Preoperative Capecitabine, Oxaliplatin, and Irinotecan in Resectable Gastric or Gastroesophageal Junction Cancer: Pathological Response as Primary Endpoint and FDG-PET Predictions

Oncology. 2017;93(5):279-286. doi: 10.1159/000479154. Epub 2017 Sep 8.

Abstract

Objectives: This phase II trial was aimed at assessing the safety and activity of capecitabine, oxaliplatin, and irinotecan (COI regimen) as a preoperative treatment for resectable gastric cancer (GC) or gastroesophageal junction (GEJ) cancer.

Methods: Patients affected by T3-T4/N0-N+/M0 GC/GEJ cancer were treated with the COI regimen for 4 cycles followed by restaging and gastroresection with D2 lymphadenectomy. Four postoperative cycles were scheduled. The primary endpoint was pathological response rate according to Becker et al. [Cancer 2003;98:1521-1530]. The potential role of fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) as a predictive biomarker of pathological tumor response was assessed in a subgroup of 19 evaluable patients.

Results: Between January 2011 and October 2015, a total of 40 patients were enrolled. After the preoperative phase, 36 out of 40 patients (90%) were considered eligible for surgery: 12 patients (30%) achieved a pathological response. The most frequent grade 3/4 adverse events were diarrhea (27%), nausea (25%), and fatigue (17%). Grade 3 neutropenia occurred in 7.5% of patients. A lower standard uptake value at baseline FDG-PET/CT was associated with pathological response.

Conclusion: COI combination is active with a manageable toxicity profile in patients with resectable GC or GEJ cancer. FDG-PET/CT imaging as a surrogate biomarker of pathological response in this setting appears fascinating but should be further investigated.

Keywords: Capecitabine; Combination chemotherapy; FDG-PET/CT; Gastric cancer; Irinotecan; Neoadjuvant chemotherapy; Oxaliplatin; Pathological response; Phase II study.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Capecitabine / administration & dosage
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Esophagogastric Junction / drug effects*
  • Esophagogastric Junction / metabolism
  • Esophagogastric Junction / pathology
  • Female
  • Fluorodeoxyglucose F18 / metabolism
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Positron Emission Tomography Computed Tomography / methods
  • Postoperative Care / methods
  • Preoperative Care / methods
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Organoplatinum Compounds
  • Oxaliplatin
  • Fluorodeoxyglucose F18
  • Capecitabine
  • Irinotecan
  • Camptothecin