TABLE 144- 2. COMMONLY USED ANTINEOPLASTIC DRUGS

TABLE 144- 2. COMMONLY USED ANTINEOPLASTIC DRUGS
Drug Class	Drug	Usual Dosage and Route	Mechanism of Action	Cycle	Commonly Responsive Tumors	Toxicity and Remarks
Alkylating drugs	Mechlorethamine (nitrogen mustard) Chlorambucil (Leukeran) Cyclophosphamide (Cytoxan) Melphalan (Alkeran) Ifosfamide (Ifex)	6 mg/m² IV 4-10 mg/day po 600 mg/m² IV 50-200 mg/m² po 1 mg/kg po q 4 wk 2-4 g/m²/day IV x 3-5 days q 3-4 wk	Alkylate DNA with restricted uncoiling and replication of strands	Non-specific	Hodgkin's disease, malignant lymphoma, small cell lung cancer, breast and testicular cancer, chronic lymphocytic leukemia	Alopecia with high IV dosage; nausea and vomiting; myelosuppression; hemorrhagic cystitis (especially with ifosfamide), which can be ameliorated with mesna; mutagenic and leukemogenic; aspermia; permanent sterility (possible)
Antimetabolites
Folate antagonist	Methotrexate	2.5-5.0 mg/day po 25-50 mg/1 dose/wk po 100-10,000 mg/m²IV (with rescue)	Binds to dihydrofolate reductase and interferes with (pyrimidine) thymidylate synthesis	S-phase-specific	Choriocarcinoma (female), head and neck cancer, acute lymphocytic leukemia, ovarian cancer, malignant lymphoma, osteogenic sarcoma	Mucosal ulceration; bone marrow suppression; increased toxicity with impaired renal function or ascitic fluid (with pooling of drug); leucovorin rescue can reverse toxicity at 24 h (10-20 mg q 6 h x 10 doses)
Purine antagonist	6-Mercaptopurine	100 mg/m²/day po	Blocks de novo purine synthesis	S-phase-specific	Acute leukemia	Myelosuppression, alopecia
Pyrimidine antagonist	5-Fluorouracil	300-1000/m² IV or continuous infusion	Interferes with thymidylate synthase to reduce thymidine production	S-phase-specific	Gastrointestinal neoplasms, breast cancer	Mucositis, alopecia, myelosuppression, diarrhea and vomiting, hyperpigmentation; significant synergistic effect when given after methotrexate
	Cytarabine	100 mg/m² IV continuous infusion	Inhibits DNA polymerase	S-phase-specific	Acute leukemia (especially non-lymphocytic), malignant lymphoma	Myelosuppression, nausea and vomiting, cerebellar and conjunctival toxicities at high dosage, skin rash
	Gemcitabine (Gemzar)	1200 g/m²/wk IV	Interferes with conversion of dCMP to dUMP, thereby limiting the pool of thymidine available	S-phase-specific	Pancreatic, lung, and bladder cancer	Myelosuppression
Spindle poison (from plants)
Vincas	Vinblastine (Velban)	0.1-0.2 mg/kg IV q 7-10 days	Arrests mitosis by alteration of microtubular proteins	Metaphase	Lymphomas, leukemias, breast cancer, Ewing's sarcoma, testicular cancer	Alopecia, myelosuppression, peripheral neuropathy, ileus
	Vincristine (Oncovin)	1.4 mg/m² IV^a	Same as vinblastine	Metaphase	Same as vinblastine	Peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion
	Vinorelbine (Navelbine)	20 mg/m²/wk IV	Same as vinblastine	Metaphase	Lung and breast cancer	Myelosuppression, neuropathy
	Paclitaxel (Taxol)	135 mg-200 g/mL IV q 3 wk	Promotes assembly of microtubules	G₂ and metaphase arrest	Breast, lung, ovarian, head and neck, and bladder cancer	Myelosuppression, alopecia, myalgia, arthralgia, neuropathy
	Docetaxel (Taxotere)	100 g/m² IV q 3 wk	Promotes assembly of microtubules	G₂ and metaphase arrest	Breast and lung cancer	Myelosuppression, alopecia, skin rash, fluid retention
Podophyllotoxins	Etoposide (VePesid)	100 mg/m²/day IV for 3-5 days 100 mg/day po for 14 days/mo	Inhibits mitosis by unknown mechanisms; inhibits topoisomerase II	Metaphase	Lymphoma, Hodgkin's disease, testicular cancer, lung cancer (especially small cell), acute leukemia	Nausea, vomiting, myelosuppression, peripheral neuropathy; cleared by liver (teniposide by kidney); increased toxicity in renal failure
