Downloaded 51 times
Uploaded byJoão Augusto Ribeiro
Adjuvant therapy for colon adenocarcinoma
1) Adjuvant therapy refers to additional treatment given after primary treatment like surgery to eradicate micrometastasis and reduce the risk of cancer recurrence. 2) For colon adenocarcinoma, common adjuvant therapy options include chemotherapy regimens like FOLFOX and CapeOX. Clinical trials have shown these regimens improve disease-free and overall survival for stage III colon cancer patients. 3) Side effects of adjuvant chemotherapy include nausea, diarrhea, fatigue and neuropathy, though most symptoms improve after treatment completion. Elderly patients may receive less intensive regimens due to higher risk of side effects.
More Related Content
Similar to Adjuvant therapy for colon adenocarcinoma
Adjuvant therapy for colon adenocarcinoma
- 1. ADJUVANT THERAPY FORCOLON ADENOCARCINOMA CU: “ O Doente com Cancro” Professor Doutor JL Passos Coelho 24 April 2018 Helena Carolina Dias 2013231 | João Augusto Ribeiro 2013233
- 2. Treatment that isgiven in addition to the primary treatment in order to erradicate micrometastasis Aims to: • Decrease the risk of disease recurrence • Increase disease-free survival • Increase life expectancy ADJUVANT THERAPY FOR COLON ADENOCARCINOMA ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 3. It depends Adjuvant therapy ADJUVANTTHERAPY FOR COLON ADENOCARCINOMA ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 4. Chemoterapy • 5-FU • Leucorovin •Oxaliplatin • Capecitabine Radiotherapy • T4, positive margins or high relapse risk Therapies Directed to Specific Targets • Metastatic cancer TREATMENT OPTIONS ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 5. Accepted approach: 6th to8th week after surgery For each 4 weeks: ↓14% global survival If delated > 2M, efficacy and survival decreases dramatically After recovery from surgery WHEN TO START ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 6. Recommended therapies: 5-FU/Leucovorin FOLFOX FLOX Capecitabine CapeOX CHEMOTHERAPY REGIMENS ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPYTRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 7. 5-FU –inhibition of thymidilate synthase + disruption of DNA Leucorovin – stabilizes TS + 5-FU metabolite. ADR: diarrhea, náusea/vomting, myelossupression Mechanism of action 5-FLUOROURACIL / LEUCOVORIN ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 8. Mechanism of actionof Oxaliplatin Adducts formation Arrest and Inhibition of mRNA synthesis Immunologic mechanisms – mediated by T-cells and dendritic cells Inhibition of thymidylate synthase Downregulation of dihydropyrimidine dehydrogenase ADR: peripheral neuropathy, diarrhea FOLINIC ACID (LEUCOROVIN) + 5-FU + OXALIPLATIN ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 9. ADR: neurotoxicity, hand-footsyndrome, mucositis, thrombocytopenia Capecitabine 5-FU Hepatic metabolization CAPEOX/XELOX – CAPECITABINE + OXALIPLATIN ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 10. Preferential regimen ofFOLFOX in stage III Stage II Stage III MOSAIC TRIAL ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 11. Disease free survivalfor stage III Overall survival for stage III XELOX vs FOLFOX? No significant diferences were observed in the efficacy of FOLFOX vs. XELOX as adjuvant treatment in high-risk stage II or III CRC patients, but definitive conclusions cannot be drawn because of the small size. XELOXA TRIAL ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 12. QUASAR, 2007 O’ CONNOR, 2011 Controversial trials No preferential regímen in high-risk stage II REGIMEN EVIDENCE FOLFOX / FLOX Category 2 ACapeOX Capecitabine 5-FU / Leucovorin STAGE II ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 13. Tumours from individualsshould be tested for MSI in the following situations: o Colorectal cancer diagnosed in a patient who is <50 years of age. o Presence of synchronous, metachronous colorectal or other Lynch-associated tumours, regardless of age. o Colorectal cancer with the MSI-H histology diagnosed in a patient who is <60 years of age. o Colorectal cancer diagnosed in one or more first- degree relatives with a Lynch-related tumour, with one of the cancers being diagnosed under age 50 years. o Colorectal cancer diagnosed in two or more first- or second-degree relatives with Lynch-related tumours, regardless of age.
