What is the overall MOA of alkylating agents, where do they effect the cell cycle, and what type of cell is most susceptible?
Transfer alkyl groups to DNA which is lethal
Arrest the cell cycle in late G1 and early S
Rapidly dividing cells are most susceptible
What is the most widely used alkylating agent?
Cyclophosphamide
How does cyclophosphamide and isosfamide become active in the body?
Need cyp 450 system to metabolize them into active form.
3 big time adverse effects for cyclo?
Anything that includes rapidly dividing cells
Hemorrhagic cystitis
Secondary malignancies because it is carcinogenic and mutagenic
6 tumors we treat with cyclo or Ifo? How would we describe cyclo’s coverage?
NHL Other lymphoid malignancies Breast Ovarian Solid tumors in kids Burkitt Broad
What tumor do we treat with mechlorethamine?
Topically for cutaneous T cell lymphoma
What cancer do we treat melphalan with?
MM with dexamethasone
What cancer do we use Chlorambucil for?
CLL
What do we use nitrusoureas for, what types of tumors and why?
Brain tumors because they can cross the blood brain barrier
Most significant AE of carmustine? What is the cancer carmustine is used for?
Profound and delayed myelosuppression
Malignant gliomas
2 cancers we use streptozocin for and why?
Carcinoid tumors
Pancreatic islet cell carcinoma
What do we use Thiotepa for?
Blood malignancies
What cancer do we use busulfan for?
CML
What is the most carcinogenic alkylating agents and what 2 cancers do we use it for?
Procarbazine
Hodgkin disease
Gliomas
Big time adverse effect of dacarbazine and what is the primary clinical indication?
NV
Hodgkin disease
3 AE of cisplatin and what 2 cancers do we use cisplatin on 1 other that responds well?
Nephrotixcity if don’t pre treat for chloride and hydration
Ototoxicty
NV
Testicular (with bleomycin and etoposide) and ovarian cancer (with paclitaxel) and lung
When would be good to use carboplatin and what 2 cancers do we use it for?
Because its side effects are less than cisplatin, we can use it for anyone with renal impairment, or experiencing any of the side effects of cisplatin.
Ovary and lung cancer
What is the dose limiting toxicity for carboplastin and oxaliplatin?
Thrombocytopenia
Neurotoxicity
What 2 cancers do we use oxaliplatin for?
Colorectal and GI
What are the 6 classes under alkylating agents?
Bis, nitrosoureas, aziridines, aklysulfonate, non classic, and platinum analogs.
3 mechanisms of resistance to alkylating agents?
DNA repair increase like MGMT
Stop transporting the alkylating agent in the cell
Ramp up glutathione
