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Cancer is a disorder of cellular growth, life span, and death. It is a group of abnormal cells that generally proliferate (multiply) more rapidly than normal cells, lose the ability to perform specialized functions, invade surrounding tissues, and develop growths in other tissues distant to the site of original growth (metastases). Many types of cancer cells also lose the ability to die normally as a part of their life cycle. Normal cells have a genetically programmed life cycle that includes a cell death known as apoptosis.

Cancer is a leading cause of death in the United States. Unfortunately, the number of people that die from malignant diseases increases each year. The American Cancer Society estimates new cancer cases in Facts and Figures annually as a means of projecting cancer incidence for the upcoming year (Figure 44-1). Early diagnosis and treatment is still one of the most important factors in providing a more optimistic prognosis for those patients stricken with the many forms of neoplastic disease.

All cells, whether normal or malignant, pass through a similar series of phases during their lifetime, although duration of time spent in each phase differs with the type of cell (Figure 44-2). Mitosis is the phase of cellular proliferation in which the cell divides into two equal daughter cells. Cells either advance into a nonproliferative stage, known as G₀, or advance to the first gap phase, G₁. G₀ is the largest variable in the cell cycle, and during this resting phase the cell is not actively replicating. Some stimulus results in the cell entering the G₁ phase. Phase G₁ is considered a presynthetic phase in which the cell prepares for DNA synthesis by manufacturing necessary enzymes. The S phase is the stage of active synthesis of two sets of DNA. Phase G₂ is a postsynthetic phase in which the cell prepares for mitosis by producing ribonucleic acid (RNA), specialized proteins, and the foundations for mitotic spindle apparatus needed for mitosis. The cell cycle begins again when the mitotic phase divides the cell into two daughter cells. The daughter cells may advance again to the G₁ phase or pass into G₀. The time required to complete one cycle is termed the generation time.

Many antineoplastic agents are cell cycle–specific (i.e., the drug is selectively toxic when the cell is in a specific phase of growth, and therefore is schedule-dependent). Malignancies most amenable to cell cycle–specific chemotherapy are those that proliferate rapidly. Cell cycle–nonspecific drugs are active throughout the cell cycle and may be more effective against slowly proliferating neoplastic tissue. These agents are not schedule-dependent but are dose-dependent. One implication of cell cycle specificity is the importance of correlating the dosage schedule of anticancer therapy with the known cellular kinetics of that type of neoplasm. Drugs are usually administered when the cell is most susceptible to the cytotoxic effects of the agent for a higher “kill rate” of neoplastic cells. Table 44-1 lists the more common commercially available drugs, their general dosage ranges, major toxicities, and major indications.

Table 44-1

Cancer Chemotherapeutic Agents

DRUG	USUAL DOSAGE, ROUTE, AND FREQUENCY	TOXICITY		MAJOR INDICATIONS
		ACUTE	DELAYED
Alkylating Agents
bendamustine (Treanda)	IV: 100 mg/m2 on days 1 and 2 of a 28-day cycle, up to six cycles	Fever, nausea, vomiting	Moderate depression of peripheral blood count	Chronic lymphocytic leukemia
