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Alfredo Falcone Dipartimento di Oncologia - Azienda USL-6 di Livorno Cattedra di Oncologia Medica - Universit degli Stu

. Liver Metastases in Colorectal Cancer. 60% of CRC pts develop liver mets 25% synchronous 35% methacronous50% of initial recurrences are confined to the liver In 20-30% of advanced CRC pts liver is the only site of mets . . IMPROVEMENTS IN THE TREATMENT OF CRC LIVER METS. More Surgery. SomeB

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Alfredo Falcone Dipartimento di Oncologia - Azienda USL-6 di Livorno Cattedra di Oncologia Medica - Universit degli Stu

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    2. Liver Metastases in Colorectal Cancer 60% of CRC pts develop liver mets 25% synchronous 35% methacronous 50% of initial recurrences are confined to the liver In 20-30% of advanced CRC pts liver is the only site of mets

    4. Improvements in MCRC treatment in the last 10 years

    5. Active treatments available in MCRC

    10. CHEMOTHERAPY (Fluoropyrimidines, Irinotecan, Oxaliplatin)

    12. Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer

    13. Adjuvant 5-FU/LV after resection of liver mets: FFCD ACHBTH AURC 9002 Trial

    15. Chemotherapy in initally unresectable MCRC and liver mets Initial use of a doublet is better than single agent Important to expose patients to 5FU, CPT, LOHP Infusional 5-FU is preferable to bolus Capecitabine can probably be an alternative to 5-FU Reevaluate for surgery responding patients More responses = more resections Initial use of a triplet is better than a doublet in selected patients Chemotherapy-free intervals do not reduce efficacy in selected patients

    16. Trials supporting the use of doublets CPT-11/5FU-LV Saltz, NEJM 2000 (IFL) Douillard, Lancet 2000 (FOLFIRI) Koehne, JCO 2005 (AIO-IRI) LOHP/5FU-LV De Gramont, JCO 2000 (FOLFOX4) Giacchetti, JCO 2000 (Chronoinfusion) Grothey, ASCO 2002 (FUFOX)

    17. Trials supporting equivalent efficacy of doublets containing CPT11 or LOHP with infusional 5FU/LV Tourningard JCO 2004 FOLFIRI vs FOLFOX6 Colucci JCO 2005 FOLFIRI vs FOLFOX4

    19. CORRELATION BETWEEN TUMOR RESPONSE AND RESECTION RATES

    23. FOLFOXIRI SCHEDULE

    31. BEVACIZUMAB AND CETUXIMAB

    39. RESECTABLE PATIENTS In “easily” or “immediately” resectable patients (oncosurge) surgery up-front and consideration for adjuvant CT (5FU-LV, FOLFOX, FUDR) In “not easily” or “marginally” resectable patients and after a multidisciplinary evaluation, an active CT for 2-3 months (doublet or triplet) followed by surgery and further CT

    40. UNRESECTABLE, BUT POTENTIALLY RESECTABLE PATIENTS Systemic CT with a a triplet (FOLFOXIRI) or a doublet (FOLFIRI or FOLFOX) + Bevacizumab reevaluating resectability every 2-3 months Consider studies with an “intensive” approach (Cetuximab+CT, FOLFOXIRI + biologic, etc…)

    41. UNRESECTABLE, BUT NEVER RESECTABLE PATIENTS Fit patients, aggressive disease Systemic CT with a first-line doublet (FOLFIRI or FOLFOX) combined with bevacizumab or a triplet (FOLFOXIRI) and followed after PD by other active agents (FOLFOX or FOLFIRI or Cetuximab+CPT) Unfit patients, less aggressive disease Sequential treatment beginninig with a fluoropyrimidine + bevacizumab (if not controindicated) “Personalized” first-line doublet + bevacizumab followed after PD by other active agents (mainly in pts unfit for advanced tumor) Consider interruption of CT after 2-3 months if SD or response and restart after 2 months break or at progression BSC

    42. CONCLUSIONS Il the lat 10 years we have made substantial progress in the treatment of pts with CRC liver mets. However the chances of long-term survival or cure remain limited Our therapeutic options are increased, treatment has become complex and a multidisciplinary approach is fundamental Need for further improvements through the development of better systemic and local treatments, better selection of pts, better integration

    48. Adjuvant chemotherapy with 5FU/LV after potentially curative resection of mets from CRC. A meta-analysis of two randomized trials

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