Lung Cancer Treatment - Clinical Pharmacology II

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Questions and Answers

What is the primary mechanism of action of platinum-based chemotherapy in lung cancer treatment?

Inhibition of DNA synthesis

Blockage of angiogenesis

Enhancement of immune response

Induction of cellular apoptosis (correct)

What is the primary reason for the development of cisplatin resistance in lung cancer treatment?

Decreased drug uptake

Increased DNA repair mechanisms

Enhanced immune response

All of the above (correct)

What is the main adverse effect of oxaliplatin that is more pronounced than with cisplatin?

Myelosuppression

Nephrotoxicity

Severe nausea and vomiting

Cold-induced and cumulative neuropathy (correct)

What is the primary function of the major histocompatibility complex (MHC) in immunology?

Presentation of antigens to T-cell receptors Signup and view all the answers

What is the main mechanism by which cancer cells evade the immune system?

Binding to inhibitory receptors on T-cells Signup and view all the answers

What is the primary adverse effect of immune checkpoint inhibitors (ICIs)?

Autoimmune response to normal tissues Signup and view all the answers

What is the primary mechanism of action of nivolumab in the 'Checkmate 816' trial?

Blockage of PD-1/PD-L1 pathway Signup and view all the answers

What is the primary difference between neoadjuvant and adjuvant therapy?

Timing of therapy in relation to surgery or radiation Signup and view all the answers

What is the primary mechanism of action of 5-HT3 receptor antagonists in managing severe nausea and vomiting?

Blockage of nausea and vomiting signaling pathways Signup and view all the answers

What is the primary reason for the approval of immune checkpoint inhibitors as the standard of care in modern oncology?

All of the above Signup and view all the answers

What is the primary mechanism of action of PD-1/PD-L1 inhibitors in cancer treatment?

Enhancing the cytotoxic effect of CD8 cells on tumor cells Signup and view all the answers

Which of the following is NOT a tyrosine kinase inhibitor?

Ipilimumab Signup and view all the answers

What is the primary target of EGFR tyrosine kinase inhibitors?

EGF-R gene Signup and view all the answers

Which of the following is a contraindication for the use of tyrosine kinase inhibitors?

Absence of gene mutations Signup and view all the answers

What is the response rate of ALK tyrosine kinase inhibitors in patients with ALK gene mutations?

47-83% Signup and view all the answers

What is the role of primary care, urgent care, EM, and IM PAs in cancer treatment decision-making?

Recognizing acute symptoms as potential adverse effects of cancer medications Signup and view all the answers

What is the mechanism of action of CTLA-4 inhibitors in cancer treatment?

Inhibiting the expression of CTLA-4 on T-cells Signup and view all the answers

Which of the following is a characteristic of tyrosine kinase inhibitors?

They are used to treat cancer only in the presence of specific gene mutations Signup and view all the answers

Study Notes

What is Cancer?

Cancer is when cells grow uncontrollably due to genetic alterations.
These alterations affect genes, which are the instruction manual for cell behavior.
Cancerous cells can invade or damage nearby tissues or travel to other locations.

Treatment Strategies

Neoadjuvant therapy: giving drugs before surgery or radiation.
Adjuvant therapy: giving drugs after surgery or radiation.
Combination therapies can include chemotherapy, checkpoint inhibitors, and targeted therapies.

Traditional Treatment of Lung Cancer

Platinum-based chemotherapy: Cisplatin, Carboplatin, and Oxaliplatin.
Platinum moieties bind to DNA, interfering with synthesis, leading to cellular apoptosis.

Cisplatin Resistance

Decreasing drug uptake
Increasing drug efflux
Inducing drug detoxification
DNA repair mechanisms

Adverse Effects of Lung Cancer Treatment

Severe N/V: managed with 5-HT3 receptor antagonists (like ondansetron)
Nephrotoxic: more important with cisplatin, mitigated by aggressive IV hydration
Myelosuppression: more important with carboplatin and oxaliplatin
Neurotoxic: cold-induced and cumulative neuropathy with oxaliplatin
Ototoxic, hypomagnesemia, hypocalcemia, and hypokalemia

Immunology Refresher

MHC on antigen-presenting cells (APCs) presents antigens to T-cell receptor (TCR)
2nd signal often required for T-cell activation, like CD80 from APC to CD28 on T-cell
Activated T-cells bring CTLA-4 and PD-1 to their surface to prevent excessive inflammation

How Cancer Subverts Immunology

Cancer cells can bind to inhibitory receptors on T-cells and deactivate them
Immune checkpoint inhibitors (ICIs) target these receptors to prevent deactivation

Immune Checkpoint Inhibitors

2011: first approval for ICIs
Over 80 FDA-approved uses for over 17 concerns
Considered the standard of care in modern oncology
AE: autoimmune response to normal tissues, treated with corticosteroids

PD-1/PD-L1 Inhibitors

Nivolumab (Opdivo), PD-1
Pembrolizumab (Keytruda), PD-1
Cemiplimab (Libtayo), PD-1
Atezolizumab (Tecentriq), PD-L1
Durvalumab (Imfinzi), PD-L1

CTLA-4 Inhibitors

Ipilimumab (Yervoy)
Tremelimumab (Imjudo)

Tyrosine Kinase Inhibitors

Gene mutations cause abnormal cell behaviors
Tyrosine kinases are involved in cell growth processes
Each has their own adverse effects, monitoring parameters, and contraindications

ALK Tyrosine Kinase Inhibitors

ALK gene codes for anaplastic lymphoma kinase (ALK), involved in cell growth
Mutated forms of ALK gene and protein found in non-small cell lung cancer
ALK TKIs recommended as first-line therapy in patients with ALK gene mutations, with response rates between 47-83%

EGFR Tyrosine Kinase Inhibitors

EGF-R gene codes for Epidermal Growth Factor (EGF) Receptor on cell surface
Mutations in the gene can cause EGF-R upregulation on cancer cells
EGFR TKIs recommended as first-line therapy in patients with EGFR gene mutations, with response rates of at least 70%

Final Thoughts

Decisions on cancer treatments are ultimately not up to primary care, urgent care, EM, or IM PAs
Recognize these drugs and their potential adverse effects, which can be acute symptoms seen in patients

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Description

A quiz on lung malignancy treatment, covering clinical pharmacology concepts, taught by Michael A. Sharma from UT Southwestern Medical Center and Franklin Pierce University.