Heme Onc and Immuno Drugs

• Inhibits calcineurin --> dec'd T-cell differentiation & activation.
• SE's: Nephrotoxicity, lymphomas

• Inhibits cytokine release from T-cells (IL-2). Binds FK-binding protein.
• SE's: Many systems -- nephrotoxicity, pleural effusion, peripheral neuropathy, HTN, hyperglycemia

• Inhibits nucleic acid synthesis, which targets proliferating lymphocytes.
• SE's: bone marrow suppression. Metabolized by xanthine oxidase, so allopurinol may make it toxic.

• Monoclonal Ab that binds CD3 (on all T-cells) --> no signal transduction.
• SE's: Hypersensitivity reaction, cytokine release syndrome

• Blocks T-cell proliferation in response to IL-2, by binding mTOR.
• SE's: leukopenia, thrombocytopenia, hyperlipidemia

Inhibits guanine synthesis --> dec'd lymphocyte production.

Monoclonal Ab against IL-2 receptor on activated T-cells.

(IL-2): renal cell carcinoma, metastatic melanoma

G-CSF. SE's: bone pain

GM-CSF. SE's: bone pain, thrombophlebitis at injection site, fever, rash, pleural effusion

Inhibits viral replication; given for Hepatitis B & C, malignant melanoma, leukemias, Kaposi's sarcoma

Alpha-interferon and IL-2

Inhibits viral replication; given for multiple sclerosis

Given for chronic granulomatous disease. (Neutrophils not working due to NADPH oxidase deficiency, so stimulate macrophages?)

• Anti-neoplastic: alkylating agent at guanine N-7 (remember that P bonds exist in DNA, & alkylating agents create bridges between DNA strands).
• SE's: bone marrow suppression, hemorrhagic cystitis (give mesna)
• Use for: NHL, breast, & ovarian cancer

• "Tricks" DHF reductase into thinking it's folic acid --> DHF reductase inhibition --> dec'd thymine synthesis.
• SE's: BM suppression (reverse w/leucovorin), liver fatty change (macrovesicles -- should be micro- since metabolic cause, but this is significant injury)
• Used for: leukemias & lymphomas, choriocarcinomas, sarcomas... also abortion/ectopic pregnancy, RA, psoriasis

• Can be used with methotrexate, but in case some folic acid is still made... 5-F + dUMP + folic acid --> inhibit thymidylate synthase. It's a pyrimidine analog.
• SE's: Bone marrow suppression (thymidine), photosensitivity
• Uses: Solid tumors -- colon, breast, basal cell carcinoma. Not leukemia/lymphoma.

• Inhibits de novo purine nucleotide synthesis (i.e. IMP --> XMP + AMP).
• SE's: bone marrow suppression; liver; metabolized by xanthine oxidase, so allopurinol increases toxicity (just like azathioprine)

Azathioprine, 6-MP (inhib purine synthesis)

• Anti-neoplastic; inhibits DNA polymerase. It's a pyramidine nucleoside analog.
• Uses: AML, ALL, NHL (high-grade, obv)
• SE's: BM suppression (the anemia is megaloblastic)

• Alkylating agent (at guanine N-7), must be activated by liver.
• SE's: BM suppression, nephro- and neurotoxic

Alkylating agents (anti-neoplastic). Cross blood-brain barrier, so use for glioblastomas & other brain tumors... but CNS toxicity (dizzy, ataxia), & also renal & hepatic.

• DNA cross-linking (just like an alkylating agent).
• SE's: not BM suppression, but nephro- and neurotoxic, plus CN 8 damage
• Uses: Ovary, testicle, bladder, & lung cancer

• Alkylating agent, used for CML & P.vera.
• SE's: pulm fibrosis, hyperpigmentation

• Like dogs: take bites out of DNA (i.e. intercalation of DNA).
• Uses: ABVD for Hodgkin's, plus myelomas, & solid tumors
• SE's: BM suppression, bald, cardiotoxic (not true for dactinomycin, which is used to treat Wilms' tumor, Ewing's sarcoma, & rhabdomyosarcoma)

• Free radicals --> DNA strand breaks.
• SE's: Minimal BM toxicity (bleomycin), but pulm fibrosis, skin changes
• Uses: Part of ABVD for Hodgkin's; testicular cancer

• Inhibits ribonucleotide reductase --> dec'd DNA synthesis
• Uses: Melanoma, CML, sickle-cell (to inc fetal hemoglobin)
• SE's: BM suppression, GI

• Inhibits topoisomerase II, inc's DNA degradation. Specific for G2 (right before mitosis).
• Uses: Small-cell of lung & prostate, testicular cancer
• Toxicity: BM suppression, GI, bald

• SERM: agonize estrogen receptors in bone (& endometrium --> endometrial cancer risk), but antagonize those in breast.
• Used to prevent osteoporosis.

• Anti-CD20 monoclonal Ab. For NHL (since most of these = B-cells, except for lymphoblastic lymphoma & some cases of diffuse lymphoma)
• When the drug is an Ab, cells die via complement-mediated lysis.

• TRIBE: anti-HER-2 receptor Ab, so kills breast cancer cells for which HER-2 is upregulated.
• SE's: cardiotoxicity (this tribe doesn't have a heart)

• Bind tubulin, so microtubules can't polymerize --> no mitotic spindle.
• Uses: Hodgkin's (MOPP), Wilms' tumor, choriocarcinoma
• SE's: neurotoxic, paralytic ileus

• Inhibits mitotic spindle disassembly, by hyperstabilizing the polymerized microtubules. (No anaphase.)
• Uses: ovarian & breast cancer (because women like to hang on to relationships & not disassemble)
• SE's: BM suppression, hypersensitivity