PMID- 23497336
OWN - NLM
STAT- MEDLINE
DCOM- 20130828
LR  - 20211021
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 13
DP  - 2013 Mar 16
TI  - Results of a phase I dose escalation study of eltrombopag in patients with 
      advanced soft tissue sarcoma receiving doxorubicin and ifosfamide.
PG  - 121
LID - 10.1186/1471-2407-13-121 [doi]
AB  - BACKGROUND: The objective of this Phase I dose escalation study was to explore 
      the safety and tolerability of eltrombopag, an oral, nonpeptide, thrombopoietin 
      receptor agonist, in patients with advanced soft tissue sarcoma (STS) and 
      thrombocytopenia due to treatment with doxorubicin and ifosfamide (AI) 
      combination chemotherapy. METHODS: Patients aged 18 or older with histologically 
      confirmed, locally advanced or metastatic STS were treated with 1 cycle of AI 
      followed by AI with eltrombopag starting at Cycle 2, using 2 different dosing 
      schedules. The study design included an eltrombopag dose escalation phase 
      starting at 75 mg daily to determine the optimal biological dose (OBD). RESULTS: 
      Eighteen patients were enrolled and 15 received at least 1 dose of chemotherapy; 
      3 patients withdrew prior to receiving eltrombopag. Seven, 4, and 1 patients 
      received 75 mg, 100 mg, and 150 mg eltrombopag daily, respectively. No 
      dose-limiting toxicities were reported. Due to slow recruitment, the study was 
      closed prior to identifying an OBD. The most common hematologic adverse events 
      (AEs) were thrombocytopenia (80%), neutropenia (73%), and anemia (67%). The most 
      common nonhematologic AEs were fatigue (53%), alanine aminotransferase increased, 
      constipation, and nausea (47% each). Eleven of 12 patients who received 
      eltrombopag completed at least 2 chemotherapy cycles; all had increased platelet 
      counts on Day 1 of Cycle 2 (cycle with eltrombopag) compared to Day 1 of Cycle 1 
      (cycle without eltrombopag). CONCLUSIONS: Although data are limited, safety data 
      were consistent with the known toxicities of AI combination chemotherapy or the 
      side effect profile of eltrombopag seen in other studies. Available data suggest 
      a potential pre- and post-chemotherapy dosing scheme for eltrombopag when 
      administered with AI chemotherapy, and support further investigation of 
      eltrombopag treatment in patients with chemotherapy-induced thrombocytopenia.
FAU - Chawla, Sant P
AU  - Chawla SP
AD  - Sarcoma Oncology Center, Santa Monica, CA, USA.
FAU - Staddon, Arthur
AU  - Staddon A
FAU - Hendifar, Andrew
AU  - Hendifar A
FAU - Messam, Conrad A
AU  - Messam CA
FAU - Patwardhan, Rita
AU  - Patwardhan R
FAU - Kamel, Yasser Mostafa
AU  - Kamel YM
LA  - eng
SI  - ClinicalTrials.gov/NCT00358540
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130316
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzoates)
RN  - 0 (Hydrazines)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptors, Thrombopoietin)
RN  - 80168379AG (Doxorubicin)
RN  - S56D65XJ9G (eltrombopag)
RN  - UM20QQM95Y (Ifosfamide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/*administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Benzoates/*administration & dosage/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Doxorubicin/administration & dosage/adverse effects
MH  - Female
MH  - Humans
MH  - Hydrazines/*administration & dosage/adverse effects
MH  - Ifosfamide/administration & dosage/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Pyrazoles/*administration & dosage/adverse effects
MH  - Receptors, Thrombopoietin/*antagonists & inhibitors
MH  - Sarcoma/*drug therapy/pathology
MH  - Soft Tissue Neoplasms/*complications/drug therapy
MH  - Thrombocytopenia/chemically induced/*drug therapy
MH  - Young Adult
PMC - PMC3605142
EDAT- 2013/03/19 06:00
MHDA- 2013/08/29 06:00
PMCR- 2013/03/16
CRDT- 2013/03/19 06:00
PHST- 2012/04/12 00:00 [received]
PHST- 2013/03/06 00:00 [accepted]
PHST- 2013/03/19 06:00 [entrez]
PHST- 2013/03/19 06:00 [pubmed]
PHST- 2013/08/29 06:00 [medline]
PHST- 2013/03/16 00:00 [pmc-release]
AID - 1471-2407-13-121 [pii]
AID - 10.1186/1471-2407-13-121 [doi]
PST - epublish
SO  - BMC Cancer. 2013 Mar 16;13:121. doi: 10.1186/1471-2407-13-121.