	Irinotecan (Camptosar)	100-125 g/m²/wk IV	Inhibits topoisomerase I	Non-specific	Colon, rectal, and lung cancer	Diarrhea, myelosuppression, alopecia
	Topotecan (Hycamtin)	1.5g/m² IV daily × 5 days q 3-4 wk	Inhibits topoisomerase I	Non-specific	Ovarian and lung cancer	Myelosuppression
Antibiotics	Doxorubicin (Adriamycin)	40-75 mg/m² rapidly IV or 30 mg/m²/day for 3 days by continuous IV^b	Inhibits uncoiling of DNA by intercalation between DNA strands	Non-specific	Acute leukemia, Hodgkin's disease, other lymphomas, breast and lung cancer	Nausea and vomiting, myelosuppression, alopecia; cardiac toxicity at cumulative dosage > 500 mg/m² ; daunomycin, a related derivative, has greater cardiac toxicity; its role has been limited to acute leukemia
	Bleomycin (Blenoxane)	6-15 U/ m² sc or IV	Causes incision of DNA strands	Non-specific	Squamous cell cancer, lymphoma, testicular and lung cancer	Anaphylaxis, chills and fever, skin rash; pulmonary fibrosis at dosage > 200 mg/m² ; requires renal excretion
	Mitomycin	Usually 10 to 12 mg/m², slowly IV	Inhibits DNA synthesis by acting as a bifunctional alkylator	Not cycle- or phase-specific; effects are maximized if cells are in late G or early S phase	Gastric adenocarcinoma; colon, breast, and lung cancer; transitional cell cancer of the bladder	Local extravasation causes tissue necrosis; myelosuppression, with leukopenia and thrombocytopenia 4 to 6 wk after treatment; alopecia; lethargy; fever; hemolytic-uremic syndrome
Nitrosoureas	Carmustine (BiCNU)	150-200 mg/m² IV q 6 wk	Alkylates DNA with restricted uncoiling and replication of strands	Non-specific	Brain tumors, lymphoma	Myelosuppression, pulmonary toxicity (fibrosis), renal toxicity
	Lomustine (CeeNU)	100-130 mg/m² po q 6 wk	Carbamoylation of amino acids in proteins	Non-specific	Brain tumors, (astrocytoma, glioblastoma)	Myelosuppression (delayed), nephrotoxicity
Inorganic ions	Cisplatin (Platinol)	60-100 mg/m² IV or 20 mg/m² IV daily x 5 days	Intercalation and intracalation between DNA strands inhibits uncoiling of DNA	Non-specific	Lung cancer (especially small cell); testicular, breast, and gastric cancer; lymphoma	Anemia, ototoxicity, nausea, vomiting, peripheral neuropathy, myelosuppression
	Carboplatin (Paraplatin)	300 g/m² or target area under the curve of 5-6 IV q 3 wk	Same as cisplatin	Non-specific	Lung, head and neck, and breast cancer	Myelosuppression
Biologic response modifiers	Interferon (Intron A, Roferon-A)	3-25 x 10⁶ U/m² 3 times/wk sc or IV	Antiproliferative effect	Unknown	Hairy cell leukemia, chronic myelogenous leukemia, lymphomas, Kaposi's sarcoma (AIDS), renal cell cancer, melanoma	Fatigue, fever, myalgias, arthralgias, myelosuppression, nephrotic syndrome (rarely)
Enzymes	Asparaginase (Elspar)	1000-6000 U/m² IV or IM	Depletion of asparagine, on which leukemic cells depend	Cycle-specific	Acute lymphocytic leukemia	Acute anaphylaxis, hyperthermia, pancreatitis, hyperglycemia, hypofibrinogenemia
Hormones	Tamoxifen (Nolvadex)	10 mg po bid	Places cells at rest; binding of estrogen receptor	Non-specific	Breast cancer	Hot flushes, hypercalcemia, deep vein thrombosis
	Leuprolide (Lupron)	7.5 mg/mo IM or depot 21 mg IM q 3 mo	Inhibits gonadotropin secretion	Non-specific	Prostate cancer	Hot flushes, decreased libido, irritation at injection site
	Flutamide (Eulexin)	250 mg po q 8 h	Binds the androgen receptor		Prostate cancer	Decreased libido, hot flushes, gynecomastia
	Megestrol acetate (Megace)	160-240 mg/day po	Inhibits estrogen action	Non-specific	Breast and endometrial cancer	Weight gain, fluid retention
^aDose commonly "capped" at a total of 2 mg in adults.
^bHigher dosage tolerated when given by continuous IV.
dCMP = deoxycytidine monophosphate; dUMP = deoxyuridine monophosphate.

