First-Line Systemic Chemotherapy with Folfoxiri Followed by Radical Surgical Resection of Metastases for the Treatment of Unresectable Metastatic Colorectal Cancer Patients

Abstract

Prognosis of patients with initially unresectable metastatic colorectal cancer (MCRC) can be improved if chemotherapy induces a significant down-sizing of metastatic disease thus allowing a radical (R0) surgical resection of metastases (mts). Moreover, it has been demonstrated that there is a clear correlation between the activity of the regimen used and the rate of secondary R0 resections.We studied the triple drug combination FOLFOXIRI (irinotecan 165 mg/m2 on day 1, oxaliplatin 85 mg/m2 on day 1, 1-leucovorin 200 mg/m2 on day 1, 5-fluorouracil 3,200 mg/m2 48-h flat continuous infusion starting on day 1, repeated every 2 weeks) in phase II and III trials. Overall 196 patients with initially unresectable MCRC not selected for a neoadjuvant strategy were treated. This regimen was associated with a good activity (response rate ranging from 60 to 72%) and 37 patients (19%) underwent to a secondary R0 surgery on metastases after chemotherapy.Characteristics of the 37 radically resected patients were: median age 64 years (45-73), ECOG PS ≥ 1 in 11 patients (30%), median CEA 10 ng/ml (1–288), liver involvement ≥25% in 18 patients (49%). Sites of disease were: liver only 25 patients (68%), lung only 4 patients (11%), liver + lymphnodes 5 patients (13%), liver + peritoneum 1 patient (3%), liver + lung 2 patients (5%). Mts were synchronous in 24 patients (65%) and metachronous in 13 patients (35%). There was no perioperative mortality. After a median follow up of 61 months, median OS is 40.8 months. The actuarial 5-year survival from the onset of chemotherapy is 45%. In 11 patients who showed progression of disease after surgery, a surgical re-resection and/or radiofrequency ablation was performed.These data indicate that FOLFOXIRI allows an R0 surgical resection in about 1 out of 5 patients with initially unresectable MCRC not selected for a neoadjuvant approach. Long term survival of resected patients is significant and comparable with the survival of patients resectable up-front. This FOLFOXIRI regimen should be considered as neoadjuvant treatment in initially unresectable metastatic colorectal cancer patients.KeywordsMetastatic colorectal cancerNeoadjuvant chemotherapyFOLFOXIRISurgical resection of metastases