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Adjuvant chemotherapy in resectable liver-limited metastasis colorectal cancer

Adjuvant chemotherapy in resectable liver-limited metastasis colorectal cancer. R4 陳三奇 指導 VS: 鄧豪偉. 財團法人台灣癌症臨床研究發展基金會 . Reference. Clinicopathological features and prognosis in resectable synchronous and metachronous colorectal liver metastasis Ann Surg Oncol 2007

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Adjuvant chemotherapy in resectable liver-limited metastasis colorectal cancer

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  1. Adjuvant chemotherapy in resectable liver-limited metastasis colorectal cancer R4 陳三奇 指導VS: 鄧豪偉 財團法人台灣癌症臨床研究發展基金會

  2. Reference • Clinicopathological features and prognosis in resectable synchronous and metachronous colorectal liver metastasis Ann SurgOncol 2007 • Multicenter Randomized Trial of Adjuvant Fluorouracil and Folinic Acid Compared With Surgery Alone After Resection of Colorectal Liver metastases: FFCD ACHBTH AURC 9002 Trial 2006 JCO • Outcome After Hepatectomy for Multiple (Four or More) Colorectal Metastases in the Era of Effective Chemotherapy 2007 Annals of Surgical Oncology • Adjuvant Chemotherapy After Potentially Curative Resection of Metastases From Colorectal Cancer: A Pooled Analysis of Two Randomized Trials 2007 Annals of Surgical Oncology 2008 JCO. • Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial 2008 Lancet • A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer2009 Annals of oncology • Adjuvant oxaliplatin- or irinotecan-containing chemotherapy improves overall survival following resection of metachronous colorectal liver metastases 2010 Int J Colorectal Dis • NCCN guidline 2012 version 3.

  3. Introduction • Colorectal cancer when diagnosis • 50%-60%: metastases • 20%-34% synchronous liver metastases • Frequent metachronously following treatment.

  4. Prognosis of liver metastasis : • no treatment : 5-year survival- 0.4%-4%. • Palliative CT( fluorouracil ): 3-year survival -5-10%. • Surgery in selected patients: • remove colorectal liver metastases • cure is possible in this population • 5-y-s : 25-40%.

  5. Poor prognostic factor: • >3 metastases, bilobar distribution, an advanced stage of the primary tumor. • The synchronous group : • indicate a more disseminated disease status • a shorter disease-free survival than metachronous metastasis. • Most treatment failures are due to : • local hepatic recurrences • lung metastases • occur within the first 2 years => may need more aggressive chemotherapy ?! Clinicopathological features and prognosis in resectable synchronous and metachronous colorectal liver metastasis Ann Surg Oncol. 2007 Feb;14(2):786-94

  6. Neoadjuvant or adjuvant chemotherpay • Potential advantages of preoperative CT: • Earlier treatment of micrometastatic disease • Determination of responsiveness to chemotherapy (as a prognostic factor and postoperation treatment) • Disadvantages : • liver steatohepatitis and sinusoidal liver injury (irinotecan- and oxaliplatin-based chemotherapeutic regimens) • missing the “window of opportunity” for resection • achievement of a complete response, thereby making it difficult to identify areas for resection.

  7. Method: • Patients: eligible for complete resection of liver metastasis. (n=171) • Randomisedsugery alone or combine with adjuvant chemotherapy. • Follow up time: 87m. • Chemo-regiment: • Leucovorin 200 mg/m2 bolus then • 5-FU 400mg/m2, QD x 5days, monthly, 6 cycles. Multicenter Randomized Trial of Adjuvant Fluorouracil and Folinic Acid Compared With Surgery Alone After Resection of Colorectal Liver metastases: FFCD ACHBTH AURC 9002 Trial 2006 JCO

  8. DFS: 5-y-s: 33.5% vs 26.7% (P=0.028 ) • OS : 5-y-s: 51% vs 41% , (P=0.13) P=0.13 P=0.028 Overall survival Disease free survival Multicenter Randomized Trial of Adjuvant Fluorouracil and Folinic Acid Compared With Surgery Alone After Resection of Colorectal Liver metastases: FFCD ACHBTH AURC 9002 Trial 2006 JCO