TABLE 144- 2. COMMONLY USED ANTINEOPLASTIC DRUGS
Drug Class	Drug	Usual Dosage and Route	Mechanism of Action	Cycle	Commonly Responsive Tumors	Toxicity and Remarks
Alkylating drugs	Mechlorethamine (nitrogen mustard) Chlorambucil (Leukeran) Cyclophosphamide (Cytoxan) Melphalan (Alkeran) Ifosfamide (Ifex)	6 mg/m² IV 4-10 mg/day po 600 mg/m² IV 50-200 mg/m² po 1 mg/kg po q 4 wk 2-4 g/m²/day IV x 3-5 days q 3-4 wk	Alkylate DNA with restricted uncoiling and replication of strands	Non-specific	Hodgkin's disease, malignant lymphoma, small cell lung cancer, breast and testicular cancer, chronic lymphocytic leukemia	Alopecia with high IV dosage; nausea and vomiting; myelosuppression; hemorrhagic cystitis (especially with ifosfamide), which can be ameliorated with mesna; mutagenic and leukemogenic; aspermia; permanent sterility (possible)
Antimetabolites
Folate antagonist	Methotrexate	2.5-5.0 mg/day po 25-50 mg/1 dose/wk po 100-10,000 mg/m²IV (with rescue)	Binds to dihydrofolate reductase and interferes with (pyrimidine) thymidylate synthesis	S-phase-specific	Choriocarcinoma (female), head and neck cancer, acute lymphocytic leukemia, ovarian cancer, malignant lymphoma, osteogenic sarcoma	Mucosal ulceration; bone marrow suppression; increased toxicity with impaired renal function or ascitic fluid (with pooling of drug); leucovorin rescue can reverse toxicity at 24 h (10-20 mg q 6 h x 10 doses)
Purine antagonist	6-Mercaptopurine	100 mg/m²/day po	Blocks de novo purine synthesis	S-phase-specific	Acute leukemia	Myelosuppression, alopecia
Pyrimidine antagonist	5-Fluorouracil	300-1000/m² IV or continuous infusion	Interferes with thymidylate synthase to reduce thymidine production	S-phase-specific	Gastrointestinal neoplasms, breast cancer	Mucositis, alopecia, myelosuppression, diarrhea and vomiting, hyperpigmentation; significant synergistic effect when given after methotrexate
	Cytarabine	100 mg/m² IV continuous infusion	Inhibits DNA polymerase	S-phase-specific	Acute leukemia (especially non-lymphocytic), malignant lymphoma	Myelosuppression, nausea and vomiting, cerebellar and conjunctival toxicities at high dosage, skin rash
	Gemcitabine (Gemzar)	1200 g/m²/wk IV	Interferes with conversion of dCMP to dUMP, thereby limiting the pool of thymidine available	S-phase-specific	Pancreatic, lung, and bladder cancer	Myelosuppression
Spindle poison (from plants)
Vincas	Vinblastine (Velban)	0.1-0.2 mg/kg IV q 7-10 days	Arrests mitosis by alteration of microtubular proteins	Metaphase	Lymphomas, leukemias, breast cancer, Ewing's sarcoma, testicular cancer	Alopecia, myelosuppression, peripheral neuropathy, ileus
	Vincristine (Oncovin)	1.4 mg/m² IV^a	Same as vinblastine	Metaphase	Same as vinblastine	Peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion
	Vinorelbine (Navelbine)	20 mg/m²/wk IV	Same as vinblastine	Metaphase	Lung and breast cancer	Myelosuppression, neuropathy
	Paclitaxel (Taxol)	135 mg-200 g/mL IV q 3 wk	Promotes assembly of microtubules	G₂ and metaphase arrest	Breast, lung, ovarian, head and neck, and bladder cancer	Myelosuppression, alopecia, myalgia, arthralgia, neuropathy
	Docetaxel (Taxotere)	100 g/m² IV q 3 wk	Promotes assembly of microtubules	G₂ and metaphase arrest	Breast and lung cancer	Myelosuppression, alopecia, skin rash, fluid retention
Podophyllotoxins	Etoposide (VePesid)	100 mg/m²/day IV for 3-5 days 100 mg/day po for 14 days/mo	Inhibits mitosis by unknown mechanisms; inhibits topoisomerase II	Metaphase	Lymphoma, Hodgkin's disease, testicular cancer, lung cancer (especially small cell), acute leukemia	Nausea, vomiting, myelosuppression, peripheral neuropathy; cleared by liver (teniposide by kidney); increased toxicity in renal failure
