title: Panitumumab in combination with infusional oxaliplatin and oral capecitabine for conversion therapy in patients with colon cancer and advanced liver metastases. The MetaPan study.
abstract: BACKGROUND
  Preoperative chemotherapy improves the outcome in patients with colorectal cancer with liver metastases. In the current study, the authors evaluated the activity of a conversion treatment with the combination of capecitabine plus oxaliplatin (XELOX) used in association with panitumumab in patients with unresectable, liver-only, metastatic colon cancer.
  
  
  METHODS
  Chemotherapy-naive patients with unresectable liver metastases from colon cancer with no other metastatic disease sites were enrolled. All patients received upfront therapy with XELOX plus panitumumab (P-XELOX) and were reevaluated for resectability every 4 cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints were overall survival (OS), progression-free survival, the percentage of patients whose disease became radically resectable, and the safety of the P-XELOX combination.
  
  
  RESULTS
  A total of 49 patients were recruited, 35 of whom had wild-type KRAS (wtKRAS) and 14 of whom (who were enrolled before study amendment) had unknown (9 patients) or mutated (5 patients) KRAS mutational status. Forty-six patients were evaluable for response. After conversion P-XELOX therapy, the ORR in the general population was 54%, with 2 complete responses, 23 partial responses, and 14 cases of stable disease. In patients with wtKRAS, the ORR of the patients reached 65% (2 CRs and 19 PRs), which allowed 15 patients with initial unresectable liver metastasis to be reclassified as having resectable disease. Survival analysis demonstrated a median progression-free survival of 8.5 months and a median OS of 21.9 months. Patients who underwent surgery were found to have a significantly better OS when compared with those who did not undergo surgery (P < .001). Overall, toxicities were found to be predictable and manageable, with the most common being cutaneous, gastrointestinal, and neurologic toxicities.
  
  
  CONCLUSIONS
  Conversion P-XELOX therapy yields high response and resectability rates for patients with metastatic colon cancer with extensive liver involvement.
authors.affiliation: Department of Medical Oncology, Piemonte Oncology Foundation, IRCC-Candiolo, Candiolo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Leone
authors.forename: Salvatore
authors.initials: S
authors.lastname: Artale
authors.forename: Donatella
authors.initials: D
authors.lastname: Marino
authors.forename: Celeste
authors.initials: C
authors.lastname: Cagnazzo
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.forename: Carmine
authors.initials: C
authors.lastname: Pinto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fornarini
authors.forename: Marco
authors.initials: M
authors.lastname: Tampellini
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Fabio
authors.forename: Andrea
authors.initials: A
authors.lastname: Sartore-Bianchi
authors.forename: Luciano
authors.initials: L
authors.lastname: De Carlis
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pugliese
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Capussotti
authors.forename: Luisa
authors.initials: L
authors.lastname: Gioeni
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D000077544:Panitumumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D000077544:Panitumumab; D005472:Fluorouracil
keywords: capecitabine plus oxaliplatin (XELOX) chemotherapy; colon cancer; liver metastasis; liver resection; panitumumab