Treatment of gastrointestinal cancer. General considerations International guidelines
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1 Treatment of gastrointestinal cancer General considerations International guidelines
2 Therapeutical options Chemotherapy Moleculary targeted therapy Irradiation Immunotherapy Radiological intervention Oncosurgery
3 Chemoterapy Systemic therapy Goal :inhibition of proliferation, induction of apoptosis Condition of succes: To consider the biological specificity of tumor and the pharmacological properties of the drug Use of combinations: depends on target, interaction, toxicological properties, profile of side effects
4 Acting in cell cicle Antimetabolits (S) Vinca-alkaloids (M) Taxans(M) Camptotecine (S) Topoizomerase - inhibitors (G2) Antifolates (S) Acting independently from cell cicle Alkylating agentsplatinumderivates Antibiotics -antracyclin Citotoxic agents
5 Target therapy Tirozin kinase inhibitors, multikinase inhibitors, angiogenesis inhibitors, monoclonal antibodies, gene therapy, vaccines They became part of standard treatment combined with cytostatic/cytotoxic drugs or as monotherapy
6 Unsuccess of treatment Tumor mass In bigger tumor mass the number of proliferating cell is lower than in smaller tumor mass: reason for debulking surgery Multidrug resistance Genetic instability of cell. Some resistent cells are present from the beginning, some become resistent under treatment
7 Importance of staging Neoadjuvant: primary systemic treatment 2-4 cicles, depending on effectiveness In case of chemosensitive tumors the planned adjuvant treatment primary Adjuvant: after surgery Goal: to destroy possible micrometastasis Palliativ: evidence of metastasis Untill progression, or serious side effects Stop and go for stable disease
8 Gastrointestinalis tumors High incidence
9 Gastric cancer Diagnosed in advanced phase 20-30%: resectable Controversy in perioperative treatment Neoadjuvant Adjuvant Metastasis: Haematological spred : liver, bone Local infiltration : peritoneum Lymphatic progression: Virchow nodule
10 Treatment strategy
11 Drugs used for treatment Platinum based ( cis-platin, carboplatin ) Fluoropirimidin based( 5- Fluorouracil, capecitabine ) Antracyclin Targeted treatment: Her2neu +++ : trastuzumab only for metastatic disease anti-vegfr 2 antibody ( ramucirumab, apatinib, bevacizumab) under study Irradiation Positive lymphe node status R1 resection
12 Treatment options for different pathologic type Adenocarcinoma: chemotherapy GIST ( gastro-intestinalis stromalis tumor) Imatinib: tirozinkinase inhibitors (Glivec) Lymphoma ( MALT, Hodgkin)
13 Small intestin Treatment: surgery if possible Histology: neuroendocrin tumor or GIST more often Adenocarcinoma is rare
14 Therapeutic options Irradiation Limited because of surrounding organs Recommended for lymphoma Adenocarcinoma chemotherapy: less effective than in colorectal cc questionable Neuroendocrin tumor:depending on grade GIST The mutation of KIT gene : influences the therapeutic response Imatinib, sunitinib ( Glivec, Sutent)
15 Rectum carcinoma Radiotherapy has an important role Regarding quality of life the preservetive surgery an important goal The drugs used for treatment are the same as in colon cancer A different entity: canalis analis
16 Tumors other than adenocarcinoma in rectum Canalis analis tumor Early symmptoms, better prognosis, distant metastasis uncommon. Organ saving procedure must be considered In prevention antiviral treatment has a role (HPV and HIV) Melanoma
17 Role of radiotherapy in treatment of rectal carcinoma Preoperativ/ neoadjuvant Based on CT, MRI images Goal: down staging, local control Low rectal or mid rectal tumors ( till 12 cm) Postoperativ After surgery : resectio is R1,or Palliativ Recidiv tumors, symptoms due to compression
18 Treatment of colon cancer High incidency New therapeutic options available Changes in surgical methods, decisions Number of targeted therapy growing Can be turned in chronic disease
19 Treatment strategy in adjuvant setting Same cytotoxic drugs as in metastatic disease Stage has in important role Targeted treatment showes no advantage Genetic profile can be used as prognostic information
20 Adjuvant treatment of colon Depending on stage Node positiv cancer Node negativ( Dukes B): additional information needed T1NO ( Stage I) no evidence for benefit( Dukes A, DukesB1 Drugs Fluoropirimidin based combination Oxaliplatin combination in node positiv cases Prognostic factors to be considereddihidropirimidindehidrogenáz DPD, MMR, MSI ( MSS)
21 Treatment strategy in metastatic colon cc
22 Treatment strategy in metastatic colon cc
23 Treatment strategy in metastatic colon cc
24 Future Personalized medicine Multigene test Tumorvaccines Immunotherapy in colorectal carcinoma ( MSS in 95% in metastasis )
25 The cause of failure of PD1 inhibitors
26 New drugs under study CEA-TCB (CEA D3 TCB), a novel T-cell bispecific antibody targeting solid tumours CEA expression needed for activity Atezolizumab ( PD1 inhibitor) + cobimetinib( MEK inhibitor) Encouraging clinical activity in metastatic colorectal cancer after failure of at least two prior chemotherapy regimens
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