busulfan (Myleran)	PO: 4-8 mg/day for 2-3 wk, stop for recovery, then maintenance	Edema	Bone marrow depression	Chronic myelogenous leukemia
carboplatin	360 mg/m2 q 4 wk as a single agent	Nausea, vomiting	Bone marrow suppression, anemia, nephrotoxicity	Ovarian carcinoma
carmustine (BiCNU)	As single agent: IV: 150-200 mg/m2 over 1- to 2-hr infusion q 6 wk In combination: Dosage individualized Caution: Use gloves because solution may cause skin discoloration	Nausea and vomiting; pain along vein of infusion	Granulocyte and platelet suppression; hepatic, pulmonary, renal toxicity	Brain tumors, Hodgkin’s disease, non-Hodgkin’s lymphoma, multiple myeloma, malignant melanoma
chlorambucil (Leukeran)	PO: Start 0.1-0.2 mg/kg/day; adjust for maintenance	None	Bone marrow depression (anemia, leukopenia, thrombocytopenia) can be severe with excessive dosage	Chronic lymphocytic leukemia, lymphosarcoma, Hodgkin’s disease, non-Hodgkin’s lymphoma
cisplatin	IV: 20-100 mg/m2; frequency highly variable depending on cancer being treated	Nausea, vomiting	Nephrotoxicity, ototoxicity, blurred vision, changes in color perception	Testicular and ovarian cancers, bladder cancer
cyclophosphamide Do not confuse cyclophosphamide with cyclosporine.	IV: 40-50 mg/kg in divided doses over 2-5 days PO: 1-5 mg/kg/day for variable duration; adjust for maintenance	Nausea and vomiting	Bone marrow depression, alopecia, cystitis	Hodgkin’s disease and other lymphomas, multiple myeloma, lymphocytic leukemia, many solid cancers
dacarbazine (DTIC)	IV: 2-4.5 mg/kg/day for 10 days; repeat q 28 days IV: 150 mg/m2 daily for 5 days in 4-wk cycles	Nausea and vomiting, flu-like syndrome	Bone marrow depression (rare)	Metastatic malignant melanoma, Hodgkin’s disease
ifosfamide (Ifex)	IV: 1.2 g/m2/day for 5 days	Nausea, vomiting, diarrhea	Hematuria, alopecia, confusion, coma	Testicular, lung, breast, ovarian, pancreatic, gastric cancer
lomustine (CeeNU)	PO: 100-130 mg/m2 once q 6 wk	Severe nausea and vomiting; anorexia	Thrombocytopenia, leukopenia, alopecia, confusion, lethargy, ataxia	Brain tumors, Hodgkin’s disease
mechlorethamine (nitrogen mustard; Mustargen)	IV: 0.4 mg/kg in single or divided doses over 2 days	Nausea and vomiting	Moderate depression of peripheral blood count	Hodgkin’s disease and other lymphomas, bronchogenic carcinoma
melphalan (Alkeran)	PO: 0.2 mg/kg/day for 5 days; 2-4 mg/day as maintenance or 0.1-0.15 mg/kg/day for 2-3 wk	Nausea, vomiting, diarrhea	Bone marrow depression	Multiple myeloma, ovarian carcinoma, testicular seminoma
oxaliplatin (Eloxatin)	IV: 85 mg/m2; used in combination with leucovorin and 5-fluorouracil	Diarrhea, emesis, fatigue	Anemia, peripheral sensory neuropathy, stomatitis, thrombocytopenia	Colon cancer
streptozocin (Zanosar)	As single agent: daily schedule—500 mg/m2 for 5 consecutive days q 6 wk; weekly schedule—1000 mg/m2 at weekly intervals for 2 wk; assess response Adjust dosage according to response.	Hypoglycemia, severe nausea, vomiting	Moderate but transient renal and hepatic toxicity, hypoglycemia, mild anemia, leukopenia	Pancreatic islet cell carcinoma
temozolomide (Temodar)	PO: 150 mg/m2 once daily for 5 days per 28-day cycle	Headache, nausea, vomiting, constipation	Bone marrow depression, seizures	Glioblastoma, astrocytoma
thiotepa	IV: 0.3-0.4 mg/kg q 1-4 wk	Dizziness, headache, anorexia	Bone marrow depression	Hodgkin’s disease, ovarian, breast, and bladder carcinoma
Antimetabolites
