Dual Targeting of the EGFR/HER2 Pathway in Combination with Systemic Chemotherapy in Refractory Pancreatic Cancer-The CONKO-008 Phase I Investigation.
lapatinib
refractory pancreatic cancer
targeted therapy
tyrosine kinase
Journal
Journal of clinical medicine
ISSN: 2077-0383
Titre abrégé: J Clin Med
Pays: Switzerland
ID NLM: 101606588
Informations de publication
Date de publication:
21 Aug 2022
21 Aug 2022
Historique:
received:
12
06
2022
revised:
11
08
2022
accepted:
17
08
2022
entrez:
26
8
2022
pubmed:
27
8
2022
medline:
27
8
2022
Statut:
epublish
Résumé
Primary objective of this present trial was to define the maximum tolerable dose of lapatinib in combination with oxaliplatin, 5-fluorouracil, and folinic acid (OFF) in refractory pancreatic cancer. The secondary objective was to assess the safety and efficacy of lapatinib plus OFF. We conducted a phase I trial using an accelerated dose escalation design in patients with refractory pancreatic cancer. Lapatinib was given on days 1 to 42 in combination with folinic acid 200 mg/m In total, eighteen patients were enrolled: dose level 1 (1000 mg) was assigned to seven patients, dose level 2 (1250 mg), five patients; and dose level 3 (1500 mg), six patients. Dose-limiting toxicities were diarrhea and/or neutropenic enterocolitis observed in two of six patients: one diarrhea III°, one diarrhea IV°, as well as neutropenic enterocolitis. The maximum tolerable dose of lapatinib was 1250 mg OD. The combination of lapatinib 1250 mg OD with platinum-containing chemotherapy is safe and feasible in patients with refractory pancreatic cancer and warrants further investigation.
Sections du résumé
BACKGROUND
BACKGROUND
Primary objective of this present trial was to define the maximum tolerable dose of lapatinib in combination with oxaliplatin, 5-fluorouracil, and folinic acid (OFF) in refractory pancreatic cancer. The secondary objective was to assess the safety and efficacy of lapatinib plus OFF.
METHODS
METHODS
We conducted a phase I trial using an accelerated dose escalation design in patients with refractory pancreatic cancer. Lapatinib was given on days 1 to 42 in combination with folinic acid 200 mg/m
RESULTS
RESULTS
In total, eighteen patients were enrolled: dose level 1 (1000 mg) was assigned to seven patients, dose level 2 (1250 mg), five patients; and dose level 3 (1500 mg), six patients. Dose-limiting toxicities were diarrhea and/or neutropenic enterocolitis observed in two of six patients: one diarrhea III°, one diarrhea IV°, as well as neutropenic enterocolitis. The maximum tolerable dose of lapatinib was 1250 mg OD.
CONCLUSIONS
CONCLUSIONS
The combination of lapatinib 1250 mg OD with platinum-containing chemotherapy is safe and feasible in patients with refractory pancreatic cancer and warrants further investigation.
Identifiants
pubmed: 36013144
pii: jcm11164905
doi: 10.3390/jcm11164905
pmc: PMC9409879
pii:
doi:
Types de publication
Journal Article
Langues
eng
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