PMID- 25446280
OWN - NLM
STAT- MEDLINE
DCOM- 20150324
LR  - 20220408
IS  - 1545-5017 (Electronic)
IS  - 1545-5009 (Print)
IS  - 1545-5009 (Linking)
VI  - 62
IP  - 3
DP  - 2015 Mar
TI  - Phase II study of cixutumumab in combination with temsirolimus in pediatric 
      patients and young adults with recurrent or refractory sarcoma: a report from the 
      Children's Oncology Group.
PG  - 440-4
LID - 10.1002/pbc.25334 [doi]
AB  - BACKGROUND: The combined inhibition of insulin-growth factor type 1 receptor 
      (IGF-1R) and the mammalian target of rapamycin (mTOR) has shown activity in 
      preclinical models of pediatric sarcoma and in adult sarcoma patients. We 
      evaluated the activity of the anti-IGF-1R antibody cixutumumab with the mTOR 
      inhibitor temsirolimus in patients with relapsed or refractory Ewing sarcoma, 
      osteosarcoma, rhabdomyosarcoma, and other soft tissue sarcoma, using the 
      recommended dosages from a pediatric phase I trial. METHODS: Cixutumumab 6 mg/kg 
      and temsirolimus 8 mg/m(2) were administered intravenously once weekly in 4-week 
      cycles to patients <30 years. Temsirolimus was escalated to 10 mg/m(2) for 
      subsequent cycles in patients who did not experience unacceptable first-cycle 
      toxicity. A two-stage design was used to identify a response rate <10 or >35% for 
      each tumor-specific cohort. Tumor tissue was analyzed by immunohistochemistry for 
      potential biomarkers of response. RESULTS: Forty-three evaluable patients 
      received a median of 2 cycles (range 1-7). No objective responses were observed, 
      and 16% of patients were progression-free at 12 weeks. Dose-limiting toxicity was 
      observed in 15 (16%) of 92 cycles. The most common toxicities were mucositis, 
      electrolyte disturbances, and myelosuppression. The majority of patients 
      receiving a second cycle were not eligible for temsirolimus escalation due to 
      first-cycle toxicity. The lack of objective responses precluded correlation with 
      tissue biomarkers. CONCLUSIONS: Despite encouraging preclinical data, the 
      combination of cixutumumab and temsirolimus did not result in objective responses 
      in this phase II trial of pediatric and young adults with recurrent or refractory 
      sarcoma.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Wagner, Lars M
AU  - Wagner LM
AD  - Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, 
      Ohio.
FAU - Fouladi, Maryam
AU  - Fouladi M
FAU - Ahmed, Atif
AU  - Ahmed A
FAU - Krailo, Mark D
AU  - Krailo MD
FAU - Weigel, Brenda
AU  - Weigel B
FAU - DuBois, Steven G
AU  - DuBois SG
FAU - Doyle, L Austin
AU  - Doyle LA
FAU - Chen, Helen
AU  - Chen H
FAU - Blaney, Susan M
AU  - Blaney SM
LA  - eng
GR  - CA98543/CA/NCI NIH HHS/United States
GR  - CA180899/CA/NCI NIH HHS/United States
GR  - U10 CA098413/CA/NCI NIH HHS/United States
GR  - CA180886/CA/NCI NIH HHS/United States
GR  - U10 CA098543/CA/NCI NIH HHS/United States
GR  - U10 CA180899/CA/NCI NIH HHS/United States
GR  - CA98413/CA/NCI NIH HHS/United States
GR  - U10 CA180886/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
DEP - 20141128
PL  - United States
TA  - Pediatr Blood Cancer
JT  - Pediatric blood & cancer
JID - 101186624
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Biomarkers, Tumor)
RN  - 2285XW22DR (cixutumumab)
RN  - 624KN6GM2T (temsirolimus)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Monoclonal/*administration & dosage/adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage
MH  - Biomarkers, Tumor/*metabolism
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Humans
MH  - Infant
MH  - Male
MH  - *Sarcoma/drug therapy/metabolism/pathology
MH  - Sirolimus/administration & dosage/adverse effects/*analogs & derivatives
MH  - Young Adult
PMC - PMC4501773
MID - NIHMS635278
OTO - NOTNLM
OT  - Phase II
OT  - cixutumumab
OT  - pediatric sarcoma
OT  - temsirolimus
COIS- The authors have no conflict of interest to report.
EDAT- 2014/12/03 06:00
MHDA- 2015/03/25 06:00
PMCR- 2016/03/01
CRDT- 2014/12/03 06:00
PHST- 2014/05/30 00:00 [received]
PHST- 2014/10/02 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/03/25 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - 10.1002/pbc.25334 [doi]
PST - ppublish
SO  - Pediatr Blood Cancer. 2015 Mar;62(3):440-4. doi: 10.1002/pbc.25334. Epub 2014 Nov 
      28.