title: Phase I/II trial of capecitabine and oxaliplatin in combination with bevacizumab and imatinib in patients with metastatic colorectal cancer: AIO KRK 0205.
abstract: BACKGROUND
  Combined inhibition of platelet-derived growth factor receptor beta signalling and vascular endothelial growth factor promotes vascular normalisation in preclinical models and may lead to increased delivery of chemotherapy to tumour tissue. This phase I/II trial assessed the safety and efficacy of capecitabine plus oxaliplatin (XELOX) plus bevacizumab and imatinib in the first-line treatment of patients with metastatic colorectal cancer.
  
  
  METHODS
  Two dose levels (I/II) were defined: capecitabine 850/1000 mg m(-2) twice daily on days 1-14; oxaliplatin 100/130 mg m(-2) on day 1; bevacizumab 7.5 mg kg(-1) on day 1; imatinib 300 mg day(-1) on days 1-21 every 21 days. The primary study endpoint was safety. The phase II secondary endpoint was 6-month progression-free survival (PFS).
  
  
  RESULTS
  Dose level I was chosen for phase II testing because, even though further dose escalation was permitted by the protocol, gastrointestinal toxicities were considered to be clinically significant. A total of 49 patients were evaluated. The 6-month PFS rate was 76%, median PFS was 10.6 months and median overall survival was 23.2 months. Haematological toxicities were generally mild. Sensory neuropathy and diarrhoea were the most common grade 3 toxicities.
  
  
  CONCLUSIONS
  The combination of XELOX with bevacizumab and imatinib is tolerable and has promising efficacy.
authors: Department I of Internal Medicine, Prosper Hospital Recklinghausen, 44879 Recklinghausen, Germany.
authors: T
authors: T
authors: Hoehler
authors: G
authors: G
authors: von Wichert
authors: C
authors: C
authors: Schimanski
authors: S
authors: S
authors: Kanzler
authors: M H
authors: MH
authors: Moehler
authors: A
authors: A
authors: Hinke
authors: T
authors: T
authors: Seufferlein
authors: J
authors: J
authors: Siebler
authors: A
authors: A
authors: Hochhaus
authors: D
authors: D
authors: Arnold
authors: M
authors: M
authors: Hallek
authors: R
authors: R
authors: Hofheinz
authors: U T
authors: UT
authors: Hacker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects; D000068258:Bevacizumab; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D001549:Benzamides; D009944:Organoplatinum Compounds; D010879:Piperazines; D011743:Pyrimidines; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000068877:Imatinib Mesylate; D005472:Fluorouracil
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