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: Francesco Leone, Salvatore Artale, Donatella Marino, Celeste Cagnazzo, Stefano Cascinu, Carmine Pinto, Giuseppe Fornarini, Marco Tampellini, Francesca Di Fabio, Andrea Sartore-Bianchi, Luciano De Carlis, Raffaele Pugliese, Lorenzo Capussotti, Luisa Gioeni, Salvatore Siena, Massimo Aglietta
• Journal: Cancer (Cancer) Vol. 119 Issue 19 Pg. 3429-35 (Oct 01 2013) ISSN: 1097-0142 [Electronic] United States
• PMID: 23868516 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American Cancer Society.

Chemical References

• Antibodies, Monoclonal
• Organoplatinum Compounds
• Oxaliplatin
• Deoxycytidine
• Capecitabine
• Panitumumab
• Fluorouracil

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Capecitabine
• Colonic Neoplasms (drug therapy, pathology)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Disease-Free Survival
• Drug Therapy, Combination
• Female
• Fluorouracil (administration & dosage, adverse effects, analogs & derivatives)
• Humans
• Liver Neoplasms (drug therapy, secondary)
• Male
• Middle Aged
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Oxaliplatin
• Panitumumab
• Treatment Outcome