PMID- 29494421
OWN - NLM
STAT- MEDLINE
DCOM- 20190109
LR  - 20190109
IS  - 1536-3694 (Electronic)
IS  - 0163-4356 (Linking)
VI  - 40
IP  - 3
DP  - 2018 Jun
TI  - Phase II Clinical Trial of Lenalidomide and Dexamethasone Therapy in Japanese 
      Elderly Patients With Newly Diagnosed Multiple Myeloma to Determine Optimal 
      Plasma Concentration of Lenalidomide.
PG  - 301-309
LID - 10.1097/FTD.0000000000000499 [doi]
AB  - BACKGROUND: The authors conducted a phase II clinical trial of lenalidomide and 
      dexamethasone combination therapy in Japanese elderly patients with newly 
      diagnosed multiple myeloma to evaluate its safety and efficacy and to determine 
      whether safety and efficacy correlate with the plasma concentration of 
      lenalidomide. METHODS: Forty patients received oral lenalidomide on days 1-21 of 
      a 28-day cycle in addition to weekly doses of dexamethasone. Plasma 
      concentrations of lenalidomide were measured, and the area under the 
      concentration-time curve from 0 to 24 hours (AUC0-24) of lenalidomide was 
      predicted using a formula the authors previously reported in this journal. 
      RESULTS: The median age was 75.5 years. Twenty-one patients had renal impairment 
      severe enough to require dose adjustment of lenalidomide. The median initial 
      doses of lenalidomide and dexamethasone were 12.5 and 20 mg, respectively. The 
      overall response rate was 68.6%, and the 2-year overall survival rate was 88.5%. 
      There was no correlation between the response rate and plasma concentration of 
      lenalidomide. Grade 3-4 adverse events (AEs) were observed in 57.5% of patients. 
      The AUC0-24 of lenalidomide was significantly higher in patients with grade 3-4 
      AEs than in those who did not suffer from AEs (median = 4852.0 versus 2464.9 
      ng.h.mL, P = 0.027). Receiver-operating characteristic curve analysis showed that 
      the AUC0-24 of lenalidomide was a good predictor of grade 3-4 AEs, with an area 
      under the receiver-operating characteristic curve of 0.758 (95% confidence 
      interval, 0.572-0.943, P = 0.027). The cutoff value for best prediction of grade 
      3-4 AEs was 2613.5 ng.h.mL (sensitivity 86.7%, specificity 54.5%). Multivariate 
      logistic analysis confirmed the significance of this cutoff value. CONCLUSIONS: 
      These data suggest that overexposure to lenalidomide could contribute to 
      toxicity. Furthermore, the predicted cutoff value of AUC0-24 can be clinically 
      used to prevent severe AEs.
FAU - Kobayashi, Takahiro
AU  - Kobayashi T
AD  - Department of Hematology, Nephrology and Rheumatology, Akita University Graduate 
      School of Medicine.
FAU - Miura, Masatomo
AU  - Miura M
AD  - Department of Pharmacy, Akita University Hospital, Akita, Japan.
FAU - Niioka, Takenori
AU  - Niioka T
AD  - Department of Pharmacy, Akita University Hospital, Akita, Japan.
FAU - Abumiya, Maiko
AU  - Abumiya M
AD  - Department of Pharmacy, Akita University Hospital, Akita, Japan.
FAU - Ito, Fumiko
AU  - Ito F
AD  - Department of Hematology, Nephrology and Rheumatology, Akita University Graduate 
      School of Medicine.
FAU - Kobayashi, Isuzu
AU  - Kobayashi I
AD  - Department of Hematology, Nephrology and Rheumatology, Akita University Graduate 
      School of Medicine.
FAU - Ikeda, Sho
AU  - Ikeda S
AD  - Department of Hematology, Nephrology and Rheumatology, Akita University Graduate 
      School of Medicine.
FAU - Yoshioka, Tomoko
AU  - Yoshioka T
AD  - Department of Hematology, Nephrology and Rheumatology, Akita University Graduate 
      School of Medicine.
FAU - Kameoka, Yoshihiro
AU  - Kameoka Y
AD  - Department of Hematology, Nephrology and Rheumatology, Akita University Graduate 
      School of Medicine.
FAU - Takahashi, Naoto
AU  - Takahashi N
AD  - Department of Hematology, Nephrology and Rheumatology, Akita University Graduate 
      School of Medicine.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ther Drug Monit
JT  - Therapeutic drug monitoring
JID - 7909660
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Immunologic Factors)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - F0P408N6V4 (Lenalidomide)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Anti-Inflammatory Agents/administration & dosage/adverse effects/blood
MH  - Dexamethasone/*administration & dosage/adverse effects/*blood
MH  - Drug Monitoring/methods
MH  - Drug Therapy, Combination
MH  - Female
MH  - Follow-Up Studies
MH  - Hematologic Diseases/chemically induced
MH  - Humans
MH  - Immunologic Factors/administration & dosage/adverse effects/blood
MH  - Japan/epidemiology
MH  - Lenalidomide/*administration & dosage/adverse effects/*blood
MH  - Male
MH  - Multiple Myeloma/*blood/diagnosis/*drug therapy/epidemiology
MH  - Treatment Outcome
EDAT- 2018/03/02 06:00
MHDA- 2019/01/10 06:00
CRDT- 2018/03/02 06:00
PHST- 2018/03/02 06:00 [pubmed]
PHST- 2019/01/10 06:00 [medline]
PHST- 2018/03/02 06:00 [entrez]
AID - 10.1097/FTD.0000000000000499 [doi]
PST - ppublish
SO  - Ther Drug Monit. 2018 Jun;40(3):301-309. doi: 10.1097/FTD.0000000000000499.