PMID- 30655615
OWN - NLM
STAT- MEDLINE
DCOM- 20191112
LR  - 20200309
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 120
IP  - 3
DP  - 2019 Feb
TI  - Phase 1 trial of olaparib and oral cyclophosphamide in BRCA breast cancer, 
      recurrent BRCA ovarian cancer, non-BRCA triple-negative breast cancer, and 
      non-BRCA ovarian cancer.
PG  - 279-285
LID - 10.1038/s41416-018-0349-6 [doi]
AB  - BACKGROUND: We conducted a Phase 1 study to evaluate safety and activity of 
      olaparib tablets and oral cyclophosphamide. METHODS: Patients had metastatic 
      breast cancer (BC) or recurrent high-grade serous ovarian cancer (HGSOC), 
      performance status 0-2, and </=3 lines of prior therapy. Patients were treated 
      using a dose escalation strategy with cohort expansion once maximal tolerated 
      dose (MTD) was determined. Dose level 1 (DL1): olaparib 300 mg bid, 
      cyclophosphamide 50 mg on days 1, 3, and 5, weekly. DL2: olaparib 300 mg bid, 
      cyclophosphamide 50 mg, days 1-5 weekly. RESULTS: Of 32 patients, 23 had HGSOC 
      (germline BRCA mutation [gBRCAm] 70%) and 9 had BC (gBRCAm 67%). Four were 
      treated at DL1 and 28 at DL2, the MTD. Haematological adverse events (AEs) were 
      most common: grade 3/4 AEs: lymphopenia 75%, anaemia 31%, neutropenia 37%, 
      thrombocytopenia 47%. Two permanently discontinued treatment due to 
      haematological AEs. In BC, no objective response was reported. Unconfirmed 
      objective response was 48% and 64% for all HGSOC and gBRCAm subset, respectively. 
      CA125 responses were 70% (all HGSOC) and 92% (gBRCAm). CONCLUSIONS: In HGSOC and 
      BC, olaparib 300 mg bid and cyclophosphamide 50 mg on days 1-5 weekly were 
      tolerable and active, particularly in gBRCAm, and is worthy of further 
      investigation.
FAU - Lee, Chee Khoon
AU  - Lee CK
AD  - St George Hospital, Sydney, NSW, Australia. chee.lee@ctc.usyd.edu.au.
AD  - National Health and Medical Research Council (NHMRC) Clinical Trials Centre, 
      Sydney, NSW, Australia. chee.lee@ctc.usyd.edu.au.
FAU - Scott, Clare
AU  - Scott C
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
AD  - Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
AD  - The Royal Melbourne Hospital, Melbourne, VIC, Australia.
FAU - Lindeman, Geoffrey J
AU  - Lindeman GJ
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
AD  - Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
AD  - The Royal Melbourne Hospital, Melbourne, VIC, Australia.
FAU - Hamilton, Anne
AU  - Hamilton A
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
FAU - Lieschke, Elizabeth
AU  - Lieschke E
AD  - Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
FAU - Gibbs, Emma
AU  - Gibbs E
AD  - National Health and Medical Research Council (NHMRC) Clinical Trials Centre, 
      Sydney, NSW, Australia.
FAU - Asher, Rebecca
AU  - Asher R
AD  - National Health and Medical Research Council (NHMRC) Clinical Trials Centre, 
      Sydney, NSW, Australia.
FAU - Badger, Heath
AU  - Badger H
AD  - Breast Cancer Trials Australia & New Zealand, Newcastle, NSW, Australia.
FAU - Paterson, Robin
AU  - Paterson R
AD  - Breast Cancer Trials Australia & New Zealand, Newcastle, NSW, Australia.
FAU - Macnab, Lauren
AU  - Macnab L
AD  - Breast Cancer Trials Australia & New Zealand, Newcastle, NSW, Australia.
FAU - Kwan, Edmond Michael
AU  - Kwan EM
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
FAU - Francis, Prudence A
AU  - Francis PA
AD  - Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
FAU - Boyle, Frances
AU  - Boyle F
AD  - Breast Cancer Trials Australia & New Zealand, Newcastle, NSW, Australia.
AD  - The Mater Hospital, North Sydney, NSW, Australia.
FAU - Friedlander, Michael
AU  - Friedlander M
AD  - Prince of Wales Hospital, Sydney and Prince of Wales Clinical School, University 
      of New South Wales, Sydney, NSW, Australia.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20190117
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (BRCA1 Protein)
RN  - 0 (BRCA2 Protein)
RN  - 0 (Phthalazines)
RN  - 0 (Piperazines)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - WOH1JD9AR8 (olaparib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects
MH  - BRCA1 Protein/genetics
MH  - BRCA2 Protein/genetics
MH  - Cyclophosphamide/*administration & dosage/adverse effects
MH  - Disease-Free Survival
MH  - Dose-Response Relationship, Drug
MH  - Drug-Related Side Effects and Adverse Reactions/classification/pathology
MH  - Female
MH  - Germ-Line Mutation/genetics
MH  - Humans
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Recurrence, Local/drug therapy/genetics/pathology
MH  - Ovarian Neoplasms/*drug therapy/genetics/pathology
MH  - Phthalazines/*administration & dosage/adverse effects
MH  - Piperazines/*administration & dosage/adverse effects
MH  - Triple Negative Breast Neoplasms/*drug therapy/genetics/pathology
PMC - PMC6353881
COIS- The authors declare no competing interests.
EDAT- 2019/01/19 06:00
MHDA- 2019/11/13 06:00
PMCR- 2020/01/17
CRDT- 2019/01/19 06:00
PHST- 2018/06/28 00:00 [received]
PHST- 2018/11/07 00:00 [accepted]
PHST- 2018/11/01 00:00 [revised]
PHST- 2019/01/19 06:00 [pubmed]
PHST- 2019/11/13 06:00 [medline]
PHST- 2019/01/19 06:00 [entrez]
PHST- 2020/01/17 00:00 [pmc-release]
AID - 10.1038/s41416-018-0349-6 [pii]
AID - 349 [pii]
AID - 10.1038/s41416-018-0349-6 [doi]
PST - ppublish
SO  - Br J Cancer. 2019 Feb;120(3):279-285. doi: 10.1038/s41416-018-0349-6. Epub 2019 
      Jan 17.