- 14. MICROSATELITE INSTABILITY (MSI) MSIsporadic CRCs are characterized by specific clinicopathological features: o Mainly female gender o Older age o Right colon location o Mucinous differentiation o Peritumoural lymphocytic infiltrate and Crohn-like inflammatory reaction o Lower stage ( more common in stage II than III) Better prognosis Present in 15% of all CRC MSI is considered a favourable prognostic factor in early stage CRCs, with longer disease free and overall survival. ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 15. CT reducesthe 5-year risk of cancer recurrence or death by about 30% CT only consensually proven beneficial for stage III Therapy duration – 3 or 6 months. REGIMEN EVIDENCE FOLFOX Category 1 A CapeOX Category 1 A FLOX Category 1 A Capecitabine Category 2 A 5-FU / Leucovorin Category 2 A STAGE III ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 16. SIDE EFFECTS • Nauseaand vomiting • Diarrhea • Mucositis • Fatigue • Alopecia • Febrile neutropenia • Palmar-plantar erythrodysesthesia (hand-foot syndrome) • Death – 0,5 to 1% of cases Most symptoms revert after the end of QT. *Oxaliplatine-related neurotoxicity is more prolonged ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 17. ELDERLY PATIENTS • Donot benefit from oxaliplatin therapy • Higher risk due to higher prevalence of comorbilities • Cardiac insuficiency – 5-FU and capecitabine → vasospasm • Worse renal function – impared metabolism of capecitabine • More vulnerable to myelosupression 1st line: 5-FU / LV >70 years ADJUVANT THERAPY TREATMENT OPTIONS CHEMO THERAPY TRIALS STAGE II STAGE III SIDE EFFECTS ELDERLY
- 18. REFERENCES • https://emedicine.medscape.com/article/277496-treatment#d11, consultedon 15/10/2017 at 15h29 • •https://www.uptodate.com/contents/adjuvant-therapy-for-resected-stage-iii-node-positive-colon-cancer (consulted on 18/10/2017 at 17h) • •http://www.uptodate.com/contents/adjuvant-chemotherapy-for-resected-stage-ii-colon-cancer (consulted on 18/10/2017 at 19h) • •National Comprehensive Cancer Network: Clinical Practice Guidelines in Oncology. Colon Cancer. NCCN 1.2018 • •National Comprehensive Cancer Network: Clinical Practice Guidelines in Oncology. Colon Cancer. NCCN 2.2016 • •Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;0(July) • •Yothers G, O’Connell MJ, Allegra CJ, et al. Oxaliplatinas as adjuvant therapy for colon cancer: updated results of NSABP C-07, including survival and subset analysis. J Clin Oncol 2011;29:3768-3774. • Mlecnik, Bernhard, et al. "Integrative analyses of colorectal cancer show immunoscore is a stronger predictor of patient survival than microsatellite instability." Immunity 44.3 (2016): 698-711. • Kannarkatt, Joseph, et al. "Adjuvant chemotherapy for stage II colon cancer: A clinical dilemma." Journal of oncology practice13.4 (2017): 233-241. • Pectasides, Dimitrios G., et al. "Randomized phase III trial of FOLFOX versus XELOX as adjuvant chemotherapy in patients with early-
- 19. REFERENCES • Rustum, YM.Biochemical rationale for the 5-fluorouracil leucovorin combination and update of clinical experience. Journal of Chemotherapy 2003; 2 Suppl 1:5-11. • •Alcindor, T. Oxaliplatin: a review in the era of molecularly targeted therapy. Current Oncology 2011; 18-25. • •André, T., de Gramont A, Vernerey D, et al. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes acoording to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol 2015;33:4176-4187. • •Haller DG, Tabernero J, Maroun J, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol 2011;29:1465-1471. • •O'Connor ES, et al. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol. 2011 Sep; 29(25):3381-8. • •Gray R, Barnwell J, McConkey C, et al. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet 2007;370:2020-2029. • •O’Connor, E. Adjuvant Chemotherapy for Stage II Colon Cancer With Poor Prognostic Features. J Clin Oncol. 2011 Sep 1;29(25):3381-8. • •Buckowitz, A; Knaebel, H. P.; Benner, A; Bläker, H; Gebert, J; Kienle, P; von Knebel Doeberitz, M; Kloor, M (2005). "Microsatellite instability in colorectal cancer is associated with local lymphocyte infiltration and low frequency of distant
Editor's Notes
- #8 Muitos destes doentes têm que fazer hemogramss antes de cada ciclo, para ir controlando a mielossupressão. Se estiverem muoto baixos, tem de se suspender por uma semana. Leucorovina – esta estabilização rwsulta numa inibição prolongada e mais prenunciada da síntese de DNA.
- #9 Parar a Oxiplatina após 3 meses pode prevenir a neurotoxicidade, Continuar os outros fármacos durante 6 meses. Se o cancro avançar pode-se voltar a iniciar a oxiplatina, se os efeitos adversos já tiverem acabado. Muitos destes doentes têm que fazer hemogramss antes de cada ciclo, para ir controlando a mielossupressão. Se estiverem muoto baixos, tem de se suspender por uma semana. Leucorovina – esta estabilização rwsulta numa inibição prolongada e mais prenunciada da síntese de DNA.
- #11 In the MOSAIC study, the addition of oxaliplatin to 5-FU/LV (FOLFOX schema), demonstrated a significantly increased disease-free survival (DFS) at 3 years, with a reduction in the risk of recurrence of 23% compared with the control arm (LV5FU2). The update at the 6-year follow-up confirmed the benefit in DFS of adjuvant treatment with FOLFOX4, and an advantage was also observed in overall survival (OS), but for stage III patients only.
- #16 The consensus recommends 3 months of adjuvant chemotherapy for patients with low-risk disease, defined as T1-3N1 tumors, which includes approximately 60% of stage III patients. For high-risk patients, defined as patients with T4 or N2 tumors, decisions on use of the shorter course should be based on an individual assessment of tolerability, risk, and choice of regimen.
- #18 No significant diferences were observed in the efficacy of FOLFOX vs. XELOX as adjuvante treatment in high-risk stage II or III CRC patients, but definitive conclusions cannot be drawn because of the small size.