PMID- 30889492
OWN - NLM
STAT- In-Data-Review
LR  - 20190430
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 112
DP  - 2019 May
TI  - Phase I dose-escalation of trifluridine/tipiracil in combination with oxaliplatin
      in patients with metastatic colorectal cancer.
PG  - 12-19
LID - S0959-8049(19)30138-8 [pii]
LID - 10.1016/j.ejca.2019.01.101 [doi]
AB  - BACKGROUND AND OBJECTIVES: Pre-clinical data have shown that combining
      trifluridine/tipiracil with oxaliplatin enhances anti-tumour activity compared
      with either monotherapy. A phase I dose-escalation study was conducted to
      determine the maximum tolerated dose (MTD), recommended dose (RD) for phase II
      and pharmacokinetic profile of this combination in patients with metastatic
      colorectal cancer (mCRC) who had progressed after at least 1 prior line of
      treatment. METHODS: Using a 3 + 3 design, patients received escalating
      trifluridine/tipiracil doses from 25, then 30 and to 35 mg/m(2) twice daily, days
      1-5, q14 days, together with a fixed dose of 85 mg/m(2) of oxaliplatin day 1, q14
      days. An intermediate cohort with a lower oxaliplatin dose (65 mg/m(2)) was also 
      investigated. After MTD determination, additional patients were treated to define
      the RD. RESULTS: Twenty-four patients were enrolled. One dose-limiting toxicity
      of grade 3 febrile neutropenia was observed at the highest dose level, which was 
      established as the MTD and subsequently the RD. The most common drug-related
      adverse events (AEs) were asthenia, nausea, diarrhoea, peripheral neuropathy,
      neutropenia, decreased appetite, thrombocytopenia, vomiting, anaemia and
      peripheral sensory neuropathy. Most drug-related AEs (93.0%) were of grade 1-2.
      Pharmacokinetic parameters of trifluridine/tipiracil were not influenced by
      oxaliplatin co-administration. Best overall responses at the RD (n = 14) included
      1 patient with partial response (7.1%) and 7 patients with stable disease
      (50.0%). CONCLUSION: The combination of trifluridine/tipiracil and oxaliplatin in
      patients with mCRC has a manageable safety profile with some efficacy. The RD is 
      35 mg/m(2) of trifluridine/tipiracil twice daily, days 1-5, q14 days and 85
      mg/m(2) of oxaliplatin day 1, q14 CLINICALTRIALS. GOV NUMBER: NCT02848443.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Argiles, Guillem
AU  - Argiles G
AD  - Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat
      Autonoma de Barcelona, Spain. Electronic address: gargiles@vhio.net.
FAU - Andre, Thierry
AU  - Andre T
AD  - Sorbonne Universite et Hopital Saint-Antoine, Service d'Oncologie Medicale, 184, 
      rue du Faubourg-Saint-Antoine, Paris, France.
FAU - Hollebecque, Antoine
AU  - Hollebecque A
AD  - Drug Development Department (DITEP: Departement d'Innovations Therapeutiques et
      Essais Precoces), Gustave Roussy Cancer Campus, Villejuif, France.
FAU - Calvo, Aitana
AU  - Calvo A
AD  - Gregorio Maranon University General Hospital, Madrid, Spain.
FAU - Dahan, Laetitia
AU  - Dahan L
AD  - Aix Marseille University; Assistance Publique Hopitaux de Marseille, Centre
      d'Essais Precoces en Cancerologie de Marseille CLIP(2), Marseille, France.
FAU - Cervantes, Andres
AU  - Cervantes A
AD  - CIBERONC, Department of Medical Oncology, Biomedical Research Institute INCLIVA, 
      University of Valencia, Valencia, Spain.
FAU - Leger, Catherine
AU  - Leger C
AD  - Institut de Recherches Internationales Servier, Suresnes, France.
FAU - Amellal, Nadia
AU  - Amellal N
AD  - Institut de Recherches Internationales Servier, Suresnes, France.
FAU - Fougeray, Ronan
AU  - Fougeray R
AD  - Institut de Recherches Internationales Servier, Suresnes, France.
FAU - Tabernero, Josep
AU  - Tabernero J
AD  - Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat
      Autonoma de Barcelona, Spain.
LA  - eng
SI  - ClinicalTrials.gov/NCT02848443
PT  - Journal Article
DEP - 20190316
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
OTO - NOTNLM
OT  - Fluoropyrimidines
OT  - Metastatic colorectal cancer
OT  - Oxaliplatin
OT  - Trifluridine/tipiracil
EDAT- 2019/03/20 06:00
MHDA- 2019/03/20 06:00
CRDT- 2019/03/20 06:00
PHST- 2018/12/05 00:00 [received]
PHST- 2019/01/18 00:00 [revised]
PHST- 2019/01/25 00:00 [accepted]
PHST- 2019/03/20 06:00 [pubmed]
PHST- 2019/03/20 06:00 [medline]
PHST- 2019/03/20 06:00 [entrez]
AID - S0959-8049(19)30138-8 [pii]
AID - 10.1016/j.ejca.2019.01.101 [doi]
PST - ppublish
SO  - Eur J Cancer. 2019 May;112:12-19. doi: 10.1016/j.ejca.2019.01.101. Epub 2019 Mar 
      16.