Phase I study of orally administered S-1 in combination with epirubicin and oxaliplatin in patients with advanced solid tumors and chemotherapy-naïve advanced or metastatic esophagogastric cancer

. 2017 Mar ; 20 (2) : 358-367. [epub] 20160602

Jazyk angličtina Země Japonsko Médium print-electronic

Typ dokumentu klinické zkoušky, fáze I, časopisecké články, multicentrická studie

Perzistentní odkaz   https://www.medvik.cz/link/pmid27255289
Odkazy

PubMed 27255289
DOI 10.1007/s10120-016-0618-0
PII: 10.1007/s10120-016-0618-0
Knihovny.cz E-zdroje

BACKGROUND: This phase I study investigated the safety and the maximum tolerated dose (MTD) of the oral fluoropyrimidine S-1 when combined with epirubicin and oxaliplatin (EOS). METHODS: Patients aged ≥18 years with advanced or metastatic solid tumors were enrolled in a 3 + 3 design with S-1 dose escalation (two planned cohorts) performed according to the occurrence of dose-limiting toxicity (DLT). On day 1 of each 21-day cycle, patients received epirubicin 50 mg/m2 followed by oxaliplatin 130 mg/m2 (maximum 8 cycles) and then S-1 [20 mg/m2 (cohort 1) or 25 mg/m2 (cohort 2), twice daily]: first dose, evening of day 1; subsequent administration on days 2-14, twice daily; last dose, morning of day 15 (unlimited number of S-1 cycles). After protocol amendment, enrollment in a third cohort was restricted to patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer. RESULTS: DLT was reported for two of the five patients in cohort 2, defining 20 mg/m2 twice daily as the MTD of S-1 combined with epirubicin and oxaliplatin in heavily pretreated patients. Thirteen patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer were subsequently enrolled and treated at an S-1 dose level of 25 mg/m2 twice daily; no DLTs were reported; median overall survival was 13.1 months. Of the 11 evaluable patients, three (27 %) had partial responses and seven (64 %) had stable disease. The safety profile was in line with expectations. CONCLUSIONS: The promising activity of EOS (S-1 dose level, 25 mg/m2 twice daily) and acceptable safety profile support further clinical development of this combination for the first-line treatment of patients with advanced or metastatic esophagogastric cancer.

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