Mitotic inhibitors (M phase)

• Chris Christie closed lanes at George Washington Bridge
  • He is toxic
• Need to take taxi
• People boo

Alkylating agents (G1 phase)

Detoxifying agents for antineoplastic treatment

• Platinum-based agents
  • Prevent Nephrotoxicity
  • Amifostine: free radical scavenger
  • IV saline: induces chloride diuresis → ↑ urine chloride concentration → ↓ cisplatin reactivity
• Oxazaphosphorines
  • Prevent Bladder toxicity
    • Hemorrhagic cystitis
    • Bladder carcinoma
  • Mesna (2-MErcaptoethane Sulfonate Na) and fluids
• Antifolates
  • Prevent
    • Myelosuppression
    • Mucositis
    • Hepatotoxicity
    • Pulmonary fibrosis
  • Leucovorin (folinic acid)
    • Precursor of tetrahydrofolate
    • Application 24 h after the administration of antifolates
• Anthracyclines
  • Prevent Cardiotoxicity
  • Dexrazoxane: iron chelating agent

Antimetabolites (S phase)

• See De novo pyrimidine and purine synthesis
• Azathioprine is the prodrug of 6-MP
  • Azathioprine and 6-MP are purine analogs, so they are metabolized to inactivate forms by xanthine oxidase like purines
  • See Gout > Treatment, Lesch-Nyhan syndrome

Topoisomerase inhibitors (G2 phase)

Mnemonic

• Eight (Etoposide) + II = Ten (Teniposide)
• I (Irinotecan) + I = Two (Topotecan)

Antitumor antibiotics

Mnemonic

• Mnemo I use for Doxorubicin /Daunorubicin:
  • They both end in -rubicin → ruby (= red) → the heart is red → cardiotoxicity
  • Dilated cardiomyopathy because it starts with D like Doxorubicin
  • Dexrazoxane used to prevent it → also starts with D and sounds like Roxane (‘Roxane, you don’t have to put on the red light’, song by the police) → again red for RUBYcin and heart.
• Bleomycin: bleo → fibro

Protein kinase inhibitors

CDK inhibitors

• Palbociclib
• Inhibition of cyclin-dependent kinase 4 and 6 → inhibition of cancer cell growth and induction of apoptosis
• Indications
  • Metastatic breast cancer
  • Myelosuppression
• Side effects
  • Pulmonary toxicity (e.g., pneumonitis)

Anticancer treatment-related complications

Chemotherapy-induced nausea and vomiting (CINV)

• Acute-phase CINV (<24 hours after chemotherapy) is mediated primarily by the release of serotonin from intestinal enterochromaffin cells that have been damaged by chemotherapy. Serotonin stimulates vagal afferent fibers (5-HT3 receptors) in the bowel wall, which project to the brainstem and stimulate the vomiting reflex. Therefore, serotonin receptor antagonists (eg, ondansetron) can be used for treatment.
• Delayed-phase CINV (1-5 days after chemotherapy) is mediated primarily by increased levels of substance P in the brainstem due to chemotherapy-associated emetic stimuli in the cerebrospinal fluid and bloodstream. Substance P binds to and activates the neurokinin-1 (NK1) receptor in areas of the brainstem that mediate vomiting (eg, nucleus tractus solitarius, area postrema). Therefore, NK1 receptor antagonists (eg, aprepitant, fosaprepitant) are often used for treatment.