Systemic Therapy Flashcards

Question

√What is the mechanism of action and examples of topoisomerase inhibitor chemotherapeutic agents? What are the common side effects?

Answer 1

MOA: - Prevent unwinding of DNA for replication by inhibiting topoisomerases I or II Examples: 1. Inhibits I: Irinotecan, Topotecan 2. Inhibits II: Etoposide, Doxorubicin SIDE EFFECTS: 1. Mucositis 2. Dermatitis

Answer 2

Targeted Biologics: - "Mabs" - Cetuximab, Ipilimumab MOA: Monoclonal antibodies against EGFR (epidermal growth factor receptor) SIDE EFFECTS: 1. Cardiotoxicity 2. Dermatitis

Answer 3

aka. Erbitux MOA: - Anti-EGFR Monoclonal antibody - Inhibits the receptor by blocking the ligand binding site of EGFR (inhibiting growth) Dosage: - 400mg/m^2 week 1, then 250mg/m^2 weeks 2-7 Benefits: - Potentiates RT - improves locoregional control Indications: - Used if performance status, age, comorbid conditions precludes platinum based treatments - However recent studies still show no benefit for age > 65 (Bonner trial) Side effects: - Cardiotoxicity (pericarditis, ischemic heart disease) - Acneiform Rash - treated with tetracyclines or clindamycin - Hypomagnesemia - No neuro/oto/nephrotoxicity as much

Answer 4

2014 Petrelli Systematic review - Found cisplatin was better - 12% better absolute overall survival - Suggests that MAC-NC finding of 6.5% was an underestimate (although Cetuximab was not included in that study)

Answer 5

- Compared RT vs. Concurrent RT + Cetuximab in stage III/IV oropharyngeal hypopharyngeal, and laryngeal carcinoma - Results: 10% improvement in survival rate in 5 years - Although this study did not compare directly Cisplatin, this is why Cetuximab is used in patients who are not candidates or cannot tolerate cisplatin - Found the main side effects of Cetuximab are hypersensitivity and acneiform rash - future studies has not proven that the rash predicts response Western update: apparently misled field, later apparently Cetuximab showed no benefit; Bonner trial says “no toxicity” but actually it’s quite terrible.

Answer 6

Tyrosine kinase is involved in the mediation of immune cascades (inhibits EGF/VEGF) - Epidermal growth factor / Vascular endothelial growth factor (VEGF) 1. Gefitinib, Erlotinib, Vandetinib - anti-VEGF/EGFR (used in end stage Medullary thyroid cancer) 2. Imatinib - DFSP (Dermatofibrosarcoma protuberans) and melanoma 3. Diarrhea and acneiform rash (in 50%) which is predictive of better response rate and progression-free survival (not proven!)

Answer 7

Systemic Therapy - Overarching term for all therapies given systemically that's not radiation Chemotherapy - Drugs that interfere with cell cycle and DNA synthesis / inhibiting progression of cell cycle Immunotherapy - Anything that causes BOOSTING of the immune system (allow the immune system to work MORE) Targeted therapy - Targeting a specific receptor or ligand, enzyme, etc. to elicit a function. Example of this is Cetuximab. Even though it's a monoclonal antibody, its function is to target anti-EGFR so it's a targeted therapy. Anti-PD/PDL-1 inhibitors is a monoclonal antibody, but it's function is to boost the immune system

Answer 8

Pathways: - PD-1 and PD-L1 are proteins. - PD-L1 is found on many different cell types and antigen presenting cells, including tumor cells - PD-1 are found on immune cells like T, B, and NK cells - When PD-L1 is bound to PD-1, it prevents the immune cell (E.g. T-cell) from killing other cells (ie. tumor cells). As such, this decreases immune function and leads to cancer growth - Anti-PD-1 / PD-L1 inhibitors are monoclonal antibodies that are immunc checkpoint inhibitors. Essentially, they block PD-1 on the immune cell, or PD-L1 on the tumor cell, effectively preventing the binding of PD-1 with PD-L1. This prevents the decrease in immune function (effectively, "increases" the immune system) thereby making it an option for tumor treatment Anti-PD-1 inhibitors: 1. Pembrolizumab 2. Nivolumab 3. Cemiplimab Anti-PD-L1 inhibitors: 1. Atezolizumab 2. Avelumab 3. Durvalumab

Answer 9

1. Cisplatin/Carboplatin 2. Taxanes 3. 5-FU/Methotrexate 4. Cetuximab

Answer 10

1. Mitosis - Vincristine 2. S phase - 5-Fluorouracil 3. G2 phase - Bleomycin

Answer 11

NP is one location in H/N where concurrent chemoRT followed by adjuvant chemo is used in some centres The benefit of this strategy is at present uncertain (negative studies) and toxicity is substantial

Answer 12

- No change in overall survival - More side effects - Higher response rates are seen with SOME combinations (e.g. Cis+5FU, Carbo-Taxil) - Carbo-5FU used sometimes instead of cisplatin, when cisplatin is contraindicated due to renal failure

Answer 13

- No change in overall survival - Some studies suggest concurrent is better, but can do either (centre-specific) - CANNOT do BOTH induction and concurrent (too toxic for anyone to handle) - rare exception is nasopharyngeal cancer - Best induction combination: Docitaxel-5FU-Cisplatin