Irinotecan, docetaxel and oxaliplatin combination in metastatic gastric or gastroesophageal junction adenocarcinoma

Abstract

This phase II study was designed to evaluate the activity and safety of a combination of irinotecan, docetaxel and oxaliplatin in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Forty patients with measurable distant metastasis received irinotecan 150 mg m À2 and docetaxel 60 mg m À2 on day 1, and oxaliplatin 85 mg m À2 on day 2. Cycles were repeated every 3 weeks. The primary end point was to demonstrate a 50% improvement in time-to-progression (TTP) over historical controls. All patients were evaluable. Median TTP was 6.5 months (95% confidence interval (CI) 5.6 -7.4), the overall response rate was 50% (95% CI 35 -65%) and the median overall survival was 11.5 months (95% CI 8.7 -14.3). Grade 3/4 neutropaenia occurred in 47.5% of patients. There were four episodes of febrile neutropaenia in three patients. Other non-haematological grade 3 toxicities included diarrhoea in four patients (10%), vomiting in three patients (7.5%) and mucositis in two patients (5%). The irinotecan, docetaxel and oxaliplatin combination chemotherapy is an active and well-tolerated novel regimen for treating metastatic gastric or GEJ adenocarcinoma and deserves further evaluation in randomised trials and in combination with molecular targeting agents.

DNA damage repair and survival outcomes in advanced gastric cancer patients treated with first-line chemotherapy

“…We herein examined the expression pattern of central orchestrators of the DDR response in a relatively large series of advanced GC patients treated with first‐line therapy. Approximately half of these patients received chemotherapy in prospective phase II trials . As activation of the ATM‐Chk2/ATR‐Chk1‐Wee1 cascade may be related to, or enforced by, genetic events altering cell cycle progression and DNA repair efficiency, the mutational status of top‐ranking mutated genes in GC ( TP53 and ARID1A ) was assessed.…”

“…Approximately half of these patients received chemotherapy in prospective phase II trials. [10][11][12][13] As activation of the ATM-Chk2/ ATR-Chk1-Wee1 cascade may be related to, or enforced by, genetic events altering cell cycle progression and DNA repair efficiency, the mutational status of top-ranking mutated genes in GC (TP53 and ARID1A) was assessed. Our results suggest that i) a subset of GC is characterized by a robust DDR activation, ii) activation of the system that signals the presence of DSBs may be detrimental for these patients conferring chemoresistant features, as denoted by uni-and multivariate Cox models for PFS and OS and iii) the clinical relevance of this process may be independent on TP53 status, whereas it seemed affected by protein-damaging ARID1A mutations.…”

Optimizing docetaxel chemotherapy in patients with cancer of the gastric and gastroesophageal junction

“…46 The combination of docetaxel at a dose of 60 mg/m 2 and irinotecan at a dose of 150 mg/m 2 on Day 1, plus oxaliplatin at a dose of 85 mg/m 2 on Day 2, has been evaluated in a phase 2 study in patients with metastatic gastric or gastroesophageal junction cancer. 47 A response rate of 50% was observed in 40 patients, with a median OS of 11.5 months. The most notable toxicity was grade 3 neutropenia, which occurred in 48% of patients and 3 patients had 4 episodes of febrile neutropenia.…”

FOLFIRI as a second-line therapy in patients with docetaxel-pretreated gastric cancer: a historical cohort

“…PFS during first-line chemotherapy was ≥ 6 months in 42 patients (60%), and the chemotherapy-free interval was > 3 months in 38 patients (54%). Among regimens administered in the first-line setting, 25 patients (36%) received docetaxel, oxaliplatin and capecitabine [15], 20 patients (28.5%) received epirubicin, cisplatin and docetaxel [16], 19 patients (27%) were treated with epirubicin, oxaliplatin and docetaxel [17], and 6 patients (8.5%) received cisplatin and docetaxel [18]. …”