  9. Conclusion: • Adjuvant intravenous systemic chemotherapy (5-FU+ LV) provided a significant disease-free survival. Multicenter Randomized Trial of Adjuvant Fluorouracil and Folinic Acid Compared With Surgery Alone After Resection of Colorectal Liver metastases: FFCD ACHBTH AURC 9002 Trial 2006 JCO

  10. Method: • 98 patients with four or more colorectal hepatic metastases were resected. • Neoadjuvant C/T: 57%. 5-FU+ LV, (irinotecan 48% , oxaliplatin 12%) • Adjuvant: 92%. Outcome After Hepatectomy for Multiple (Four or More) Colorectal Metastases in the Era of Effective Chemotherapy 2007 Annals of Surgical Oncology

  11. Actuarial 5-year survival was 33%. • Long-term survival can be achieved after resection of multiple colorectal metastases; however, because most patients will experience recurrence of disease, effective adjuvant therapy and close follow-up is necessary. Outcome After Hepatectomy for Multiple (Four or More) Colorectal Metastases in the Era of Effective Chemotherapy 2007 Annals of Surgical Oncology

  12. 278 patients(CT:138, S:140), complete resection of liver or lung metastasis. • FFCD- Leucovorin 200 mg/m2 bolus then 5-FU 400mg/m2, QD x 5days, monthly, 6 cycles • ENG trial: Leucovorin 100mg/m2, then 5-FU 370mg/m2, QD x 5days, monthly, 6 cycles Adjuvant Chemotherapy After Potentially Curative Resection of Metastases From Colorectal Cancer: A Pooled Analysis of Two Randomized Trials 2007 Annals of Surgical Oncology 2008 JCO.

  13. Conclusion: marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus–based regimen after complete resection of colorectal cancer metastases Adjuvant Chemotherapy After Potentially Curative Resection of Metastases From Colorectal Cancer: A Pooled Analysis of Two Randomized Trials 2007 Annals of Surgical Oncology 2008 JCO.

  14. 364 patients with resectable liver metastases from colorectal cancer. • Randomised 182 patients in perioperative chemotherapy group, 182 in surgery group. • Regimen: FOLFOX4 6cycles before and after surgery. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial 2008 Lancet

  15. Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial 2008 Lancet

  16. 306 patients, completely resectable liver-limited metastases colorectal cancer. • FA, 400 mg/m2 infused over 2h • 5-FU as a 400 mg/m2 i.v. bolus • 5-FU continuous infusion, 2400 mg/m2 over 46 h. • with or without irinotecan: 180 mg/m2 infusion (FOLFIRI) A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer2009 Annals of oncology

  17. Conclusion: FOLFIRI in the adjuvant treatment of LMCRC showed no significant improvement in DFS compared with LV5FUs. A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer2009 Annals of oncology

  18. Between 2000 and 2007, in Taipei Veterans General Hospital hospitalization. • 52 patients having undertaken resection of metachronous colorectal liver disease with curative intent. • 31 patients: FOLFOX or FOLFIRI x 6-12 cycles • 19 patients: 5-FU/leucovorin (LV)-based chemotherapy. Adjuvant oxaliplatin- or irinotecan-containing chemotherapy improves overall survival following resection of metachronous colorectal liver metastases 2010 Int J Colorectal Dis

  19. Conclusions: Adjuvant FOLFOX/FOLFIRI chemotherapy following resection of metachronous CLMs is demonstrated to have better DFS and OS than 5-FU/LV chemotherapy. Adjuvant oxaliplatin- or irinotecan-containing chemotherapy improves overall survival following resection of metachronous colorectal liver metastases 2010 Int J Colorectal Dis

  20. Ongoing trial • HEPATICA study • two-arm, multicenter, randomized, comparative efficacy and safety study. • Randomized after resection or resection combined with RFA • CT: CAPOX + Bevacizumab or CAPOX alone • Follow up 5yrs • The primary endpoint : disease free survival. • Secondary endpoints are overall survival, safety and quality of life

  21. Arm A (CAPOX+Bevacizumab) consists of • 8 cycles of CAPOX (either all cycles postoperatively or 3 cycles preoperatively followed by 5 cycles postoperatively) • Oxaliplatin: 130 mg/m2, day 1, every 3 weeks • Capecitabine: orally ,1000 mg/m2 twice-daily. Day1-14, every 3 weeks. • bevacizumab at 7.5 mg/kg, maximum of 48 weeks. • Arm B : CAPOX only.

  22. Thanks for your attention~

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