Anthracycline antibiotic

Mechanism: intercalates into DNA and generates free radicals (w/cytochrome p450 reductase)

Uses: AIDS related Kaposi's sarcoma (liposomal formulation), acute leukemia, malignant lymphoma, breast cancer

S.E: red urine, BM suppression cardiomyopathy, mutagenic, carcinogenic

Anthracycline antibiotic

Mechanism: intercalates into DNA and generates free radicals (w/cytochrome p450 reductase)

Uses: AIDS related Kaposi's sarcoma (liposomal formulation, AML, ALL

Antitumor antibiotic

Mechanism: intercalates into DNA 

Uses: childhood neoplasms (e.g. Wilm's tumor, Ewing's sarcoma, rhabdosarcoma), testicular tumors, choriocarcinoma 

S.E: anorexia, nausea, vomiting, hematopoetic suppression, dermatological manifestations 

Antitumor antibiotic

Mechanism: binds to DNA to cause strand breakage

Uses: advanced prostate cancer, low-grade non-Hodgkin's lymphoma, breast cancer, AML

S.E:  cardiotoxicity, myelosuppression, N/V, mucositis, alopecia, blue discoloration of fingernails, sclera, urine

Antitumor antibiotic

Mechanism: alkylating agent (crosslinks DNA), hypoxic cells more sensitive

Uses: combo therapy with radiation to kill hypoxic tumor cells; squamous cell cancer of anus, cervix, adenocarcinomas of stomach, pancreas, lung, superficial bladder cancer

S.E:  nausea, thrombocytopenia, anemia, leucopenia, mucositis

Synthetic GnRH analogs

Mechanism: biphasic effect on the pituitary (initial stimulation of LH and FSH, followed by inhibition of LH and FSH release) to decrease testosterone to castration levels and estrogen to postmenopausal levels

Uses: prostate and breast cancer

S.E: hot flashes, sweating, nausea, fatigue, decrease in bone & muscle mass, gynecomastia, hematuria, vaginal bleeding, amenorrhea, impotence, testicular atrophy

Mechanism: aromatase inhibitor (inhibits conversion of androgens to estrogens); inhibits conversion of cholesterol to pregnenolone

Uses: adrenocortical carcinoma, Cushing's syndrome, metastatic breast cancer

 S.E: lethargy, visual blurring, drowsiness, ataxia, skin rashes

Mechanism: camptothecin (topoisomerase I inhibitor)

Uses (2nd line): advanced ovarian cancer, small cell lung cancer 

S.E: myelosuppression, diarrhea

Drug excreted by kidneys

Mechanism: camptothecin (topoisomerase I inhibitor); prodrug (converted to active form in liver)

Uses: metastatic colorectal cancer 

S.E: myelosuppression, diarrhea

Drug excreted by liver 

Mechanism: cuts PML-RARα to release functional RARα

Use: APL w/ t(15:17)

S.E: retinoic acid syndrome (fever, leukocytosis, dyspnea, wt. gain, diffuse pulmonary infiltrate, pleural/pericardial effusion), inc. serum cholesterol and triglyceride levels, CNS toxicity, abdominal pain, diarrhea, transient liver dysfunction, teratogenic

Mechanism: degrades PML-RARα protein; induces apoptosis

Use: APL refractory to ATRA therapy

S.E: fatigue, electrocardiographic change w/QT prolongation, arrhythmias, fever, dyspnea, skin rash, fluid retention, wt. gain 

Adjuncts to chemotherapy

Mechanism: stimulates proliferation of neutrophils 

Uses: reduce frequency and severity of neutropenic sepsis, prevent infection & shorten hospitalization after BM transplantation

S.E: GM-CSF--fever, malaise, arthralgia, myalgia, capillary leak syndrome, allergy; G-CSF--bone pain, splenic rupture (rare); better tolerated than GM-CSF

Pegfilgrastim is a longer acting G-CSF

Adjunct to chemotherapy

Mechanism: organophosphate analog that preferentially has antioxidant effects on normal cells

Uses: reduce nephrotoxicity assoc. w/cisplatin, reduce xerostomia in patients undergoing radiation therapy, reduce pneumonitis and esophagitis in patients undergoing chemotherapy for lung cancer; stimulates BM growth in patients with MDS