capecitabine (Xeloda)	1250 mg/m2 twice daily for 2 wk, followed by 1 wk of rest	Nausea, vomiting, diarrhea, constipation, fatigue	Bone marrow depression, dermatitis, hand-and-foot syndrome, lymphopenia	Breast cancer, colorectal cancer
cladribine (Leustatin)	IV: 0.09-0.1 mg/kg/day infused over 24 hr for 7 consecutive days	Headache, dizziness, rash, nausea	Bone marrow depression, purpura	Hairy cell leukemia, lymphomas
clofarabine (Clolar)	IV: 52 mg/m2 over 2 hr daily for 5 days	Flushing, hypotension, hypertension, headache, nausea, vomiting	Bone marrow depression, dermatitis	Acute lymphocytic leukemia
cytarabine hydrochloride	Highly variable for condition being treated	Nausea, vomiting, anorexia, oral ulceration	Bone marrow depression, megaloblastosis	Acute leukemias
decitabine (Dacogen)	IV: 15 mg/m2 over 3 hr, repeated q 8 hr for 3 days The cycle is repeated q 6 wk for a minimum of four cycles if tolerated	Nausea, fever, fatigue, cough, diarrhea	Hyperglycemia, anemia, neutropenia, thrombocytopenia, petechiae	Myelodysplastic syndromes (MDS)
floxuridine (FUDR) Do not confuse FUDR with Fludara.	0.1 to 0.6 mg/kg/day by intra-arterial infusion using an implantable pump	Nausea, vomiting, diarrhea	Anemia, leukopenia, thrombocytopenia; hepatotoxicity	GI adenocarcinoma metastatic to the liver; tumors of the liver, ovaries, and kidneys
fludarabine (Fludara) Do not confuse fludarabine with Flumadine. Do not confuse Fludara with FUDR.	25 mg/m2 daily for 5 days; start q 5-day cycle q 28 days	Nausea, vomiting, diarrhea, anorexia, myalgia	Edema, rash, weakness, cough, dyspnea, hemolytic anemia	Chronic lymphocytic leukemia, other leukemias
fluorouracil (Adrucil) Do not confuse fluorouracil with flucytosine or fluocinonide.	IV: 12 mg/kg/day for 4 days, then 6 mg/kg/day on the 6th, 8th, 10th, and 12th days	Nausea	Oral and GI ulceration, stomatitis and diarrhea, bone marrow depression	Breast, large bowel, ovarian, pancreatic, stomach carcinoma
gemcitabine (Gemzar) Do not confuse Gemzar with Zinecard.	IV: 1250 mg/m2 on days 1 and 8 of q 21-day cycle	Nausea, vomiting	Bone marrow suppression, rashes, edema	Pancreatic, ovarian, breast, lung cancer
mercaptopurine (6-MP, Purinethol)	PO: 2.5 mg/kg/day for induction then 1.5 to 2.5 mg/kg/day as maintenance	Occasional nausea, vomiting; usually well tolerated	Bone marrow depression, occasional hepatic damage	Acute lymphocytic leukemia; acute myelogenous leukemia
methotrexate (MTX, Trexall) Do not confuse methotrexate with metolazone. Do not confuse Trexall with Trental or Treanda.	Highly variable for condition being treated	Occasional diarrhea, hepatic necrosis	Oral and GI ulceration, bone marrow depression (anemia, leukopenia, thrombocytopenia), cirrhosis	Acute lymphocytic leukemia, choriocarcinoma, carcinoma of cervix and head and neck area, mycosis fungoides, solid cancers
pemetrexed (Alimta)	IV: 500 mg/m2 over 10 min on day 1 of q 21-day cycle	Nausea, vomiting, diarrhea	Bone marrow depression, renal dysfunction	Malignant pleural mesothelioma, non–small cell lung cancer
pentostatin (Nipent) Do not confuse pentostatin with pentazocine.	IV: 4 mg/m2 over 20-30 min every other wk	Nausea, vomiting, muscle pain, headache, bloating, constipation, diarrhea	Bone marrow depression, renal dysfunction	Hairy cell leukemia, lymphomas
pralatrexate (Folotyn)	IV push: 30 mg/m2 over 3-5 min once weekly for 6 wk in 7-wk cycle	Fatigue, pruritus, constipation, nausea, vomiting, edema, nose bleeds	Bone marrow depression, mucositis	Peripheral T-cell lymphoma
