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

Cancer Chemother Pharmacol. 2011 Jun;67(6):1435-43. doi: 10.1007/s00280-010-1444-4. Epub 2010 Sep 2.

Abstract

Background: 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.

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

Results: 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/m(2) of capecitabine was initially recommended with 60 mg/m(2) docetaxel and 60 mg/m(2) cisplatin. However, frequent dose modifications at this dose level resulted in a final optimal dose of 937.5 mg/m(2) 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Capecitabine
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Docetaxel
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Taxoids / administration & dosage
  • Young Adult

Substances

  • Taxoids
  • Deoxycytidine
  • Docetaxel
  • Capecitabine
  • Cisplatin
  • Fluorouracil