Chemotherapy, Immunotherapy, Anemia Drugs

Alkylating Agents (6)

Mechlorethamine

Cyclophosphamide

Carmustine

Lomustine

Busulfan

Streptozocin

Mustards? (2)

Mechlorethamine

Cyclophosphamide

Mechlorethamine Indication

Hodgkin's lymphoma

Mechlorethamine DLT

BMD

Cyclophosphamide mechanism

prodrug requiring hepatic metabolism to form active alkylating agent

Cyclophosphamide indication

CLL, Hodgkin's non-Hodgkins, multiple myeloma, some solid tumors, severe RA

Cyclophosphamide DLT

BMD

Cyclophosphamide side effects/principal toxicities

hemorrhagic cystitis, immunosuppression, alopecia, severe toxicity in patients with renal failure

This is used to protect the bladder lining when taking cyclophosphamide

Mesna

How does Mesna work?

detoxifies acrolein, a metabolite of cyclophosphamide that damages the bladder

Nitrosureas? (3)

Carmustine

Lomustine

Streptozocin

Carmustine and Lomustine are ______ drugs able to cross the _______

lipophilic; BBB

Carmustine and Lomustine indication

primary and metastatic CNS tumors, malignant melanoma, Hodgkin's, multiple myeloma, lung cancers

Carmustine and Lomustine DLT

Delayed BMD

Carmustine and Lomustine side effects/principle toxicities

leucopenia and thrombocytopenia 4-6 weeks after therapy

Streptozocin is retained where?

in pancreatic islet cells

Streptozotocin indiciation

metastatic islet cell carcinoma

Streptozotocin side effects/principal toxicities

renal and hepatic toxicity, insulin shock, BMD

Methane Sulfonates?

Busulfan

Busulfan mechanism

produces a depression of granulocytes in low doses

Busulfan indication

chronic granulocytic leukemia

Busulfan DLT

BMD, pulm fibrosis

Busulfan side effects/principal toxicites

hyperuricemia

What drug should you use concurrently with Busulfan?

allopurinol

Antimetabolites (5)

Methotrexate

6-Mercaptopurine

Thioguanine

5-Fluorouracil

Cytarabine

Methotrexate mechanism

inhibits dihydrofolate reductase, prevents RNA and protein synthesis. kills cells in S-phase

Methotrexate indication

osteogenic sarcoma, gestational choriocarcinoma, lymphocytic leukemia, RA

Methotrexate side effects

BMD, oral and GI ulceration, hepatotoxicity

This drug is used to rescue normal marrow cells when undergoing high dose methotrexate treatment

Leucovorin

Purine analogs? (2)

6-MP

6-TG

6-Mercaptopurine mechanism

prodrug activated by HGPRTase into the nucleotide form 6-MPRP which acts as feedback inhibitor on initial step in purine synthesis

6-Thioguanine mechanism

prodrug actived by HGPRTase into 6-TGRP which acts as feedback inhibitor on inital step in purine synthesis

6-Mercaptopurine and 6-Thioguanine indication

acute leukemias

6-Mercaptopurine and 6-Thioguanine DLT

BMD

5-Fluorouracil mechanism

inhibits thymidylate synthetase by direct binding to the enzyme

5-Fluorouracil indication

breast cancer, colorectal cancer, topical treatment of precancerous solar keratoses and basal cell carcinoma

5-Fluorouracil side effects

BMD, oral and GI ulceration, cerebellar dysfunction, alopecia, skin pigmentation, photosensitivity

Cytarabine mechanism

converted to ara-CTP that inhibits DNA replication. S phase specific

cytarabine resistance

decreased deoxycytidine kinase activity; decreased affinity of polymerase for ara-CTP; increased cytidine deaminase

Cytarabine indication

AML

Cytarabine DLT

BMD

Cytarabine side effects/principal toxicities

Megaloblastosis, oral ulceration

Cytarabine has resistance in what patients?

patients with decreased deoxycytidine kinase activity

Antitumor Antibiotics (5)

Dactinomycin

Doxorubicin

Daunorubicin

Mitomycin

Bleomycin

Intercalators (3)

Dactinomycin

Doxorubicin

Daunorubicin

Dactinomycin, Doxorubicin, Daunorubicin mechanism

intercalating agent that binds to DNA and prevents RNA synthesis

Dactinomycin indication

pediatric cancers - Wilm's tumor, Ewing's sarcoma, embryonal rhabdosarcoma, testicular tumors and sarcomas, choriocarcinoma

Dactinomycin side effects/principal toxicities

BMD, oral and GI ulceration, alopecia, potentiation of radiation reactions

Doxorubicin indication

wide spectrum - lung carcinoma (small cell), breast cancer, bladder tumors, etc.

