Phase I/II study of a combination of docetaxel, capecitabine, and cisplatin (DXP) as first-line chemotherapy in patients with advanced gastric cancer

This study was conducted to determine the optimal dosage of the docetaxel-capecitabine-cisplatin (DXP) regimen and to evaluate its efficacy and safety in patients with advanced gastric cancer.

Patients with advanced gastric or esophagogastric junctional adenocarcinoma received capecitabine (days 1–14) and intravenous docetaxel and cisplatin (day 1) every 3 weeks.

In the phase I study, 15 patients were treated with 4 different dose levels. Asthenia and neutropenic fever were the dose-limiting toxicities. For the phase II study, 1,125 mg/m² of capecitabine was initially recommended with 60 mg/m² docetaxel and 60 mg/m² cisplatin. However, frequent dose modifications at this dose level resulted in a final optimal dose of 937.5 mg/m² capecitabine. Among the 40 patients enrolled in the phase II study, 4 complete and 23 partial responses were observed, presenting objective response rate of 68%. Ten patients achieving good response with complete disappearance of distant metastases underwent surgery, and 4 pathologic complete responses were identified. After the median follow-up of 83.7 months (range, 20.2–86.5) in surviving patients, the median overall survival was 14.4 months and median progression-free survival was 7.6 months. The most frequent grade 3/4 adverse events were neutropenia (62.5%) and asthenia (37.5%). Ten per cent of the patients experienced neutropenic fever, with one case of sepsis-induced death.

DXP displays considerable antitumor activity, and may thus present effective first-line treatment for advanced gastric cancer. Further investigation of the efficacy and safety of this regimen in both first-line and neoadjuvant settings is warranted.