Treatment for Lung Cancer Flashcards by Stamatia Stratoulia

What are the localised symptoms and signs of lung cancer?

Cough and fatigue
Breathing problems
Blood in phlegm
Chest pain and tightness
Hoarseness & hiccups

How well did you know this?

Not at all

Perfectly

What are the generalised signs and symptoms of lung cancer?

Bone pain
Headaches
Weight loss
Abdominal pain
Hepatomegaly
GI disturbances

How well did you know this?

Not at all

Perfectly

What are the available treatment methods for lung cancer?

Surgery
Radiation
Pharmacotherapy

How well did you know this?

Not at all

Perfectly

What are the two options under pharmacotherapy of lung cancer?

Chemotherapy
Targeted or Biologic therapy

How well did you know this?

Not at all

Perfectly

What are the kinds of drugs given in chemotherapy?

Alkylating agents
Antimetabolites
Topoisomerase inhibitors
Microtubule inhibitors

How well did you know this?

Not at all

Perfectly

What are the examples of alkylating agents?

Cisplatin (1st gen)
Carboplatin (2nd gen)

How well did you know this?

Not at all

Perfectly

What is the mechanism of action of alkylating agents?

Kill tutor cells at all stages of cycle
Form intra-strand and inter-strand crosslinks –> inhibition of DNA synthesis

Bind both to cytoplasmic and nuclear proteins

How well did you know this?

Not at all

Perfectly

Pharmacokinetics of alkylating agents?

Administered via IV

How well did you know this?

Not at all

Perfectly

What is a contraindication of cisplatin?

Aluminium, it reacts and inactivates it

How well did you know this?

Not at all

Perfectly

What are the adverse effects of alkylating agents?

Nephrotoxicity
Ototoxicity
Neurotoxicity
Nausea & Vomiting
Myelosuppression

How well did you know this?

Not at all

Perfectly

What are the examples of antimetabolites (folate antagonists)?

Pemetrexed and Pralatrexate

How well did you know this?

Not at all

Perfectly

What is the mechanism of action for antimetabolites (folate antagonists)?

Inhibits DHFR and enzymes involved in de novo purine nucleotide biosynthesis

Inhibits thymidylate synthase –> lower risk of resistance

How well did you know this?

Not at all

Perfectly

What is the function of the DHFR enzyme?

Converts folic acid into DHF which is then converted into THF

How well did you know this?

Not at all

Perfectly

What is the function of thymidylate synthase?

Converts dUMP into dTMP

How well did you know this?

Not at all

Perfectly

What are the pharmacokinetics of antimetabolites (folate antagonists) ?

Excited in urine
Dose modification is required if renal dysfunction

How well did you know this?

Not at all

Perfectly

What are the adverse effects of antimetabolites (folate antagonists)?

Myelosuppression
Skin rash
Neutropenic sepsis leading to death

How well did you know this?

Not at all

Perfectly

What is an example of antimetabolites (pyrimidine analogs)?

Gemcitabine

How well did you know this?

Not at all

Perfectly

What is the mechanism of action of Gemcitabine?

Gemcitabine diphosphate inhibits ribonuclease reductase required to convert ribonucleotides into deoxyribonucleotides

Gemcitabine triphosphate inhibits DNA polymerase –> blockade of DNA synthesis and repair

How well did you know this?

Not at all

Perfectly

How does Gemcitabine triphosphate go by unrecognised?

It is incorporated into DNA and it is followed by one more normal nucleotide

How well did you know this?

Not at all

Perfectly

What are the adverse effects of Gemcitabine?

Myelosuppression
Hepatic toxicity
Flu-like symptoms !!
GI disturbances
Elevations of serum transaminases
Proteinuria

How well did you know this?

Not at all

Perfectly

What does inhibition of DNA repair by Gemcitabine do to the other agents?

It may increase cytotoxicity

How well did you know this?

Not at all

Perfectly

What are examples of topoisomerase inhibitors?

Irinotecan and Topotecan

How well did you know this?

Not at all

Perfectly

What is Irinotecan?

It is a prodrug that is converted mainly in the liver to a more potent metabolite

How well did you know this?

Not at all

Perfectly

What is Irinotecan converted into?

SN-38 metabolite

How well did you know this?

Not at all

Perfectly

What are the pharmacokinetics of camptothecins?

Irinotecan and SN-38 mainly eliminated in the bile and feces Dose reduction is required in liver dysfunction

Mecanism of action of camptothecins?

Inhibit topoisomerase I --> S phase

What are the adverse effects of camptothecins?

Myelosuppression Diarrhea

What is an example of topoisomerase inhibitor (epipodophylolotoxins)?

Etoposide

What is etoposide?

A semisynthetic derivative of podophyllotoxin

What is the mechanism of action of Etoposide?

