L2: Principles of Chemotherapy - Siver

General idea of diagnosing cancer

1. workup: physical exam, biopsy, imaging tests, lab tests, tumor markets, gene sequencing (NGS)

2. staging: dictate prognosis and treatment selection; use the TNM staging system for solid tumors: tumor (size), node (# of lymph nodes), metastasis

benign vs malignant

1. benign: well diff, slow growth, non-invasive, doesn’t metastasize, rarely fatal

2. malignant: poorly diff (anaplastic), rapid, uncontrolled growth, invades surrounding tissue, metastasizes, fatal wo treatment

cancer nomenclature:

1. benign

2. malignant epithelial

3. malignant connective tissue

1. benign: tissue of origin + oma

2. malignant epithelial: carcinoma

3. malignant connective tissue: sarcoma

oncogene

regulate cellular function, positive effectors of transformation; oncogene overexpression results in immortality

• examples: Erb-B (HER2 Neu), N-myc, K-ras

• overexpression

tumor suppressor genes

regulate and inhib inappropriate cell growth, negative growth regulatros, loss of function promotes carcinogenesis

• examples: p53, BRCA1 and 2, retinoblastoma (RB)

• underexpression

T/F oncogenes and tumor suppressor genes both regulate apoptosis

true

What are tumor markers, where are they detected, and what is their primary detection advantage?

• Definition: Antigens or biochemical substances produced by cancer cells.

• Detection site: Serum, plasma, or other bodily fluids.

• Key advantage: Allows detection of cancer without directly accessing the tumor or examining tumor cells directly.

• General significance: Important for diagnostic and prognostic evaluation.

What are the key clinical utilities and diagnostic limitations of tumor markers?

• Clinical Utility:

  • Narrow down cancer type when the primary origin is unknown.

  • Guide treatment selection for specific cancers.

  • Monitor disease progression or therapeutic response.

• Limitations:

  • Variable sensitivity and specificity; often cannot provide confident detection without supplementary tests.

  • Risk of false-positive elevations in noncancerous conditions.

What is Next Generation Gene Sequencing (NGS)?

1. used for DNA/RNA sequencing to ID tumor/molecular biomarkers of the tumor

2. eval and rec for specific types of cancer

3. maximize diag genome info using limited biopsy tissue

4. barriers incliude cost (reimbursement), aval, and evidence of clinical utility

in situ

abnormal cells are present but have not invaded tissue yet, not normally considered cancerous but may become cancerous

localized

cancer is confined to primary site/tissue; no evidence of spread to other regions

regional

cancer has spread to nearby lymph nodes surrounding tissues near the site of the primary tumor

distant

cancer has spread and invaded other parts of the body

goals of cancer treatment

curative, prolong survival, palliation

modalities: surgery, systemic anticancer agents, radiation

what are the 2 types of therapy for solid malignancies?

1. neoadjuvant: properative; admin b4 surgery and/or radiation to reduce tumor burden, clarify surgical margins and eliminate micrometastases

2. surgery

3. adjuvant: systemic therapy admin after surgery or radiaiton to eradicate micrometastases

What are the 4 types of treatments for liquid malignancies?

1. induction therapy: systemic therapy admin to eradicate cancer cells (complete remission)

2. remission

3. consolidation: intensive therapy prevent recurrence after CR

4. maintenance: lower intensity therapy admin after consolidation to prevent recurrence

What are patient factors influencing tumor cell kill?

performance status, immune function, nutritional status, comorbidities

karnofsky performance status (KPS) vs eastern cooperative group performance status (ECOG)

KPS higher # = better the pt

ECOG higher # = worse off pt

Tumor factors influencing tumor cell kill

1. site/location of tumor

2. size: large has bad vascularization, difficult to penetrate w systemic therapy

3. drug resistance

Key concepts of gompertzian growth

Goldie Coldman Hypothesis

1. mathematical model of genetic resistance of cancer cell to chemotherapy

2. describe possibility of resistant cancer cells at time of pt dx

3. proposes: cancer cells could acquire resistance even b4 drug exposure based on the high mutation rate that is intrinsic to the genetic instability of a tumor

Goldie Coldman Hypothesis to overcome resistance:

1. multiple active agents needed to be given as early in the growth of cancer as possible

2. multiple agents given simultaneously will be more effective than sequential agents

will be on exam: which one has higher dose intensity?

200mg every 21 days

cell cycle non specific agents

kill cells throughout the cell cycle; effective against cells in more than one phase

• extent of cell kill depends on the dose

• bolus dose rather than continuous infusion

cell cycle specific agents

kill cells during a specific phase of the cell cycle; effective against cells at specific phases within the cell cycle

• extent of cell kill is maximized if the drug is given in repeated fractions or via a continuous infusion rather than a single large dose

BSA Equation (memorize!) mostellar method expressed as m²

What is the Calvert Equation?

used for carboplatin dose calculation

• carboplatin dose (mg) = target AUC x (GFR+25)

• target AUC 2-6 mg/mL/min

Cockcroft Gault equation used to estimate GFR to measure CrCl. what is the cap?

cap GFR 125ml/min