Docetaxel, oxaliplatin, and capecitabine combination chemotherapy for metastatic gastric cancer

Abstract

Background The incorporation of docetaxel into the cisplatin and fluorouracil backbone has been demonstrated to be an active combination in metastatic gastric cancer. Nevertheless, this regimen is burdened by nonnegligible toxicity. We hypothesized that replacing cisplatin and fluorouracil with oxaliplatin and capecitabine should be an active and safe option for metastatic gastric cancer patients. Methods In this phase II study, we tested the activity of docetaxel in combination with oxaliplatin and capecitabine (DOC) as a first-line treatment. DOC was administered as follows: docetaxel (60 mg/m 2 ) and oxaliplatin (100 mg/ m 2 ) on day 1, and capecitabine (500 mg/m 2 ) was administered orally twice daily given continuously, with cycles repeated every 3 weeks. The primary endpoint was the overall response rate. Results Forty-eight patients entered the study. All patients had metastatic disease (stage IV). None of the patients had previously received chemotherapy for advanced disease. Performance status was 0, 1, and 2 in 25, 58, and 17 % of patients, respectively; 13 patients (27 %) had adenocarcinoma of the gastroesophageal junction, and 29 patients (60.5 %) had two or more metastatic sites. The overall response rate was 52.1 %. Progression-free survival and overall survival were 6.9 and 12.6 months, respectively. The treatment was well tolerated with no treatmentrelated deaths. The most common grade 3-4 toxicity was neutropenia (41 %). Conclusions DOC is an effective and tolerated first-line treatment, and the lower dose of docetaxel and oxaliplatin used in this study compared with other similar regimens does not seem to hamper the antitumor activity.

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.…”

Docetaxel, Oxaliplatin, and 5-Fluorouracil (DOF) in Metastatic and Unresectable Gastric/Gastroesophageal Junction Adenocarcinoma: A Phase II Study with Long-Term Follow-Up

“…Our cohort demonstrated a median OS of 10.3 months. This compares favorably with historical controls of triplet platinum-taxane-fluoropyrimidine regimens [5,[8][9][10][11].…”

“…The median number of cycles was 11 (2-34), with 33 patients (76.7%) receiving 7 or more cycles. Despite 11 patients (25.6%) coming off treatment because of adverse events, the median number of cycles among these patients was eight (range, [5][6][7][8][9][10][11][12][13][14][15][16][17][18], with cumulative sensory neuropathy as the most common toxicity leading to discontinuation. These results compare favorably with other modified triplet regimens that have been subsequently published, such as modified DCF, docetaxel with 5-FU and carboplatin, epirubicin with oxaliplatin and 5-FU, and TEF (docetaxel, oxaliplatin, and 5-FU; Fig.…”

Phase II study of docetaxel, oxaliplatin, and S-1 therapy in patients with metastatic gastric cancer

“…A 3-week DOX regimen consisting of docetaxel at 60 mg/m 2 and oxaliplatin at 100 mg/ m 2 on day 1 and continuous orally administered capecitabine at 1000 mg/m 2 daily yielded an ORR of 52.1 %, a median PFS of 6.9 months, and a median OS of 12.6 months [18]. When docetaxel at 50 mg/m 2 and oxaliplatin at 75 mg/m 2 were administered intravenously on day 1, and capecitabine at 2750 mg/m 2 was administered orally on days 1-7 every 2 weeks, the ORR, median TTP, and median OS were 59 %, 10.0 months, and 18.0 months, respectively [19].…”