	Irinotecan (Camptosar)	100-125 g/m²/wk IV	Inhibits topoisomerase I	Non-specific	Colon, rectal, and lung cancer	Diarrhea, myelosuppression, alopecia
	Topotecan (Hycamtin)	1.5g/m² IV daily × 5 days q 3-4 wk	Inhibits topoisomerase I	Non-specific	Ovarian and lung cancer	Myelosuppression
Antibiotics	Doxorubicin (Adriamycin)	40-75 mg/m² rapidly IV or 30 mg/m²/day for 3 days by continuous IV^b	Inhibits uncoiling of DNA by intercalation between DNA strands	Non-specific	Acute leukemia, Hodgkin's disease, other lymphomas, breast and lung cancer	Nausea and vomiting, myelosuppression, alopecia; cardiac toxicity at cumulative dosage > 500 mg/m² ; daunomycin, a related derivative, has greater cardiac toxicity; its role has been limited to acute leukemia
	Bleomycin (Blenoxane)	6-15 U/ m² sc or IV	Causes incision of DNA strands	Non-specific	Squamous cell cancer, lymphoma, testicular and lung cancer	Anaphylaxis, chills and fever, skin rash; pulmonary fibrosis at dosage > 200 mg/m² ; requires renal excretion
	Mitomycin	Usually 10 to 12 mg/m², slowly IV	Inhibits DNA synthesis by acting as a bifunctional alkylator	Not cycle- or phase-specific; effects are maximized if cells are in late G or early S phase	Gastric adenocarcinoma; colon, breast, and lung cancer; transitional cell cancer of the bladder	Local extravasation causes tissue necrosis; myelosuppression, with leukopenia and thrombocytopenia 4 to 6 wk after treatment; alopecia; lethargy; fever; hemolytic-uremic syndrome
Nitrosoureas	Carmustine (BiCNU)	150-200 mg/m² IV q 6 wk	Alkylates DNA with restricted uncoiling and replication of strands	Non-specific	Brain tumors, lymphoma	Myelosuppression, pulmonary toxicity (fibrosis), renal toxicity
	Lomustine (CeeNU)	100-130 mg/m² po q 6 wk	Carbamoylation of amino acids in proteins	Non-specific	Brain tumors, (astrocytoma, glioblastoma)	Myelosuppression (delayed), nephrotoxicity
Inorganic ions	Cisplatin (Platinol)	60-100 mg/m² IV or 20 mg/m² IV daily x 5 days	Intercalation and intracalation between DNA strands inhibits uncoiling of DNA	Non-specific	Lung cancer (especially small cell); testicular, breast, and gastric cancer; lymphoma	Anemia, ototoxicity, nausea, vomiting, peripheral neuropathy, myelosuppression
	Carboplatin (Paraplatin)	300 g/m² or target area under the curve of 5-6 IV q 3 wk	Same as cisplatin	Non-specific	Lung, head and neck, and breast cancer	Myelosuppression
Biologic response modifiers	Interferon (Intron A, Roferon-A)	3-25 x 10⁶ U/m² 3 times/wk sc or IV	Antiproliferative effect	Unknown	Hairy cell leukemia, chronic myelogenous leukemia, lymphomas, Kaposi's sarcoma (AIDS), renal cell cancer, melanoma	Fatigue, fever, myalgias, arthralgias, myelosuppression, nephrotic syndrome (rarely)
Enzymes	Asparaginase (Elspar)	1000-6000 U/m² IV or IM	Depletion of asparagine, on which leukemic cells depend	Cycle-specific	Acute lymphocytic leukemia	Acute anaphylaxis, hyperthermia, pancreatitis, hyperglycemia, hypofibrinogenemia
Hormones	Tamoxifen (Nolvadex)	10 mg po bid	Places cells at rest; binding of estrogen receptor	Non-specific	Breast cancer	Hot flushes, hypercalcemia, deep vein thrombosis
	Leuprolide (Lupron)	7.5 mg/mo IM or depot 21 mg IM q 3 mo	Inhibits gonadotropin secretion	Non-specific	Prostate cancer	Hot flushes, decreased libido, irritation at injection site
	Flutamide (Eulexin)	250 mg po q 8 h	Binds the androgen receptor		Prostate cancer	Decreased libido, hot flushes, gynecomastia
	Megestrol acetate (Megace)	160-240 mg/day po	Inhibits estrogen action	Non-specific	Breast and endometrial cancer	Weight gain, fluid retention
^aDose commonly "capped" at a total of 2 mg in adults.
^bHigher dosage tolerated when given by continuous IV.
dCMP = deoxycytidine monophosphate; dUMP = deoxyuridine monophosphate.