Anti-metabolite

Question 1

Is Tanovea a vessicant?

Answer 1

yes

Question 2

What’s the MOA of Tanovea?

Answer 2

• it’s a double pro-drug
• preferentially deliver PMEG and its active phosphorylated metabolite PMEG diphosphate (PMEGpp) to lymphoid cells while avoiding systemic PMEG exposure
• Cytotoxic activity mediated by PMEG/PMEGpp is by inhibition of nuclear DNA polymerases α, δ, and ε.

Question 3

What are some side effects of Tanovea?

Answer 3

• self-limiting gastrointestinal toxicity and myelosuppression; - cumulative dermatologic changes
• rare delayed (~ 5m) pulmonary fibrosis

Question 4

What kind of skin issue can Tanovea cause?

Answer 4

pruritic focal otitis externa or focal erythemic skin lesions on the dorsum and in the inguinal areas.

Question 5

What’s the DLT for Tanovea?

Answer 5

• derm
• GI
• Neutropenia

Question 6

What mutation can lead to resistance in Tanovea?

Answer 6

• mutation in adenosine deaminase-like protein can lead to resistance to tanovea –> inhibits the initial conversion of cPrPMEDAP to PMEG