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.
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Vasile, E. et al. (2009). First-Line Systemic Chemotherapy with Folfoxiri Followed by Radical Surgical Resection of Metastases for the Treatment of Unresectable Metastatic Colorectal Cancer Patients. In: Bonetti, A., Leone, R., Muggia, F.M., Howell, S.B. (eds) Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-459-3_32
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