Panitumumab in combination with infusional oxaliplatin and oral capecitabine for conversion therapy in patients with colon cancer and advanced liver metastases. The MetaPan study.
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.
['Leone|Francesco|F|', 'Artale|Salvatore|S|', 'Marino|Donatella|D|', 'Cagnazzo|Celeste|C|', 'Cascinu|Stefano|S|', 'Pinto|Carmine|C|', 'Fornarini|Giuseppe|G|', 'Tampellini|Marco|M|', 'Di Fabio|Francesca|F|', 'Sartore-Bianchi|Andrea|A|', 'De Carlis|Luciano|L|', 'Pugliese|Raffaele|R|', 'Capussotti|Lorenzo|L|', 'Gioeni|Luisa|L|', 'Siena|Salvatore|S|', 'Aglietta|Massimo|M|']
D000328:Adult D000368:Aged D000911:Antibodies, Monoclonal D000971:Antineoplastic Combined Chemotherapy Protocols D000069287:Capecitabine D003110:Colonic Neoplasms D003841:Deoxycytidine D018572:Disease-Free Survival D004359:Drug Therapy, Combination D005260:Female D005472:Fluorouracil D006801:Humans D008113:Liver Neoplasms D008297:Male D008875:Middle Aged D009944:Organoplatinum Compounds D000077150:Oxaliplatin D000077544:Panitumumab D016896:Treatment Outcome
panitumumab colon cancer liver metastasis capecitabine plus oxaliplatin (XELOX) chemotherapy liver resection