Oncology Flashcards
Vemurafenib
MOA
Indication
AE
Protein kinase inhibitor
Unresecatble stage IIIC or IV BRAF V600+ve metastatic melanoma
Arthralgia, rash, photosensitivity, fatigue, GI upset, alopecia, palmar-plantar erythrodysaesthesia
Pembro
MOA
Indication
AE
Anti-PD1 antibody
Advanced melanoma
What is the most common side effect of Erlotinib?
Rash
- resembles acne and primarily involves face and neck
MOA of erlotinib?
inhibits tyrosine kinase associated with epidermal growth factor receptors therefore reducing angiogenesis and tumour progression
Erlotinib
Indications?
NSCLCa.
- 1st line in Stage IIIB or Stage IV (mets) with activating EGFR mutations
- maintenance therapy in pts with locally advanced or metastatic NSCLC who have not progressed on 1st line chemotherapy
- patients with locally advanced or metastatic NSCLC who have previously received chemo
Pancreatic cancer
- used in combination with gemcitabine
indicated in locally advanced, unresectable or metsatic pancreatic ca
what is the most emetogenic chemotherapy agent?
> 90%
- Cisplatin
Cyclophosphamide > 1500 mg/m2
Least emetogenic
List vesicant cytotoxic drugs commonly used
Cisplatin Rubicins Mechlorethamine Mitomycin C Mitoxantrone Oxaliplatin Paclitaxel Vinblastine Vincrisitine Vinorelbine
BRAF mutation MOA?
BRAF mutation consist of a substitution of glutamic acid for valine at amino acid 600 (V600E) which leads to constititive activation of downstream signalling in the MAP kinase pathway
List the BRAF inhibitors
Vemurafenib
Dabrafenib
Staging and Tx of NSC lung cancer?
Staging:
Stage I:
- no nodes
Tx- Sx resection +Adj CTx
Stage II:
Nodes on ipsilateral side
Peribronchial and hilar LN
Tx - Sx resection +Adj CTx
Stage III:
nodal disease to mediastinum/subcarinal LN, supraclavicular.
Tumor with invasion of structures above + N2 nodes.
IIIa: ipisliateral
Tx- neoadjuvant CTx followed by Sx or CTx
IIIb: contralateral
Tx: CTx or palliative RTx
Stage IV
distant mets which include
- contralateral lung nodules
- PLEURAL nodules
- MALIGNANT PLEURAL OR PERICARDIAL EFFUSION
Tx:
Palliative RTx
However systemic Tx should be offered to all pts with ECOG 0-2
- Platinum doublet CTx e.g. cisplatin/gemcit 4-6 cycles. Prolongs OS and improves QOL.
- evidence that addition of bevacizumab to platinum doublet in non-squamous NSCLC results in improved RR, PFR, OS.
What is the recommended duration of therapy for adjuvant hormone therapy in premenopausal breast cancer, ER positive?
10 years (lancet, 2013)
What CTx dugs cause peripheral neuropathy?
Platinum e.g. oxalipaltin
Taxanes
Vincristines
What therapy is recommended for all patients receiving aromatase inh?
Vit D and Ca
When do you commence Denosumbab?
If T score
T/F. Absolute benefits of Aromatise Inh are better than Tamoxifen?
True
What is the Tx for a pt with grade 2 intraductal ca with no associated lymphovascular invasion, sentinel nodes clear, ECOG 0, HER 2 +ve?
AI and Taxane based chemo
Do not use combination of anthracycline and trastuzumab as both are cardiotoxic
Elderly female with bony mets secondary to Stage II breast ca treated with mastectomy, triple -ve. What Tx do you offer?
Palliative RTx and denosumab
Which tumours are chemo resistant?
RCC
GIST
Well diff sarcoma - low chemo responsiveness
What is the medical Tx for RCC?
TKI pazopanib/sunitinib
mTOR-I everloimus, temsirolimus
GIST: What RF Types Mutation Tx
Rare tumour from mesenchymal tissue of GIT
Most common form of sarcoma
Most commonly gastric 50-60% and small intestine 30%
RF: Age Familial Carney's triad (GIST, paragnaglioma, pulmonary chondroma) Type 1 NF
Types:
Spindle cell
Epitheliod
MIxed
Mutation:
Onogene c-kit (CD117) in 75-89% of GIST
PDGFR mutations in 10%
Tx: Localised GIST - Sx Post operative therapy: - Imatinib (c-kit inhibitor). AE: periorbital oedema, fatigue and diarhhoea.
Imatinib delays recurrence but NO overall survival
Advanced disease:
90% response rate to imatinib
Acquired mutations in C-kit or PDGFR are the main cause of imatinib resistance.
Sunitinib 2nd line.
Pt on Imatinib for GIST. Progresses. Next Tx?
Increase dose of Imatinib.
If progresses, sunitinib is 2nd line therapy after high dose imatinib
3rd line therapy: Regorafenib, sorafenib, nilotinib
No indication for Sx
List the tumour that corresponds to the marker:
AFP
Beta-HCG
CA15.3
CA-19.9
CA 125
CEA
AFP - Non seminoma
Beta-HCG
- > 10, 000 mIU/mL = Germ cell tumour (Pure Seminoma)
CA15.3
- metastatic breast cancer
CA-19.9 - pancreatic. Monitor response to Tx, recurrence in resected pancreatic ca.
