Intracellular poisons 3 Flashcards
What is doxorubicin and what is its major use?
It is a topoisomerase inhibitor (Topo 2)
- it fights against breast cancer and other solid tumors, lymphomas and leukemias
- very broad spectrum anti-cancer
- also generates free radicals
- small molecule
What are some common DLTs of doxorubicin?
Stomatitis and myelosuppression
- after years can cause cardiac damage
- strong vesicant (causes blisters) must be given via central line
What is given in order to mitigate the cardiac toxicity of doxorubicin?
Give Dexrazoane which is an iron chelating agent
what is the lifetime dose of Doxorubicin?
less than 300 mg/m2
typical 5 cycles for breast cancer dose
What is the cardiac toxicity of doxorubicin?
Dilated cardiomyopathy
What is Etoposide?
Topo 2 inhibitor
- small molecule
- broad spectrum anti-cancer
what does Etoposide fight against?
Germ cell tumors
- Agressive lymphomas
- small cell lung cancers
- leukemias
What are the side effects of Etoposide?
Myelosuppresion and alopecia
- can cause acute leukemia in 2-3/1000 at 2-3 yr latency
- these leukemias are usually fatal
What is Paclitaxel?
Anti-tubulin
- small molecule
- broad spec
What is paclitaxel and other taxols used for?
Ovarian and breast carcinomas
- Epithelial malignancies
What are the adverse effects of Paclitaxel and other taxols?
Myelosuppresion, neuropathy and hypersensitivity
-dlt is neuropathy
How does Paclitaxel and other taxols work?
Hyper-stablizes polymerized microtubules in M phase by binding the inner surface of microtubule where GDP binds to the beta subunit
- preventing depolymerization
- cell cannot go to anaphase
What are some other microtubules drugs?
Vincristine (Vinca Alkaloids)
Eribulin
Halichondrin B
What is combined with paclitaxel for regimen for solid tumors?
Carboplatin
How do Vinca alkaloids work?
Bind Beta-tubulin and inhibit polymerization into microtubules preventing mitotic spindle formation
What is the DLT of Vinca alkaloids?
Neuropathy (Long axon transport need microtubules for function)
——– areflexia and peripheral neuritis
Constipation
Are vinca alkaloids myelosuppressive?
NO
How does Eribulin work?
Binds to + end of microtubule preventing elongation
What is the DLT of Eribulin?
Like most anti-microtubules = neuropathy
- myelosuppression is dose limited
- $7,600/month where pac is $100/month
What is Bortezomib?
Proteasome inhibitor
- small molecule
What is Bortezomib most common fight against?
Multiple myeloma
- mantle cell lymphoma
- Waldenstrom’s
- B-cell malignancies
What is the MOA of Bortezomib?
Blocks 26s proteasome proteolytic activity (a threonine protease)
- last 24 hrs after single dose
- IV or subcue
What are the DLT’s of Bortezomib?
Fatigue
Neuropathy
Myelosuppresion
What are the Camptothecins?
Camptothecin
Irinotecan
Topotecan
What is the MOA of Irinotecan?
Topo 1 inhibitor
- its active metabolite SN-38 can be liverated by ubiquitous hydrolytic enzymes either inside or outside clells
- p-450
- turned back to SN-38 by gut flora and SN-38G
Shat does irinotecan rely on for activty?
Intact lactone ring
What does irinotecan fight against?
Colon cancer and GI cancers
What is the DLT of Ironotecan?
Diarrhea
- drug can be given for extended periods
