PMID- 24684785
OWN - NLM
STAT- MEDLINE
DCOM- 20150206
LR  - 20240507
IS  - 1465-542X (Electronic)
IS  - 1465-5411 (Print)
IS  - 1465-5411 (Linking)
VI  - 16
IP  - 2
DP  - 2014 Mar 31
TI  - Phase 2 trial of everolimus and carboplatin combination in patients with triple 
      negative metastatic breast cancer.
PG  - R32
LID - 10.1186/bcr3634 [doi]
AB  - INTRODUCTION: Rapamycin acts synergistically with platinum agents to induce 
      apoptosis and inhibit proliferation in breast cancer cell lines. Combination of 
      everolimus also known as RAD001 (oral mammalian target of rapamycin (mTOR) 
      inhibitor) and carboplatin may have activity in metastatic triple-negative breast 
      cancer (TNBC). METHODS: The primary objective of this study was to determine 
      clinical benefit rate (CBR), that is (complete remission (CR) + partial remission 
      (PR) + stable disease (SD) lasting >/=6 months) and the toxicity of 
      everolimus/carboplatin in women with metastatic TNBC. Prior carboplatin was 
      allowed. Treatment consisted of intravenous carboplatin area under the curve 
      (AUC) 6 (later decreased to AUC 5 and subsequently to AUC 4) every 3 weeks with 
      daily 5 mg everolimus. RESULTS: We enrolled 25 patients in this study. Median age 
      was 58 years. There were one CR, six PRs, seven SDs and eight PDs (progression of 
      disease). CBR was 36% (95% confidence interval (CI) 21.1 to 57.4%). One SD was 
      achieved in a patient progressing on single agent carboplatin. The median 
      progression free survival (PFS) was 3 months (95% CI 1.6 to 4.6 months) and 
      overall survival (OS) was 16.6 months (95% CI 7.3 months to not reached). There 
      were seven patients (28%) with >/= grade 3 thrombocytopenia; three (12%) with grade 
      3 neutropenia (no bleeding/febrile neutropenia) and one (4%) with grade 3 anemia. 
      Greater hematological toxicity was seen in the first seven patients treated with 
      carboplatin AUC5/6. After the amendment for starting dose of carboplatin to AUC 
      4, the regimen was well tolerated with only one out of 18 patients with grade 3 
      neutropenia and two patients with grade 3 thrombocytopenia. There was only one 
      case of mucositis. CONCLUSION: Everolimus-carboplatin was efficacious in 
      metastatic TNBC. Dose limiting hematological toxicity was observed when AUC5/6 of 
      carboplatin was combined with everolimus. However, carboplatin AUC 4 was well 
      tolerated in combination with everolimus with continuing responses. TRIAL 
      REGISTRATIONS: ClinicalTrials.gov NCT01127763.
FAU - Singh, Jasmeet
AU  - Singh J
FAU - Novik, Yelena
AU  - Novik Y
FAU - Stein, Stacey
AU  - Stein S
FAU - Volm, Matthew
AU  - Volm M
FAU - Meyers, Marlene
AU  - Meyers M
FAU - Smith, Julia
AU  - Smith J
FAU - Omene, Coral
AU  - Omene C
FAU - Speyer, James
AU  - Speyer J
FAU - Schneider, Robert
AU  - Schneider R
FAU - Jhaveri, Komal
AU  - Jhaveri K
FAU - Formenti, Silvia
AU  - Formenti S
FAU - Kyriakou, Victoria
AU  - Kyriakou V
FAU - Joseph, Benson
AU  - Joseph B
FAU - Goldberg, Judith D
AU  - Goldberg JD
FAU - Li, Xiaochun
AU  - Li X
FAU - Adams, Sylvia
AU  - Adams S
FAU - Tiersten, Amy
AU  - Tiersten A
LA  - eng
SI  - ClinicalTrials.gov/NCT01127763
GR  - P30 CA016087/CA/NCI NIH HHS/United States
GR  - R01 CA161891/CA/NCI NIH HHS/United States
GR  - P30 CA16087/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140331
PL  - England
TA  - Breast Cancer Res
JT  - Breast cancer research : BCR
JID - 100927353
RN  - 9HW64Q8G6G (Everolimus)
RN  - BG3F62OND5 (Carboplatin)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Anemia/chemically induced
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Carboplatin/administration & dosage/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Everolimus
MH  - Exanthema/chemically induced
MH  - Fatigue/chemically induced
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Middle Aged
MH  - Nausea/chemically induced
MH  - Remission Induction
MH  - Sirolimus/administration & dosage/adverse effects/analogs & derivatives
MH  - Thrombocytopenia/chemically induced
MH  - Treatment Outcome
MH  - Triple Negative Breast Neoplasms/blood/*drug therapy
PMC - PMC4053575
EDAT- 2014/04/02 06:00
MHDA- 2015/02/07 06:00
PMCR- 2014/03/31
CRDT- 2014/04/02 06:00
PHST- 2013/09/09 00:00 [received]
PHST- 2014/03/10 00:00 [accepted]
PHST- 2014/04/02 06:00 [entrez]
PHST- 2014/04/02 06:00 [pubmed]
PHST- 2015/02/07 06:00 [medline]
PHST- 2014/03/31 00:00 [pmc-release]
AID - bcr3634 [pii]
AID - 10.1186/bcr3634 [doi]
PST - epublish
SO  - Breast Cancer Res. 2014 Mar 31;16(2):R32. doi: 10.1186/bcr3634.