thioguanine (Tabloid)	PO: 2 mg/kg/day	Occasional nausea, vomiting; usually well tolerated	Bone marrow depression	Acute nonlymphocytic leukemia
Natural Products
etoposide (Toposar)	IV: 50-100 mg/m2 daily for 5 days; cycles of therapy are given q 3-4 wk	Nausea (30%-40%), vomiting, stomatitis, diarrhea	Leukopenia, nadir in 10-14 days, recovery in 3 wk; thrombocytopenia; alopecia	Testicular tumors, small cell carcinoma of the lung, Hodgkin’s disease and non-Hodgkin’s lymphoma, acute nonlymphocytic leukemia, ovarian carcinoma, Kaposi’s sarcoma
docetaxel (Taxotere)	IV: 60-100 mg/m2 q 3 wk	Nausea, vomiting, diarrhea	Bone marrow suppression, rashes, hypersensitivity	Breast cancer, prostate cancer; gastric adenocarcinoma, head and neck cancer; non–small cell lung cancer
paclitaxel (Abraxane, Onxol) Do not confuse paclitaxel with Paxil.	Different dosages for cancer being treated and regimen used	Nausea, vomiting, hypotension, diarrhea	Bone marrow suppression, mucositis, peripheral neuropathy	Ovarian carcinoma, breast carcinoma, AIDS-related Kaposi’s sarcoma, lung cancer
teniposide (Vumon)	Variable based on other treatments	Diarrhea, nausea/vomiting	Bone marrow suppression, mucositis	Acute lymphoblastic leukemia
vinblastine sulfate	IV: 3.7 mg/m2/wk or q 2 wk Dosage adjusted based on white cell count	Nausea, vomiting, local irritant	Alopecia, stomatitis, bone marrow depression, loss of reflexes	Hodgkin’s disease and other lymphomas, solid cancers
vincristine sulfate	IV: 1.4 mg/m2/wk once weekly	Local irritant	Areflexia, peripheral neuritis, paralytic ileus, mild bone marrow depression	Acute lymphocytic leukemia, Hodgkin’s disease and other lymphomas, solid cancers
vinorelbine (Navelbine)	IV: 30 mg/m2/wk over 6-10 min once weekly	Nausea, vomiting, constipation, diarrhea	Bone marrow suppression, hepatotoxicity, bronchospasm	Non–small cell lung cancer, breast cancer, cervical carcinoma, Kaposi’s sarcoma
Antibiotics
bleomycin	IM, IV, subcutaneous: 0.25-0.5 units/kg once or twice weekly	Nausea, vomiting, fever, very toxic	Edema of hands, pulmonary fibrosis, stomatitis, alopecia	Hodgkin’s disease, non-Hodgkin’s lymphoma, squamous cell carcinoma of head and neck, testicular carcinoma
dactinomycin (Actinomycin D; Cosmegen)	Highly variable for condition being treated	Nausea, vomiting, local irritant	Stomatitis, oral ulcers, diarrhea, alopecia, mental depression, bone marrow depression	Testicular carcinoma, Wilms’ tumor, rhabdomyosarcoma, Ewing’s and osteogenic sarcoma, and other solid tumors
daunorubicin (Cerubidine)	IV: 30-45 mg/m2/day for 2-3 days of combination therapy Never give IM or subcutaneously	Nausea, vomiting, diarrhea, fever, chills	Bone marrow suppression, reversible alopecia	Acute nonlymphocytic leukemia in adults; acute lymphocytic leukemia in children and adults
doxorubicin HCl, conventional (Adriamycin) Do not confuse Adriamycin with Aredia. Do not confuse doxorubicin HCl, conventional with doxorubicin HCl, liposomal.	IV: 60-75 mg/m2, single dose or over 3 days; repeat q 3 wk up to total dose 500 mg/m2	Nausea, red urine (not hematuria)	Bone marrow depression, cardiotoxicity, alopecia, stomatitis	Soft tissue, osteogenic and miscellaneous sarcomas, Hodgkin’s disease, non-Hodgkin’s lymphoma, bronchogenic and breast carcinoma, thyroid cancer, leukemias
epirubicin (Ellence)	IV: 100 to 120 mg/m2 once q 3- to 4-wk cycle	Nausea, vomiting, red urine (not hematuria), rash, diarrhea	Bone marrow depression, cardiotoxicity, alopecia, stomatitis	Breast cancer