Inhibits DNA enzyme topoisomerase II Cell - cycle phase specific and arrests cells in S phase (or early G2)

Pharmacokinetics of Etoposide?

Administered IV or orally Excreted in urine, Dose reduction in patients with renal dysfunction

Adverse effects of Etoposide?

Myelosuppression GI disturbances Alopecia

What is an example of microtubule stabilisers?

Texans

What are examples of taxanes?

Paclitaxel and Docetaxel

Which is more potent: Paclitaxel or Docetaxel?

Docetaxel

What does the original taxmen drug contain?

Cremophor and ethanol --> hypersensitivity reaction and myelosuppression

What does docetaxel contain?

Paclitaxel bound to albumin --> lower incidence of hypersensitivity reactions

Mechanism of action of taxanes?

Stabilise microtubule formation Inhibit angiogenesis

How does resistance develop with taxanes?

Alteration in tubular or tubular binding sites or P-glycoprotein mediated multi drug resistance

Pharmacokinetics of taxanes?

Infused Large distribution --> cannot enter CNS Metabolised by liver Excreted in bile

What are the adverse effects of taxanes?

Myelosuppression Peripheral neuropathy Fluid retention Hypersensitivity reactions

What are the examples of targeted or biologic therapy?

VEGF inhibitors EGFR inhibitors Immunomodulatory monoclonal antibodies ALK inhibitors

What is an example of VEGF inhibitors?

Bevacizumab

What is the mechanism of action of Bevacizumab?

Binds to and inhibits VEGF A --> inhibiting angiogenesis

Pharmacokinetics of Bevacizumab?

IV infusion

What are the adverse effects of Bevacizumab?

Hypertension Bleeding !! Thrombotic Events !! GI perforation Proteinuria

What are examples of the EGFR inhibitors?

Erlotinib and Gefitinib

What is the mechanism of action of EGFR inhibitors?

Inhibition of EGFR kinase

Pharmacokinetics of EGFR inhibitors?

Metabolised by the liver by the CYP3A4 enzyme

What are the adverse effects of EGFR inhibitors?

Skin rash Diarrhea Anorexia Fatigue

What is the difference between Afatinib and the other EGFR inhibitors?

Afatinib irreversibly blocks all kinases of the ErbB family --> binding to kinase domain --> inhibition of tumor growth

What is Osimertinib?

Another EGFR inhibitor which also binds irreversibly

When is OSimertinib used?

1st option for patients who develop resistance to first line therapy (erlotinib and gefitinib)

What are the adverse effects of Osimetinib?

GI toxicities Dermatologic toxicities Pulmonary toxicities

What is Necitumumab?

An EGFR inhibitor which binds to the human EGFR and blocks the binding of EGFR to its ligands

What are the adverse effects of Necitumumab?

Cardiopulmonary arrest Hypomagnesemia Thromboembolytic event Dermatologic toxicities Infusion reactions

What happens if necitumumab is given with pemetrexed and cisplatin?

Higher morbidity

What are the examples of the monoclonal antibodies?

Nivolumab and Pembrolizumab

What is the mechanism of action of nivolumab and pembrolizumab?

PD1 receptor is expressed by activated T cells and serves as checkpoint PD1 ligand is expressed on numerous human tumours Through the interaction, T cell activity becomes limited and tumour evades Nivolumab and pembrolizumab block PD1 from interacting with its receptor --> restoration of T-cell activity

Pharmacokinetics of Pembrolizumab?

Half life of 22 days Very minimal drug interactions

What is a contraindication of Pembrolizumab?

Use of systemic corticosteroids or immunosuppressants should be avoided before the use of drug

pharmacokinetics of Nivolumab?

Half life of 27 days

Adverse effects of Nivolumab?

Headache, URTI, abdominal pain

General adverse effects of monoclonal antibodies?

Immune-mediated toxicities, pneumonitis, colitis and thyroid dysfunction Depending on severity corticosteroids should be started

What is an example of ALK inhibitors?

Crizotinib (1st gen) Alectinib & Ceritinib (2nd gen)

Mechanism of action of Crizotinib?

Binds to the ATP intracellular domain of activated ALK --> inhibiting phosphorylation and downstream signaling

Adverse effects of Crizotinib?

Visual disorders QT prolongation

Mechanism of action of Alectinib and Ceritinib?

Inhibit autophosphorylation of ALK and downward signalling

General adverse effects of Alectinib and Ceritinib?

Fatigue Bradycardia Hepatotoxicity Visual disturbances

Specific adverse effects of Alectinib?

Anemia, constipation, edema and myalgia (alectinib)

Specific adverse effects of Ceritinib?

QT interval prolongation GI toxicity, pancreatitis, hyperglycemia