log-kill hypothesis

Growth fraction

G₀ phase specific (cancer drugs)

Alkylating agents

antitumor antibiotics

nitrosoureas (lomustine, carmustine)

cisplatin

S phase specific (cancer drugs)

cytarabine

6-mercaptopurine

6-thioguanine

methotrexate

hydroxyurea

etoposide

G₂ phase specific (anticancer)

M phase specific (anticancer)

vinblastine

vincristine

paclitaxel

Cyclophosphamide

MOA: alkylating agent, attacks guanine N7 --> dysfunctional DNA

Uses: Non-Hodgkin, ovarian, breast cancer, neuroblastoma

SE: BMS (bone marrow suppression), hemorrhagic cystitis, hepatic toxicity

Antidote: mesna (traps acrolein and is protective)

Cisplatin

MOA: alkylating agent, cross-links DNA strands

Uses: testicular, ovarian, bladder, lung cancer

SE: N/V (use ondansetron), nephrotoxicity (use amifostine), neurotoxicity (deafness)

Procarbazine

MOA: alkylating agent

Uses: Hodgkin

SE: BMS, pulmonary toxicity, hemolysis, neurotoxicity, leukemogenic

Doxorubicin

MOA: intercalator, forms free radicals, inhibits topoisomerase

Uses: Hodgkin, breast, endometrial, lung, and ovarian

SE: BMS, delayed CHF, alopecia, vesicant, radiation "recall"

Use dexrazoxane as iron-chelating agent to prevent formation of free radicals

Methotrexate

MOA: Antimetabolite-inhibits DHF reductase (S phase)

Uses: leukemias, lymphomas, breast cancer, RA, psoriasis

SE: BMS, mucositis, crystalluria (renal toxicity)

Use leucovorin as folinic acid rescue

5-FU

MOA: pyrimidine antimetabolite (S phase) bioactivated to inhibit thymidylate synthetase

Uses: breast, ovarian, head, and neck cancer, topical for basal cell cancer and keratoses

SE: BMS, GI irritation, alopecia

6-mercaptopurine

MOA: purine antimetabolite (S phase) bioactivated by HGPR transferase

Uses: acute lymphocytic leukemia, immunosuppression

SE: BMS, hepatotoxicity (jaundice, necrosis), GI distress 

Bleomycin

MOA: complexes w/ Fe and O2 --> DNA strand scission (G2 phase)

Uses: hodgkin, testicular, head, neck, skin cancer

SE: Pneumonitis, pulmonary fibrosis, mucocutaneous rxns (blisters), alopecia, hypersensitivity

Vincristine

MOA: dec. microtubular polymerization- spindle poisons (M-phase)

Uses: Hodgkin, leukemias, Wilms

SE: Neurotoxicity

Vinblastine

MOA: dec. microtubluar polymerization- spindle poisons (M phase)

Uses: Hodgkin, testicular cancer, Kaposi

SE: BMS, GI, alopecia

Cyclosporine

MOA: Binds to cyclophilin --> dec. calcineurin (cytoplasmic phosphatase) --> dec. activation of T-cell transcription factors like IL-2, IL-3, and IFN-gamma

Uses: DOC for organ or tissue transplantation

SE: peripheral neuropathy, nephrotoxicity, hyperglycemia, HTN, hyperlipidemia, hirsutism, gingival overgrowth, cholelithiasis

Tacrolimus

MOA: antibiotic w/ immunosuppressant actions, acts similarly to cyclosporine to inhibit calcineurin to dec. activation of T-cell transcription factors

Uses: used alternatively to cyclosporine in renal and liver transplants

Azathioprine

Abciximab

monoclonal antibody

Uses: antiplatelet --> antagonist of IIb/IIIa receptors

Infliximab

monoclonal antibody

Uses: RA, and Crohn's dz (binds TNF)

Trastuzumab

monoclonal antibody

Uses: breast cancer, antagonist to ERB-B2

Dacliximab

monoclonal antibody

Uses: kidney transplants, blocks IL-2 receptors

Muromonab

monoclonal Ab

Uses: kidney transplant - blocks allograft rejection

Palivizumab

monoclonal Ab

Uses: respiratory syncytial virus - blocks protein

Rituximab

monoclonal Ab

Uses: Non-Hodgkin lymphoma - binds to surface protein

Aldesleukin

IL-2

Uses: increases lymphocyte differentiation and inc. NK, used in renal cell cancer and metastatic melanoma

Interleukin-11

Filgrastim

G-CSF

Increases granulocytes used in marrow recovery

Sargramostim

GM-CSF

Increases granulocytes and macrophages, used for bone marrow recovery

Erythropoietin

Anemias, esp assoc. w/ renal failure

Thrombopoietin

IFN-alpha

Hep B,C, leukemias, melanoma

IFN-beta

IFN-gamma