idarubicin (Idamycin)	Slow IV: 12 mg/m2/day (10-15 min) for 3 days Never give IM or subcutaneously	Nausea, vomiting, diarrhea	Bone marrow suppression, cardiotoxicity, mucositis, hemorrhage	Acute myeloid leukemia
mitomycin C (MTC, Mutamycin)	Variable	Nausea, vomiting, flu-like syndrome	Bone marrow depression, skin toxicity; pulmonary, renal, CNS effects	Squamous cell carcinoma of cervix; adenocarcinoma of the stomach, pancreas, bladder cancer
mitoxantrone (Novantrone)	IV infusion: 12 mg on days 1 to 3, q 3 wk or q 3 mo	Nausea, vomiting, diarrhea	Heart failure; GI bleeding; cough, dyspnea	Acute nonlymphocytic leukemia, prostate cancer
valrubicin (Valstar)	800 mg q wk via urethral catheter into bladder	Bladder spasm, hematuria, abdominal pain	Rash	Carcinoma in situ of the urinary bladder
Other Synthetic Agents
aldesleukin (Proleukin) Do not confuse aldesleukin with Oprelvekin.	Variable	Confusion, dyspnea, nausea, diarrhea	Bone marrow depression, liver dysfunction	Melanoma, renal cell carcinoma, T-cell lymphoma
altretamine (Hexalen)	PO: 260 mg/m2/day for 14 or 21 days in 28-day cycle Give daily dosage as four divided oral doses	Nausea, vomiting	Anemia, leukopenia, thrombocytopenia, peripheral neuropathy	Ovarian cancer
degarelix (Firmagon)	Subcutaneous: 240 mg as two injections of 120 mg at a concentration of 40 mg/mL; then 80 mg subcutaneously q 28 days	Chills, fatigue	Weight increase, back pain; injection site injury (pain, erythema, swelling)	Advanced prostate cancer
denileukin diftitox (Ontak)	IV: 9 or 18 mcg/kg/day for 5 consecutive days; q 21 days for eight cycles	Hypotension, dysrhythmias, dizziness, anorexia, nausea, vomiting	Vascular leak syndrome manifested by hypotension, edema, hypoalbuminemia; anemia, paresthesias	Cutaneous T-cell lymphoma
hydroxyurea (Hydrea) Do not confuse hydroxyurea with hydroxyzine.	PO: 80 mg/kg as a single dose q 3 days or 20-30 mg/kg/day	Mild nausea, vomiting	Bone marrow depression	Chronic granulocytic leukemia, ovarian cancer, melanoma, carcinoma of the head and neck
interferon alfa-2b (Intron A)	Variable	Flulike syndrome	Bone marrow depression	Hairy cell leukemia, Kaposi’s sarcoma, malignant melanoma, follicular lymphoma, hairy cell leukemia
leuprolide acetate (Lupron, Lupron Depot)	Subcutaneous: 1 mg daily IM, depot dosing range: 3.75-4.5 mg q 1-6 mo	Hot flashes; initial exacerbation of symptoms	Dysrhythmias, edema	Prostatic carcinoma, breast carcinoma; endometriosis
mitotane (Lysodren)	2-6 g/day in three or four divided doses, then increase incrementally to 9-10 g/day in three or four divided doses (maximum daily dose 18 g)	Nausea, vomiting	Dermatitis, diarrhea, mental depression	Adrenal cortical carcinoma
procarbazine hydrochloride (Matulane)	Single agent treatment for Hodgkin’s disease: PO: start 2-4 mg/kg/day for the first week; increase over 1 wk to 4-6 mg/kg as maintenance until maximum response or hematological toxicity	Nausea, vomiting	Bone marrow depression, CNS depression	Hodgkin’s disease, non-Hodgkin’s lymphoma, lung cancer, melanoma
sipuleucel-T (Provenge)	IV: three complete doses at 2-wk intervals	Fatigue, chills, headache, fever, nausea, vomiting	Paresthesias, back pain, joint ache, pain in extremities	Prostate cancer
Hormones
anastrozole (Arimidex) Do not confuse Arimidex with Aranesp or Aricept.	PO: 1 mg daily	Nausea, vomiting, headache	Hot flashes, diarrhea, constipation, pelvic pain, edema	Breast cancer in postmenopausal women with disease progression following tamoxifen therapy
