomitant administration of 
      doxorubicin. CONCLUSION: Carfilzomib-based treatment is efficient in advanced 
      multiple myeloma. In our 'real-life' patients, we found considerable cardiotoxic 
      effects in some cases, indicating a need for careful patient selection and close 
      monitoring of the at-risk population.
CI  - (c) 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Danhof, Sophia
AU  - Danhof S
AD  - Division of Hematology and Medical Oncology, Department of Internal Medicine, 
      Wuerzburg University Medical Center, Wuerzburg, Germany.
FAU - Schreder, Martin
AU  - Schreder M
AD  - Division of Hematology and Medical Oncology, Department of Internal Medicine, 
      Wuerzburg University Medical Center, Wuerzburg, Germany.
FAU - Rasche, Leo
AU  - Rasche L
AD  - Division of Hematology and Medical Oncology, Department of Internal Medicine, 
      Wuerzburg University Medical Center, Wuerzburg, Germany.
FAU - Strifler, Susanne
AU  - Strifler S
AD  - Division of Hematology and Medical Oncology, Department of Internal Medicine, 
      Wuerzburg University Medical Center, Wuerzburg, Germany.
FAU - Einsele, Hermann
AU  - Einsele H
AD  - Division of Hematology and Medical Oncology, Department of Internal Medicine, 
      Wuerzburg University Medical Center, Wuerzburg, Germany.
FAU - Knop, Stefan
AU  - Knop S
AD  - Division of Hematology and Medical Oncology, Department of Internal Medicine, 
      Wuerzburg University Medical Center, Wuerzburg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20150921
PL  - England
TA  - Eur J Haematol
JT  - European journal of haematology
JID - 8703985
RN  - 0 (Oligopeptides)
RN  - 0 (Proteasome Inhibitors)
RN  - 72X6E3J5AR (carfilzomib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Cardiotoxicity
MH  - Clinical Trials as Topic
MH  - Combined Modality Therapy
MH  - Disease Susceptibility
MH  - Drug Approval
MH  - Drug Resistance, Neoplasm
MH  - Europe
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/diagnosis/*drug therapy/mortality
MH  - Oligopeptides/administration & dosage/adverse effects
MH  - Proteasome Inhibitors/administration & dosage/adverse effects
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Treatment Outcome
OTO - NOTNLM
OT  - cardiac toxicity
OT  - carfilzomib
OT  - doxorubicin
OT  - heavily pretreated patients
OT  - multiple myeloma
OT  - proteasome inhibition
OT  - radiotherapy
EDAT- 2015/09/04 06:00
MHDA- 2017/02/07 06:00
CRDT- 2015/09/03 06:00
PHST- 2015/08/25 00:00 [accepted]
PHST- 2015/09/03 06:00 [entrez]
PHST- 2015/09/04 06:00 [pubmed]
PHST- 2017/02/07 06:00 [medline]
AID - 10.1111/ejh.12677 [doi]
PST - ppublish
SO  - Eur J Haematol. 2016 Jul;97(1):25-32. doi: 10.1111/ejh.12677. Epub 2015 Sep 21.