Chemotherapy and Agents

Question 1

6 Roles of Chemotherapy in Head and Neck Oncology

Answer 1

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

Question 2

3 factors affecting Chemotherapy Success

Answer 2

1) Tumour Burden (# of cells)
2) % cells in chemoresponsive phase
3) # of Cells with chemoresistance

Question 3

Alkylating Agents (3) + MOA (1)

Answer 3

Cyclophosphamide
Chlorambucil
Nitrogen Mustard
Dacarbazine

MOA: crosslink DNA to interfere with replication

Question 4

DNA Binding Agents (5) + MOA (1)

Answer 4

Cisplatinum
Carboplatin
Adriamycin (doxorubicin) - induces DNA breaks
Bleomycin - induces DNA breaks
Mitomycin - inhibits fibroblasts + DNA crosslinker

MOA: covalent DNA intercalation, alter replication

Question 5

7 Side effects of Cisplatin (MONNNAE!!) Like money with platinum

Answer 5

1) Myelosuppression 
2 )Ototoxicity (dose limiting, affects high frequencies, cumulative toxicity)
3) Nephrotoxicity 
4) Peripheral Neurotoxicity 
5) Nausea
6) Anorexia
7) Electrolyte disturbances

Question 6

Cisplatin vs. Carboplatinum.

Differences (3) with carbo?
Similarity (1)?

Answer 6

Difference: Decreased Ototoxicity, Neurotoxicity, Nephrotoxicity (MONNNAE but rather MNAE)

Question 7

Antimetabolites (4 examples and MOA of each)

MOA?

Answer 7

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

Question 8

6 Side effects of Methotrexate? “MIND HM”

Response rate as single agent %?

Answer 8

Myelosuppression
Interstitial pneumonitis
N/V/D
Dermatitis

Hepatic fibrosis
Mucositis

RR = 30%

Question 9

5- Fluoro-uracil Side effects (5) MMCDD

Response rate as single agent %?

Answer 9

Myelosuppression
Mucositis
Cardiotoxicity
Dermatitis
Diarrhea

RR = 13%

Question 10

Vinca Alkaloids (3 examples)?

MOA?

Side effect in Children (1)?

Answer 10

Vincristine
Vinblastine
Vinorelbine

MOA = interfere with mitotic spindle formation (microtubule disruptors)

Side Effect = Vocal cord palsy in kids

Question 11

Taxanes (2 examples)?

MOA?

Side Effects (NAAP)

Answer 11

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

Question 12

Topoisomerase Inhibitors (3 examples)

MOA

Answer 12

Irinotecan, Topotecan, Etoposide

Question 13

Cetuximab MOA

Toxicity (3)

Answer 13

Anti-EGFR monoclonal Ab
- inhibits the EGFR monoclonal Ab by blocking the Ligand Binding site

Toxicity - rash, hypomagnesemia, cardiotoxicity

Question 14

Tyrosine Kinase Inhibitors (3 examples)

Side Effect for each one

Answer 14

Gefitinib (Iressa)
Erlotinib (Tarceva)
Sunitinib (Sutent)
Vandetinib (end stage MTC, acts again VEGF/EGFR)

Side effects:

• Diarrhea
• Acneiform Rash

Question 15

Combined Chemotherapy

Answer 15

• higher response rate
• overal survival not improved
• more toxicity
• Cisplatin + 5FU = gold standard (synergistic effects)

Question 16

What are the two (2) standard Chemo-RT regimen for Cisplatin in OTOHNS?

Which one is used when?

Difference in NPC?

Answer 16

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)

Question 17

Benefits of ChemoRT (6) “CRISP”

Answer 17

1. acts on different cell phases/subsets
2. Recruit cells into radiosensitive phases
3. Inhibit repair of sublethal radiation to cells
4. Tumor shrinkage decreases Interstitial pressure, thus increases drug and O2 delivery
5. Prevents radiation resistance
6. Cell-cell synchronization