Background: Preoperative chemotherapy improves outcome in potentially resectable colorectal cancer with liver metastases. We evaluated the activity of a neoadiuvant treatment with capecitabine–oxaliplatin (XELOX) associated with the anti-EGFR antibody Panitumumab in patients with unresectable, liver-only, metastatic colorectal cancer (CRC). Patients and methods: Chemotherapy-naïve patients with unresectable liver metastases of CRC and no other metastatic sites were enrolled. Criteria of unresectability were defined as: more than 3 liver metastases including>50% hepatic involvement and requiring a major hepatectomy with controlateral wedge resection or any metastases requiring a resection that does not preserve two contiguous hepatic segments. Since November 2008 only patients earing wild type KRAS were included. All patients received neoadjuvant XELOX plus panitumumab (P-XELOX) and were reevaluated for resectability every four cycles. Primary endpoint was radiological objective response rate (ORR). Secondary endpoints were overall survival (OS), progression free survival (PFS), percentage of patients whose disease became radically resectable, and safety. Results: Forty-nine patients were recruited, of which 35 were KRAS wild type, and 14 (enrolled before study amendment), were unknown (9 patients) or mutated (5 patients). Forty-six were evaluable for response. Following neoadjuvant P-XELOX, the ORR in the general population was 54%, with 3 CR, 22 PR, 14 SD. In wild type KRAS patients ORR reached 65% (3 CR, 18 PR, 7 SD), and this allowed 15 patients with initial unresectable liver metastasis to be converted to resectability. Survival analysis showed median PFS and OS of 8.5 months and 22.1 months, respectively. Resected patients had significantly better OS if compared to unresected (p = 0.00014). The most common toxicities were cutaneous, gastrointestinal, and neurologic. Conclusion: Neoadjuvant P-XELOX yields high response rates for patients with metastatic CRC and extensive liver involvement, and leads to remarkable conversion to resectability of liver metastasis.
PHASE II TRIAL OF PANITUMUMAB IN COMBINATION WITH OXALIPLATIN AND CAPECITABINE CHEMOTHERAPY AS 1ST LINE THERAPY IN PATIENTS WITH COLORECTAL CANCER AND ADVANCED LIVER METASTASES: THE METAPAN STUDY
LEONE, Francesco;Cagnazzo C;TAMPELLINI, MARCO;AGLIETTA, Massimo
2012-01-01
Abstract
Background: Preoperative chemotherapy improves outcome in potentially resectable colorectal cancer with liver metastases. We evaluated the activity of a neoadiuvant treatment with capecitabine–oxaliplatin (XELOX) associated with the anti-EGFR antibody Panitumumab in patients with unresectable, liver-only, metastatic colorectal cancer (CRC). Patients and methods: Chemotherapy-naïve patients with unresectable liver metastases of CRC and no other metastatic sites were enrolled. Criteria of unresectability were defined as: more than 3 liver metastases including>50% hepatic involvement and requiring a major hepatectomy with controlateral wedge resection or any metastases requiring a resection that does not preserve two contiguous hepatic segments. Since November 2008 only patients earing wild type KRAS were included. All patients received neoadjuvant XELOX plus panitumumab (P-XELOX) and were reevaluated for resectability every four cycles. Primary endpoint was radiological objective response rate (ORR). Secondary endpoints were overall survival (OS), progression free survival (PFS), percentage of patients whose disease became radically resectable, and safety. Results: Forty-nine patients were recruited, of which 35 were KRAS wild type, and 14 (enrolled before study amendment), were unknown (9 patients) or mutated (5 patients). Forty-six were evaluable for response. Following neoadjuvant P-XELOX, the ORR in the general population was 54%, with 3 CR, 22 PR, 14 SD. In wild type KRAS patients ORR reached 65% (3 CR, 18 PR, 7 SD), and this allowed 15 patients with initial unresectable liver metastasis to be converted to resectability. Survival analysis showed median PFS and OS of 8.5 months and 22.1 months, respectively. Resected patients had significantly better OS if compared to unresected (p = 0.00014). The most common toxicities were cutaneous, gastrointestinal, and neurologic. Conclusion: Neoadjuvant P-XELOX yields high response rates for patients with metastatic CRC and extensive liver involvement, and leads to remarkable conversion to resectability of liver metastasis.
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