Feasibility of biweekly combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in patients with metastatic solid tumors: results of a two-step phase I trial: XELIRI and XELIRINOX

Cancer Chemother Pharmacol. 2012 Mar;69(3):807-14. doi: 10.1007/s00280-011-1764-z. Epub 2011 Oct 30.

Abstract

Background: Biweekly schedule of capecitabine combined with irinotecan (XELIRI), consecutively with irinotecan and oxaliplatin (XELIRINOX), was evaluated in patients with metastatic cancer from any solid tumors.

Patients and methods: In this two-step phase I trial, seventeen and eleven patients were enrolled in the XELIRI and XELIRINOX stages, respectively.

Results: In XELIRI, a total of 136 chemotherapy cycles were administered with a median number of 8 cycles per patient (2-16). Main dose-limiting toxicities (DLT) were grade 3-4 neutropenia, with one toxicity-related death. Maximum tolerated dose (MTD) for capecitabine combined with 180 mg/m(2) of irinotecan was 3,500 mg/m(2)/day. In XELIRINOX, capecitabine starting dose was 2,500 mg/m(2)/day. Fifty-eight chemotherapy cycles were administered with a median of 4 cycles per patient (1-16). DLT included 3 grade 4 neutropenia, associated with 1 grade 3 diarrhea, and 1 grade 4 pneumopathy leading to patient death. MTD for capecitabine with 180 mg/m(2) of irinotecan and 85 mg/m(2) of oxaliplatin was 3,000 mg/m(2)/day. The recommended doses for capecitabine were 3,000 and 2,500 mg/m(2)/day D1-D7 in combination with 180 mg/m(2) of irinotecan in XELIRI, plus 85 mg/m(2) of oxaliplatin in XELIRINOX (D1 = D14), respectively.

Conclusion: XELIRI and XELIRINOX regimens are feasible and warrant further investigation in combination with targeted therapy in metastatic colorectal cancer patients.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacokinetics
  • Camptothecin / therapeutic use
  • Capecitabine
  • Chromatography, High Pressure Liquid
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacokinetics
  • Deoxycytidine / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Feasibility Studies
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / analogs & derivatives
  • Fluorouracil / pharmacokinetics
  • Fluorouracil / therapeutic use
  • Glucuronosyltransferase / genetics
  • Humans
  • Irinotecan
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / pharmacokinetics
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Prospective Studies

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Capecitabine
  • Irinotecan
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Fluorouracil
  • Camptothecin