CA- 125 - ovarian
CEA - Colon cancer
List the common AE for the following biological agents:
Bevacizumab (human monoclonal ab VEGF inh)
Erlotinib (reversibleTKI acting on EGFR)
Temsirolimus (derivative of prodrug sirolimus, mTOR inhibitor)
Sorefenib - TKI (VEGF and PDGRF)
Trastuzumab- (AI- monoclonal ab interferes with HER2 rec)
Bevacizumab - HT, bleeding, proteinuria, impaired wound healing
Erlotinib - Skin rash, diarrhoea
Temsirolimus - stomatitis, rash, hyperglycaemia, hyperlipidaemia, pneumonitis
Sorefenib - fatigue, diarrhoea, hand-foot synd
Trastuzumab - reversible cardiomyopathy
When Tx HCC, what do you consider prior to initiating Sorefnib?
Child Pugh Class
Sorafenib is 1st line Tx in Child Pugh Class A with advanced disease (Stage C, portal invasion)
What is the DNA repair mechanism by which BRCA 1 and 2 proteins act?
Double stranded DNA break repair
Pt is a carrier for BRCA 1 gene mutation with a strong family history of breast ca. What Tx is recommended?
prophylactic bilateral salpingoophrectomy is recommended to reduce the risk of breast and ovarian cancer
Rituximab in addition to standard therapy has been proven to be beneficial over standard therapy alone in the induction phase Tx of Class III -IV lupus Nephritis. T/F
False
In hypercalcaemia, Bisphosphonates increase survival. T/F
False
Zoledronic acid reduces the chance of skeletal related events by 15%. Zoledronic acid has greater reduction than Denosumab. T/F for each.
True
False
Oropharyngeal cancer. Factors associated with improved survival?
HPV associated oropharyngeal cancer have a significantly better prognosis at presentation and after disease recurrence compared with other patients.
Early N stage
Negative surgical margins
p16 positivity (indicates HPV +ve)
Gemcitabine AE?
Dyspnoea, 23% of patients
Small fraction develop severe dyspnoea due to pulmonary toxicities such as interstitial pneumonitis, diffuse alveolar damage, pleural effusions, capillary leak syndrome with noncardiogenic pulmonary odema and others
CT - bilateral ground glass opacities, reticular opacities and thickened septal lines. Centrilobular nodules cans be seen.
What is pulmonary lymphangitis carcinomatosis?
Part of the spectrum of metastatic disease.
Microhaematogenous spread to the periphery of the lung with subsequent lymphatic extension toward the hillier region is responsible for 75% of patients. Usually bilateral.
Remaining cases are due to centrifugal extension from a hillier tumour or from an ipsilateral lung or breast ca. In this case the lymphanggitis spread is unilateral.
Which chemotherapy has the greatest risk for infertility?
Cyclophosphamide - amennorhea and male sterility
Which CTx cases irreversible pulmonary fibrosis?
Bleomycin
Which CTx causes infusion toxicity (hypotension) and delayed neutropenia?
Rituximab
Which CTx causes peripheral neuropathy?
Platinums e.g. oxaliplatin, exacerbated by exposure to cold temperatures
and Taxanes
Vincristine causes dose limiting neuropathy
Bortez and thalidomide also commonly cause peripheral neuropathy
For castrate resistant prostate cancer with bony metastasis, what Tx has been shown to improve overall survival?
Taxanes e.g. docetaxel
Cisplatin is one of the most emetogenic chemotherapy agents. What are its AE?
Neutoxicty
nephrotoxicty
Magnesium wasting
What is the single strongest factor for poor survival in breast ca?
Lymph node involvement
2nd is tumour size of primary
What is crizotinib?
Alk inhibitor
Tx of NSCLCa with alk mutation
What is the Mx for progressive prostate cancer with no mets and life expectancy
Radiation
- less invasive and less likely to cause severe urinary incontinence and errectile dysfunction as with radical prostatectomy
TURP - Hormonal Tx - will not produce relief of LUTs - if pt has CVD, may aggravate
Single agent CTx with docetaxel or cabazitaxel should be reserved for pts with castration recurrent metastatic prostate cancer
What are the poor prognostic factors in breast ca?
65 y - higher co-morbidity
Pathologic factors: Stage IV - 5YS 18% Tumour size, >5 cm 5YS 63% Nodal involvement (axillary nodes) Grade Lymphovascular invasion
Tissue markers:
ER -ve
HER2 over expression - unfavourable prognosis
Aromatase inhibitors e.g. anastrozole, letrozole.
MOA
Most significant AE.
MOA:
Inhibits the enzyme aromatase thereby blocking the conversion of testosterone to oestrodial.
NS inhibitors aromatase and letrazole are reversible.
Steroidal inhibitors e.g. exemestane irreversibly bind the aromatase enzyme
AE:
Osteoporosis and fractures most significant.
Others: Hot flushes mood swings sexual dysfunction CVS Hypercholesterolaemia Arthralgia, joint stiffness, bone pain