Chemotherapy and Agents Flashcards
6 Roles of Chemotherapy in Head and Neck Oncology
1) Primary NPC
2) Organ Preservation in Advanced Laryngeal CA
3) Unresectable Disease
4) Recurrent or Metastatic Disease
5) Post operative Adjuvant therapy
6) Investigative/Clinical Trial Therapy
3 factors affecting Chemotherapy Success
1) Tumour Burden (# of cells)
2) % cells in chemoresponsive phase
3) # of Cells with chemoresistance
Alkylating Agents (3) + MOA (1)
Cyclophosphamide
Chlorambucil
Nitrogen Mustard
Dacarbazine
MOA: crosslink DNA to interfere with replication
DNA Binding Agents (5) + MOA (1)
Cisplatinum
Carboplatin
Adriamycin (doxorubicin) - induces DNA breaks
Bleomycin - induces DNA breaks
Mitomycin - inhibits fibroblasts + DNA crosslinker
MOA: covalent DNA intercalation, alter replication
7 Side effects of Cisplatin (MONNNAE!!) Like money with platinum
1) Myelosuppression 2 )Ototoxicity (dose limiting, affects high frequencies, cumulative toxicity) 3) Nephrotoxicity 4) Peripheral Neurotoxicity 5) Nausea 6) Anorexia 7) Electrolyte disturbances
Cisplatin vs. Carboplatinum.
Differences (3) with carbo?
Similarity (1)?
Difference: Decreased Ototoxicity, Neurotoxicity, Nephrotoxicity (MONNNAE but rather MNAE)
Antimetabolites (4 examples and MOA of each)
MOA?
1) Methotrexate – Interferes with Folate Metabolism, inhibits Dihydrofolate Reductase enzyme, interrupts DNA synthesis in S phase
2) 5-FluoroUracil – S phase Uracil Analogue,
A) Incorporated into DNA and halts replication
B) Thymidilate Synthase inhibitor (blocks Thymidine
synthesis) - MAIN FUNCTION
3) Hydroxyurea,
4) Gemcitabine
GENERAL MOA:
Actively interfere with Cellular Metabolism, act in S-phase
6 Side effects of Methotrexate? “MIND HM”
Response rate as single agent %?
Myelosuppression
Interstitial pneumonitis
N/V/D
Dermatitis
Hepatic fibrosis
Mucositis
RR = 30%
5- Fluoro-uracil Side effects (5) MMCDD
Response rate as single agent %?
Myelosuppression Mucositis Cardiotoxicity Dermatitis Diarrhea
RR = 13%
Vinca Alkaloids (3 examples)?
MOA?
Side effect in Children (1)?
Vincristine
Vinblastine
Vinorelbine
MOA = interfere with mitotic spindle formation (microtubule disruptors)
Side Effect = Vocal cord palsy in kids
Taxanes (2 examples)?
MOA?
Side Effects (NAAP)
Paclitaxil
Docitaxil
MOA: cell cycle arrest in G2 by stabilizing microtubules (prevent mitosis)
Side Effects =
1) Neuropathy
2) Alopecia
3) Allergic Reactions
4) Muscular Pain
Topoisomerase Inhibitors (3 examples)
MOA
Irinotecan, Topotecan, Etoposide
Cetuximab MOA
Toxicity (3)
Anti-EGFR monoclonal Ab
- inhibits the EGFR monoclonal Ab by blocking the Ligand Binding site
Toxicity - rash, hypomagnesemia, cardiotoxicity
Tyrosine Kinase Inhibitors (3 examples)
Side Effect for each one
Gefitinib (Iressa)
Erlotinib (Tarceva)
Sunitinib (Sutent)
Vandetinib (end stage MTC, acts again VEGF/EGFR)
Side effects:
- Diarrhea
- Acneiform Rash
Combined Chemotherapy
- higher response rate
- overal survival not improved
- more toxicity
- Cisplatin + 5FU = gold standard (synergistic effects)
What are the two (2) standard Chemo-RT regimen for Cisplatin in OTOHNS?
Which one is used when?
Difference in NPC?
Cisplatin dosing regimens
For high performance status = 100mg/m2 on Day 1, 22, 43
For low performance status = 40mg/m2 qweekly (lower survival outcomes)
In NPC:
- ChemoRT followed by adjuvant chemotherapy (unsure of benefit)
Benefits of ChemoRT (6) “CRISP”
- acts on different cell phases/subsets
- Recruit cells into radiosensitive phases
- Inhibit repair of sublethal radiation to cells
- Tumor shrinkage decreases Interstitial pressure, thus increases drug and O2 delivery
- Prevents radiation resistance
- Cell-cell synchronization
