Lung Cancer

Question 0

Microtubule Inhibitors
Taxanes (paclitaxel, docetaxel, cabazitaxel)
Ixabepilone (Ixempra)

Answer 0

Lung cancer
-administer before platinum compounds (can increase toxicity)
-administer after anthracyclines
-“-taxel”
MOA
-cell cycle specific (G2/M phase)
-“mitotic spindle poison”- high-affinity binding to microtubules
-inhibits depolymerization and enhances polymerization
-reduces tubulin concentration
-promotes microtubule assembly in the absence essential proteins resulting in cell death
ADE
-myelosuppression, neuropathy, fluid retention, diarrhea/nausea/vomit, extensively metabolized by liver
Paclitaxel
-cardiac toxicity, Stevens-Johnson syndrome, hypersensitivity rx, seizure, PE
-cremophor vehicle, abnormal EKGs
Albumin-bound paclitaxel
-cardiac arrest, PE
-no cremophor
Docetaxel
-fluid retention, Stevens-Johnson syndrome, PE, colitis
-*polysorbate 80 vehicle, fluid retention, hand-foot syndrome, nail ridging

Question 1

Platinums

Cisplatin, Carboplatin, Oxaliplatin

Answer 1

Lung cancer
-“-platin”
-mainstay therapy
MOA
-*non cell cycle specific
-intracellular activation via aquation of leaving groups
-forms covalent DNA adducts
-binds to proteins, lipids, RNA, mitochondrial DNA inhibiting DNA biosynthesis
ADE
Cisplatin
-seizure, visual/auditory impairment, hypersensitivity, encephalopathy, *nausea/vomiting high, nephrotoxicity
Carboplatin
-Visual impairment, hypersensitivity, Hematologic issues
-dosed using calvert equation (AUC)
Oxaliplatin
-neuropathy (sensitive to cold), hemolytic anemia, hypersensitivity, pulmonary fibrosis

Question 2

Topoisomerase I Inhibitors
Camptothecin Analogs
(Irinotecan, Topotecan)

Answer 2

Lung cancer
-“-tecan”
MOA
-S-phase specific
-Camptothecin irreversibly binds to topoisomerase I and stabilize the “cleavable complex”
-results in inhibited re-annealing and SS DNA breaks
-DS breaks result during DNA replication when DNA polymerase encounters stabilized cleavable complexes
-accumulation of SS and DS breaks leads to cell death
ADE
Topotecan
-intestinal lung disease
-mylosuppression, arthralgia, alopecia, mild nausea/vomiting, mouth sores
Irinotecan
-SN-38 metabolite responsible for cytotoxic activity
-GI perforation, interstitial lung disease
-mylosuppression, *diarrhea (acute & delayed), mod nausea/vomiting, hair loss/thinning, liver fx abnormalities

Question 3

Topoisomerase II Inhibitor

Epipodophyllotoxins (Etoposide, Teniposide)

Answer 3

Lung cancer
-“-poside”
MOA
-arrests cell in G2/M phase preventing mitosis
-does not bind directly to DNA
-stabilizes the DNA cleavable complex through inhibition of DNA re-ligation
-blocks progression of cell cycle
-inhibition of DNA synthesis lease to apoptosis of the cell
ADE
Etoposide
-hepatotoxicity, CHF, Steven-johnson syndrome, secondary malignancy
-myelosuppression, mild nausea/vomiting/loss of apetite, hair loss/thinning, diarrhea, mucositis, fever/chills, hypersensitivity rx (tween 80)