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Phase II trial of S-1 plus leucovorin in patients with advanced gastric cancer and clinical prediction by S-1 pharmacogenetic pathway
- Source :
- Cancer Chemotherapy and Pharmacology
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Background The first one-arm phase II trial aimed to evaluate and predict efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach. Patients and methods A total of 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), while the secondary endpoints were progression-free survival (PFS), time to failure (TTF), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Peripheral blood was sampled prospectively for baseline expression of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS), CYP2A6 gene polymorphisms, and 5-FU pharmacokinetics. Results The ORR and DCR were 41.0 and 76.9%. The median PFS, TTF, and OS were 4.13, 3.70, and 11.40 months. Grade 3–4 AEs occurred in only 13 patients, and grade 4 AEs occurred in only 1 of them. High OPRT/TS and peritoneal metastasis (vs. liver metastasis) independently predicted responding. High OPRT/DPD independently predicted grade 3–4 AEs. High AUC0–24h of 5-FU and metastatic/recurrent sites ≤2 (vs. >3) independently predicted prolonged PFS. Low baseline plasmic DPD independently predicted prolonged OS. Conclusions Two-week, oral S-1/LV regimen demonstrated promising efficacy and safety as first-line chemotherapy for AGC. ClinicalTrials.gov identifier NCT02090153
- Subjects :
- Male
0301 basic medicine
Cancer Research
Advanced gastric cancer
medicine.medical_treatment
Leucovorin
Pharmacology
Toxicology
Thymidylate synthase
Gastroenterology
Metastasis
Cytochrome P-450 CYP2A6
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Clinical endpoint
Medicine
Pharmacology (medical)
Aged, 80 and over
biology
Pharmacogenetic
S-1
Middle Aged
Drug Combinations
Oncology
030220 oncology & carcinogenesis
Original Article
Female
Fluorouracil
Adult
medicine.medical_specialty
Orotate Phosphoribosyltransferase
Disease-Free Survival
03 medical and health sciences
Stomach Neoplasms
Internal medicine
Dihydropyrimidine dehydrogenase
Humans
Thymidine phosphorylase
Aged
Tegafur
Chemotherapy
business.industry
medicine.disease
Pharmacogenomic Testing
Oxonic Acid
Regimen
030104 developmental biology
biology.protein
business
Pharmacogenetics
Subjects
Details
- ISSN :
- 14320843 and 03445704
- Volume :
- 79
- Database :
- OpenAIRE
- Journal :
- Cancer Chemotherapy and Pharmacology
- Accession number :
- edsair.doi.dedup.....f13f8d84b2a7df57f15ca76ffef642e4