PMID- 29218462
OWN - NLM
STAT- MEDLINE
DCOM- 20190319
LR  - 20200409
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 168
IP  - 2
DP  - 2018 Apr
TI  - A single institution experience with palbociclib toxicity requiring dose 
      modifications.
PG  - 381-387
LID - 10.1007/s10549-017-4606-9 [doi]
AB  - PURPOSE: Since the widespread implementation of adding palbociclib to endocrine 
      therapy in clinical practice, myelosuppression is becoming increasingly 
      recognized as a toxicity that may lead to dose modification. We aimed to 
      characterize toxicities observed with palbociclib resulting in dose modifications 
      and prescriber preferences in modifying palbociclib dosage in response to 
      treatment-related toxicities outside the context of a clinical trial. METHODS: We 
      conducted a single institution, retrospective study of treatment-related adverse 
      events (AEs) resulting in modifications in dose and schedule and the methods by 
      which dose modifications occurred in patients with advanced hormone receptor 
      (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast 
      cancer receiving palbociclib and endocrine therapy. RESULTS: From 2/2015 to 
      10/2016, 100 patients were identified for inclusion in this study. Treatment with 
      palbociclib and endocrine therapy resulted in dose modifications in 38.0% of 
      patients due to AEs with 18.4% requiring subsequent dose changes. Most 
      palbociclib dose modifications occurred during the first 2 cycles. Grade 3-4 
      neutropenia accounted for 54.8% events of palbociclib dose modification. Most 
      providers (65.8%) dose reduced palbociclib from 125 mg to 100 mg as their 
      preferred method of dose modification, while others dose reduced from 125 mg to 
      75 mg (10.5%) and altered the schedule to 125 mg every other day (7.9%). A 
      comparable rate of palbociclib dose modifications and subsequent dose changes 
      were identified in an age >/= 65 subgroup. In this group, dose adjustments were 
      most commonly from grade 3-4 neutropenia, occurred mainly during cycle 1, and 
      were most frequently addressed by dose reduction from 125 to 100 mg. CONCLUSIONS: 
      Neutropenia remains the predominant cause for palbociclib dose modification and 
      most modifications occur within the first two cycles. Older age (>/= 65) does not 
      affect palbociclib tolerance. Our findings provide context outside of a clinical 
      trial that inform ongoing studies evaluating the safety and feasibility of 
      palbociclib-based therapies.
FAU - Gong, Jun
AU  - Gong J
AD  - Department of Medical Oncology and Therapeutics Research, City of Hope 
      Comprehensive Cancer Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA.
FAU - Cho, May
AU  - Cho M
AD  - Department of Medical Oncology and Therapeutics Research, City of Hope 
      Comprehensive Cancer Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA.
FAU - Yu, Kim Wai
AU  - Yu KW
AD  - Department of Medical Oncology and Therapeutics Research, City of Hope 
      Comprehensive Cancer Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA.
FAU - Waisman, James
AU  - Waisman J
AD  - Department of Medical Oncology and Therapeutics Research, City of Hope 
      Comprehensive Cancer Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA.
FAU - Yuan, Yuan
AU  - Yuan Y
AD  - Department of Medical Oncology and Therapeutics Research, City of Hope 
      Comprehensive Cancer Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA.
FAU - Mortimer, Joanne
AU  - Mortimer J
AUID- ORCID: 0000-0002-2935-1934
AD  - Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer 
      Center, Building 51, Room 122, 1500 E Duarte Rd, Duarte, CA, 91010, USA. 
      jmortimer@coh.org.
LA  - eng
GR  - K12 CA138464/CA/NCI NIH HHS/United States
GR  - P30 CA093373/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20171207
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Piperazines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Estrogen)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - G9ZF61LE7G (palbociclib)
SB  - IM
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents, Hormonal/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse 
      effects
MH  - Breast Neoplasms/*drug therapy/pathology
MH  - Chemotherapy-Induced Febrile Neutropenia/*epidemiology/etiology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - Piperazines/administration & dosage/*adverse effects
MH  - Protein Kinase Inhibitors/administration & dosage/*adverse effects
MH  - Pyridines/administration & dosage/*adverse effects
MH  - Receptor, ErbB-2/metabolism
MH  - Receptors, Estrogen/metabolism
MH  - Retrospective Studies
PMC - PMC5838140
OTO - NOTNLM
OT  - Breast cancer
OT  - Dose modification
OT  - Hormone receptor positive
OT  - Neutropenia
OT  - Palbociclib
OT  - Postmenopausal
COIS- Authors declare no conflict of interest.
EDAT- 2017/12/09 06:00
MHDA- 2019/03/20 06:00
PMCR- 2017/12/07
CRDT- 2017/12/09 06:00
PHST- 2017/08/31 00:00 [received]
PHST- 2017/11/30 00:00 [accepted]
PHST- 2017/12/09 06:00 [pubmed]
PHST- 2019/03/20 06:00 [medline]
PHST- 2017/12/09 06:00 [entrez]
PHST- 2017/12/07 00:00 [pmc-release]
AID - 10.1007/s10549-017-4606-9 [pii]
AID - 4606 [pii]
AID - 10.1007/s10549-017-4606-9 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2018 Apr;168(2):381-387. doi: 10.1007/s10549-017-4606-9. 
      Epub 2017 Dec 7.