Daunorubicin indication

acute lymphocytic and granulocytic leukemias

Doxorubicin and Daunorubicin DLT

myelosuppression (leucopenia), cardiotoxicity

Doxorubicin and Daunorubicin side effects

stomatitis, alopecia

This drug is used to chelate iron and reduce cardiotoxicity when undergoing Doxorubicin or Daunorubicin treatment

Dexrazoxane

Non-intercalators (2)

Mitomycin

Bleomycin

Bleomycin mechanism

non-intercalating agent used in combo with other agents

Bleomycin indication

testicular and squamous cell carcinomas, lymphomas

Bleomycin DLT

PF

Bleomycin side effects/principal toxicities

pneumonitis, fevers and chills, anaphylactoid rxns in lymphoma patients, hyperpigmentation and other cutaneous rxns, stomatitis, alopecia

Mitomycin MOA

activated by microsomal enzymes; metabolite reacts with DNA to produce single-strand breakage and cross-link double strands

Mitomycin indication

adenocarcinomas of stomach and pancreas

Mitomycin DLT

cumulative BMD

Mitomycin side effects/principal toxicities

delayed, alopecia, stomatitis, rare renal toxicity

Hormonal Agents (5)

Tamoxifen

Medroxyprogesterone

Leuprolide

Prednisone

Anastrozole

Tamoxifen mechanism

anti-estrogen that inhibits estrogen stimulation of receptor

Tamoxifen indication

post-menopausal estrogen-receptor + breast cancer

Tamoxifen side effects/principal toxicities

low estrogen state - hot flashes, loss of libido, osteoporosis, etc.

Anastrozole mechanism

inhibits estrogen synthesis by inhibiting the aromatase enzyme

Anastrozole treatment

post-menopausal breast cancer

Anastrozole side effects/principal toxicities

hot flashes, bone pain, dyspnea

Medroxyprogesterone acetate indication

endometrial carcinomas previously treated by surgery and radiotherapy; disseminated breast carcinomas

Medroxyprogesterone acetate principal toxicities

mild fluid retention, hypercalcemia

Testosterone propionate indication

advanced breast cancer in patients who are 1-5 years postmenopausal

Testosterone propionate principal toxicities

masculinization, fluid retention, hypercalcemia

Leuprolide mechanism

GnRH analog that inhibits the release of LH and FSH

Leuprolide indiciation

prostate and breast cancer

Leuprolide side effects

"flare" response due to initial increase in LH and FSH release; peripheral edema, infertility

Prednisone mechanism

glucocorticoid that is cytolytic to immature lymphocytes; Not myelosuppressive

Prednisone indication

ALL, CLL, Hodgkin's, multiple myeloma, lymphocytic lymphoma, histiocytic lymphoma, advanced breast cancer

Prednisone side effects

suppression of immune response, osteoporosis, peptic ulceration, immune suppression

Vinca Alkaloids (2)

Vincristine

Vinblastine

Vincristine and Vinblastine resistance

primarily decreased net drug accumulation, often via MDR-P glycoprotein transporter

Vincristine and Vinblastine mechanism

microtubule inhibitor that is M-phase specific

Vincristine indication

ALL in combo with prednisone, Hodgkin's lymphoma, AML, non-Hodgkin's, peds solid tumors, some adult solid tumors

Vincristine DLT

peripheral neuropathies; bone marrow sparing

Vinblastine indication

Hodgkin's and non-Hodgkin's lymphomas, testicular cancer, methotrexate resistant gestational choriocarcinoma

Vinblastine DLT

BMD

Vincristine side effects

local reaction after extravasation, alopecia

Vinblastine side effects

local reaction after extravasation, alopecia; stomatitis

Asparaginase mechanism

deprives tumor cells of asparagine

Asparaginase indication

ALL

Asparaginase DLT

bone marrow sparing

Asparaginase side effects

anaphylaxis, hepatotoxicity, pancreatitis, abd pain, coagulation defects, CNS depression

Hydroxyurea MOA

inhibits ribonucleotide reductase, blocking DNA synthesis. S-phase specific

Hydroxyurea indication

busulfan-resistant chronic granulocytic leukemia; sickle-cell anemia

Hydroxyurea DLT

BMD

Hydroxyurea side effects

stomatitis, derm reactions

Procarbazine MOA

reacts with DNA causing extensive damage. resistance develops rapidly

Procarbazine indications

Hodgkins, non-Hodgkins, small cell lung cancer, malignant melanoma, brain tumors

Procarbazine DLT

BMD

Procarbazine side effects/principle toxicities

CNS depression, stomatitis, CNS toxicity, adrenal insufficiency