PMID- 31924737
OWN - NLM
STAT- MEDLINE
DCOM- 20210122
LR  - 20220224
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 26
IP  - 7
DP  - 2020 Apr 1
TI  - Phase I Study of Trifluridine/Tipiracil Plus Irinotecan and Bevacizumab in 
      Advanced Gastrointestinal Tumors.
PG  - 1555-1562
LID - 10.1158/1078-0432.CCR-19-2743 [doi]
AB  - PURPOSE: This two-part phase Ib trial determined the maximum tolerated dose (MTD) 
      of the combination of trifluridine/tipiracil (FTD/TPI) and irinotecan in patients 
      with advanced gastrointestinal tumors, and evaluated the safety, 
      pharmacokinetics, and antitumor activity of the FTD/TPI, irinotecan, and 
      bevacizumab triplet combination in previously treated metastatic colorectal 
      cancer (mCRC). PATIENTS AND METHODS: Dose escalation (3+3 design) in advanced 
      gastrointestinal tumors was followed by expansion in mCRC. During dose 
      escalation, patients received FTD/TPI (20-35 mg/m(2) twice daily; days 1-5 of a 
      14-day cycle) and irinotecan (120-180 mg/m(2); day 1). During expansion, the MTD 
      of FTD/TPI and irinotecan plus bevacizumab (5 mg/kg; day 1) was administered. 
      RESULTS: Fifty patients (26 across six dose-escalation cohorts and 24 in the 
      expansion phase) were enrolled. Two dose-limiting toxicities (fatigue and 
      neutropenia) were observed in the dose-escalation phase, and MTD was defined as 
      FTD/TPI 25 mg/m(2) twice daily plus irinotecan 180 mg/m(2). In the expansion 
      phase, 83% (20/24) experienced any-cause grade >/=3 adverse events (AEs) with the 
      triplet combination, most frequently neutropenia (42%), leukopenia (25%), and 
      diarrhea (12%). AEs of any-cause led to dosing interruptions, modifications, and 
      discontinuations in 29%, 17%, and 4% of patients, respectively. No 
      treatment-related deaths occurred. Three patients (12%) experienced partial 
      responses and 16 (67%) patients had stable disease lasting >4 months. The median 
      progression-free survival was 7.9 months (95% confidence interval, 5.1-13.4 
      months). CONCLUSIONS: Tolerability and activity observed in this phase I trial 
      support further investigation of the FTD/TPI-irinotecan-bevacizumab combination 
      in previously treated mCRC.
CI  - (c)2020 American Association for Cancer Research.
FAU - Varghese, Anna M
AU  - Varghese AM
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
FAU - Cardin, Dana B
AU  - Cardin DB
AD  - Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
FAU - Hersch, Jonathan
AU  - Hersch J
AUID- ORCID: 0000-0002-0435-061X
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
FAU - Benson, Al B
AU  - Benson AB
AD  - Northwestern Medicine, Chicago, Illinois.
FAU - Hochster, Howard S
AU  - Hochster HS
AUID- ORCID: 0000-0002-9893-1529
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
FAU - Makris, Lukas
AU  - Makris L
AD  - Stathmi, Inc., New Hope, Pennsylvania.
FAU - Hamada, Kensuke
AU  - Hamada K
AD  - Taiho Oncology, Inc., Princeton, New Jersey.
FAU - Berlin, Jordan D
AU  - Berlin JD
AUID- ORCID: 0000-0001-7571-2385
AD  - Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
FAU - Saltz, Leonard B
AU  - Saltz LB
AUID- ORCID: 0000-0001-8353-4670
AD  - Memorial Sloan Kettering Cancer Center, New York, New York. saltzl@mskcc.org.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20200110
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Drug Combinations)
RN  - 0 (Pyrrolidines)
RN  - 0 (trifluridine tipiracil drug combination)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - 7673326042 (Irinotecan)
RN  - QR26YLT7LT (Thymine)
RN  - RMW9V5RW38 (Trifluridine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacokinetics/*therapeutic use
MH  - Bevacizumab/administration & dosage
MH  - Drug Combinations
MH  - Female
MH  - Gastrointestinal Neoplasms/*drug therapy/pathology
MH  - Humans
MH  - Irinotecan/administration & dosage
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Patient Safety
MH  - Progression-Free Survival
MH  - Pyrrolidines/administration & dosage
MH  - Thymine/administration & dosage
MH  - Tissue Distribution
MH  - Treatment Outcome
MH  - Trifluridine/administration & dosage
EDAT- 2020/01/12 06:00
MHDA- 2021/01/23 06:00
CRDT- 2020/01/12 06:00
PHST- 2019/10/03 00:00 [received]
PHST- 2019/11/22 00:00 [revised]
PHST- 2020/01/07 00:00 [accepted]
PHST- 2020/01/12 06:00 [pubmed]
PHST- 2021/01/23 06:00 [medline]
PHST- 2020/01/12 06:00 [entrez]
AID - 1078-0432.CCR-19-2743 [pii]
AID - 10.1158/1078-0432.CCR-19-2743 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2020 Apr 1;26(7):1555-1562. doi: 10.1158/1078-0432.CCR-19-2743. 
      Epub 2020 Jan 10.