PMID- 36212431
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221011
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 12
DP  - 2022
TI  - Treatment related toxicities with combination BRAF and MEK inhibitor therapy in 
      resected stage III melanoma.
PG  - 855794
LID - 10.3389/fonc.2022.855794 [doi]
LID - 855794
AB  - Combination dabrafenib (D) and trametinib (T) is an FDA approved adjuvant therapy 
      for patients with resected stage III BRAF-mutant melanoma. We describe 
      treatment-related toxicities with adjuvant D+T in a real-world population through 
      a retrospective case series. The primary endpoint was development of toxicities. 
      RESULTS: Eighteen of the 20 patients (90%) required at least one treatment 
      interruption due to adverse events (AEs), 11 patients (55%) required a dose 
      reduction and 13 (65%) permanently discontinued therapy due to an AE. The nine 
      patients who did not require dose reduction had been initiated on a lower 
      starting dose of dabrafenib. The most common treatment-limiting AEs were 
      recurrent pyrexia and chills (85%) and liver laboratory abnormalities (50%). The 
      median total time on therapy was 148.5 days (range 19-383), 40.7% (range 
      5.2-100%) of the intended one-year duration. CONCLUSION: Adjuvant treatment of 
      melanoma with combination D+T is associated with treatment-limiting toxicities in 
      the majority of this patient group. Patients should be carefully monitored 
      throughout therapy.
CI  - Copyright (c) 2022 Homan, Warrier, Lao, Yentz, Kraft and Fecher.
FAU - Homan, Morgan
AU  - Homan M
AD  - Department of Pharmacy, University of Michigan, Ann Arbor, MI, United States.
FAU - Warrier, Govind
AU  - Warrier G
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United 
      States.
FAU - Lao, Christopher D
AU  - Lao CD
AD  - Department of Internal Medicine and Dermatology, University of Michigan, Ann 
      Arbor, MI, United States.
FAU - Yentz, Sarah
AU  - Yentz S
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United 
      States.
FAU - Kraft, Shawna
AU  - Kraft S
AD  - Department of Pharmacy, University of Michigan, Ann Arbor, MI, United States.
FAU - Fecher, Leslie A
AU  - Fecher LA
AD  - Department of Internal Medicine and Dermatology, University of Michigan, Ann 
      Arbor, MI, United States.
LA  - eng
PT  - Journal Article
DEP - 20220923
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC9538392
OTO - NOTNLM
OT  - BRAF
OT  - MEK
OT  - inhibitor
OT  - melanoma
OT  - pyrexia
OT  - toxicity
COIS- LF: institutional funding for clinical trials (site PI) from Array/Pfizer, 
      Bristol Myers Squibb, EMD Serono, Kartos. Consultant for Elsevier. Array/Pfizer 
      funding of ECOG-ACRIN clinical trial (national PI) for LAF. The remaining authors 
      declare that the research was conducted in the absence of any commercial or 
      financial relationships that could be construed as a potential conflict of 
      interest.
EDAT- 2022/10/11 06:00
MHDA- 2022/10/11 06:01
PMCR- 2022/01/01
CRDT- 2022/10/10 04:12
PHST- 2022/01/16 00:00 [received]
PHST- 2022/08/16 00:00 [accepted]
PHST- 2022/10/10 04:12 [entrez]
PHST- 2022/10/11 06:00 [pubmed]
PHST- 2022/10/11 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2022.855794 [doi]
PST - epublish
SO  - Front Oncol. 2022 Sep 23;12:855794. doi: 10.3389/fonc.2022.855794. eCollection 
      2022.