Chemotherapy

Question 1

In what setting is PACLITAXEL dose reduction mandated?

Answer 1

LIVER DYSFUNCTION

Question 2

Which tumor stains + for ALK (Tyr Kinase)? What chromosomal translocation is associated with this? What other tumor is this very similar to?

Answer 2

ANAPLASTIC LARGE T CELL LYMPHOMA
t(2;5) - NPM-ALK fusion protein
Very similar to Bcr-abl fusion protein of CML [t(9;22)] - Constitutively active Tyr kinase (ALK, abl)

Question 3

Is ALK normally expressed in T lymphocytes? Does ANAPLASTIC LARGE T CELL LYMPHOMA respond well to treatment?

Answer 3

No, not normally expressed
Yes, it responds well specifically to the ALK kinase inhibitor (like IMATINIB that blocks abl Tyr kinase specifically) - 75-80% cure rate

Question 4

Cancer pts who are deficient in which 2 enzymes can develop systemic cytotoxicity to 5-FLUOROURACIL (oral ulcers + photosensitivity)?

Answer 4

1. DPD - DIHYDROPYRIMIDINE DEFICIENCY - Enz that catabolizes the 5-FU -> More buildup of 5-FU
2. THYMIDYLATE SYNTHASE DEFICIENCY - Enz that 5-FU acts on. Less substrate -> More buildup of 5-FU

Question 5

Which chemotherapeutic drug can have the side effect of PERIPHERAL NEUROPATHY?

Answer 5

Any Microtubule inhibitor drug

1. VINCRISTINE/VINBLASTINE - particularly vincristine
2. PACLITAXEL - also binds to MT and promotes stabilization and polymerization of MT -> anaphase can not occur

Question 6

Where are ANTHRACYCLINES (e.g. DOXORUBICIN) derived from? What are the ACUTE toxic effects? What are the CHRONIC toxic effects?

Answer 6

STREPTOMYCES PEUCETIUS soil microbe
ACUTE Effects- Arrhythmia
CHRONIC Effects- Dilated cardiomyopathy

Question 7

What route of administration of VINCRISTINE/VINBLASTINE is absolutely contraindicated?

Answer 7

INTRATHECAL (around the spinal cord) - Immediately results in DEATH because of its toxicity of peripheral neuropathy

Question 8

In what setting (2) is METHOTREXATE dose adjustment required to avoid toxicity?

Answer 8

1. RENAL INSUFFICIENCY - Since MTX is renally excreted
2. ASA, PCN, NSAIDS Co-administration - ASA and NSAIDS inhibit PG -> Modulate renal blood flow -> Precipitates renal toxicity in pts who have marginal renal fn

Question 9

Which chemotherapy drug is anti-ABL (Tyr kinase) in CML?

Answer 9

IMATINIB

Question 10

Which chemotherapy drug is anti-ALK (Tyr kinase) in ANAPLASTIC LARGE T CELL LYMPHOMA?

Answer 10

CRIZOTINIB

Question 11

Which chemotherapy drug is anti-HER2/EGF2/neu in breast cancer?

Answer 11

TRASTUZUMAB

Question 12

Which chemotherapy drug is anti-VEGF?

Answer 12

BEVACIZUMAB

Question 13

Which chemotherapy drug is anti-RAF?

Answer 13

SORAFINIB

Question 14

What are the two mechanisms of developing resistance to IMATINIB for pts with CML?

Answer 14

1. (MORE COMMON) - Point mutation in the KINASE DOMAIN of bcr-abl = ABL protein
2. OVERPRODUCTION of native BCR-ABL resulting in ineffective, limited action of IMATINIB