bicalutamide (Casodex)	PO: 50 mg daily (use with luteinizing hormone–releasing hormone [LHRH] analog)	Nausea, constipation, peripheral edema, diarrhea	Hepatitis, gynecomastia, dyspnea	Prostate cancer
estramustine (Emcyt)	14 mg/kg/day in three or four divided doses Take with water No calcium-rich products	Nausea, diarrhea	Thrombosis, hyperglycemia, hepatic dysfunction, breast tenderness	Prostate cancer
ethinyl estradiol	Prostate: PO: 1-2 mg three times daily Breast: PO: 10 mg three times daily	None	Fluid retention, hypercalcemia, feminization, uterine bleeding	Breast and prostate carcinomas
exemestane (Aromasin)	25 mg daily after a meal	Nausea, fatigue, insomnia	Depression, anxiety, hot flashes, dyspnea	Breast cancer in postmenopausal women, with disease progression following tamoxifen therapy
fluoxymesterone (Androxy)	PO: 10-40 mg/day in divided doses	None	Fluid retention, masculinization, cholestatic jaundice	Breast carcinoma
flutamide (Eulexin)	PO: 250 mg three times daily at 8-hr intervals (total daily dose is 750 mg)	Nausea, vomiting	Hot flashes, loss of libido, impotence, gynecomastia, hepatotoxicity	Metastatic prostatic carcinoma
fulvestrant (Faslodex)	IM: 500 mg in buttocks (one 250 mg injection in each buttock) on days 1, 15, 29, and then once monthly thereafter	Nausea, headache, constipation	Dyspnea, rash	Breast cancer
goserelin (Zoladex)	Subcutaneous implant: 3.6 mg q 28 days in upper abdominal wall Local anesthesia may be used	Anorexia, dizziness, pain	Hot flashes, sexual dysfunction	Prostate and breast cancer
histrelin (Vantas)	Subcutaneous implant: 50 mg in inner aspect of upper arm q 12 mo	Insertion site reaction	Hot flashes, gynecomastia, fatigue	Prostate cancer
letrozole (Femara)	PO: 2.5 mg daily	Nausea, vomiting, headache	Muscle aches, hot flashes, constipation, diarrhea, fatigue	Breast cancer in postmenopausal women with disease progression following antiestrogen therapy
medroxyprogesterone acetate	IM: 400-1000 mg/wk	None	None	Endometrial carcinoma, renal cell, breast cancer
nilutamide (Nilandron)	PO: 300 mg once daily for 30 days, then 150 mg daily	Insomnia, headache, nausea, constipation	Hot flashes, impaired adaptation to dark	Prostate cancer
tamoxifen Do not confuse tamoxifen with Tamiflu or tamsulosin.	20-40 mg daily in two divided doses	Nausea, vomiting, hot flashes	Increased bone and tumor pain, thrombocytopenia, leukopenia, edema, hypercalcemia	Breast cancer (estrogen sensitive)
testosterone enanthate (Delatestryl)	IM: 200-400 mg q 2-4 wk	None	Fluid retention, masculinization	Breast carcinoma
toremifene (Fareston)	PO: 60 mg daily	Nausea, vomiting	Hot flashes, sweating, vaginal discharge	Metastatic breast cancer in postmenopausal women with estrogen-positive tumors
triptorelin (Trelstar Depot)	Depot: 3.75 mg IM: q 28 days	Vomiting, fatigue	Hot flashes, impotence, insomnia	Prostate cancer
triptorelin (Telstar LA)	IM: Long-impacting: 11.25 mg q 84 days, or 22.5 mg q 24 wk	Vomiting, fatigue	Hot flashes, impotence, insomnia	Prostate cancer
DNA Topoisomerase Inhibitors
irinotecan (Camptosar)	Variable depending on regimen	Nausea, vomiting, anorexia, diarrhea, constipation, shortness of breath	Diarrhea, bone marrow suppression, alopecia	Carcinoma of the colon and rectum
topotecan (Hycamtin)	IV: 2.3 mg/m2 over 30 min for 5 days of a 21-day course	Nausea, vomiting, diarrhea, shortness of breath	Alopecia, bone marrow depression, stomatitis	Small cell lung cancer

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