BRS Pharmacology - Chapter 12 Cancer Chemotherapy
A 74-year-old man with a 100-pack/year history of smoking is evaluated for hemoptysis. A computed tomography (CT) scan of the chest shows numerous pulmonary nodules. A nodule on the pleural surface is selected for CT-guided biopsy by the interventional radiologist. The biopsy report is small-cell carcinoma of the lung, and chemotherapy containing etoposide is started. This drug works by (A) Inhibiting topoisomerase II (B) Inhibiting dihydrofolate reductase (C) Alkylating double-stranded DNA (D) Stabilizing microtubules, with resultant mitotic arrest (E) Causing DNA chain scission and fragmentation
The answer is (A) Inhibiting topoisomerase II. Etoposide is used in the treatment of small-cell lung carcinomas as well as testicular tumors. Its mechanism of action is related to its ability to inhibit topoisomerase II. Methotrexate inhibits dihydrofolate reductase. Alkylating agents include mechlorethamine, cyclophosphamide, and ifosfamide. Paclitaxel and docetaxel stabilize microtubules and thereby disrupt mitosis. Bleomycin causes DNA chain scission and fragmentation.
A 42-year-old premenopausal woman recently underwent partial mastectomy and radiation therapy for a small tumor in her breast. There were no lymph nodes involved, and the tumor was estrogen-receptor positive. The oncologist explains that there is a little advantage to adding systemic chemotherapy in such an early-stage cancer but does recommend that the patient take tamoxifen. Which of the following is a concerning side effect of tamoxifen? (A) Thromboembolism (B) Bowel perforation (C) Aplastic anemia (D) Myelosuppression (E) Hypotension
The answer is (A) Thromboembolism. Patients with estrogen receptor-positive tumors benefit from tamoxifen adjunct treatment. It, however, carries a risk of thromboembolism as well as the potential to develop endometrial cancer. Bevacizumab has been associated with the risk of bowel perforation. Many traditional chemotherapeutic agents are associated with myelosuppression, and in fact, that is the mechanism for the effects against leukemias. The antibiotic chloramphenicol has been associated with both myelosuppression and aplastic anemia. Many of the therapeutic monoclonal antibodies can cause infusional hypotension.
A 53-year-old man presents with changes in bowel frequency and pencil-thin stools with occasional bright red blood in the stool. A further work-up, including computed tomography (CT) scanning of the chest, abdomen, and pelvis, demonstrates lesions consistent with metastasis in the liver. His therapy will likely include which of the following chemotherapeutic agents? (A) Carmustine (B) 5-Fluorouracil (C) Leuprolide (D) Temozolamide (E) Tamoxifen
The answer is (B) 5-Fluorouracil. 5-Fluorouracil is an important agent in cases of metastatic colon cancer and is part of the FOLFOX regimen. Carmustine is used in the treatment of brain tumors, as is temozolomide. Leuprolide is used to treat hormone-sensitive prostate cancer, and tamoxifen is used to treat breast cancer.
A 73-year-old woman with breast cancer and history of congestive heart failure is placed on a chemotherapy regimen that includes the use of methotrexate (MTX) after her mastectomy. This agent's activity is related to its ability to do what? (A) Carbamylate intracellular macromolecules (B) Indirectly inhibit DNA synthesis (C) Block chromosomal migration and cell differentiation (D) Complex with DNA to form crosslinks (E) Inhibit estrogen-dependent tumor growth
The answer is (B) Indirectly inhibit DNA synthesis. Methotrexate inhibits the enzyme dihydrofolate reductase, which ultimately decreases the availability of thymidylate to produce DNA. Nitrosoureas can carbamylate intracellular molecules. Vinca alkaloids such as vinblastine block chromosomal migration and cellular differentiation. Cisplatin works primarily by complexing with DNA to form crosslinks. Agents like tamoxifen inhibit estrogen-dependent tumor growth.
A 63-year-old African-American man with a history of prostate cancer had his prostate removed 10 years ago. His prostatespecific antigen levels have begun to rise again, and he complains of back pain, suggesting metastatic disease. A computed tomography (CT) scan demonstrates enlarged para-aortic lymph nodes and osteoblastic lesions of his lumbar spine. Therapy with which agent should be started? (A) Anastrozole (B) Leuprolide (C) Tamoxifen (D) Mitotane (E) Prednisone
The answer is (B) Leuprolide. Leuprolide is used to treat metastatic prostate cancer by decreasing the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary, leading to decreased testosterone, used by the tumor cells to grow. Anastrozole is used in breast cancer in postmenopausal women to decrease the estrogen levels. Tamoxifen is also used in the treatment of breast cancer to inhibit estrogen-mediated gene transcription. Mitotane is used in the treatment of inoperable adrenocortical carcinomas. Prednisone is used in the treatment of leukemias and lymphomas.
A 35-year-old otherwise healthy man presents with fullness in the inguinal region with swelling of the ipsilateral leg. A computed tomography (CT) scan demonstrates several confluent enlarged lymph nodes. Biopsy specimens demonstrate malignant CD201 B cells. A diagnosis of diffuse B-cell lymphoma is made. Which of the following biologics will likely be given to the patient? (A) Traztuzumab (B) Rituxaimab (C) Dactinomycin (D) l-Asparaginase (E) Interferon-α
The answer is (B) Rituxaimab. Rituximab is used in conjunction with cyclophosphamide, hydroxydaunomycin (doxorubicin), vincristine, and prednisone (R-HOP), one of the regimens for non-Hodgkin lymphoma. Traztuzumab is used for HER21 breast cancer. Dactinomycin is a protein synthesis inhibitor used to treat such pediatric tumors as rhabdomyosarcoma and Wilms tumor. L-Asparaginase is a recombinant enzyme used to treat leukemias. Lastly, interferon-α can be used to treat hairy cell leukemia.
A 63-year-old postmenopausal woman is diagnosed with early stage breast cancer, which is initially managed by partial mastectomy and radiation therapy. Her tumor was positive for expression of estrogen receptors. Which agent would you recommend to this patient to prevent relapse? (A) Leuprolide (B) Hydroxyurea (C) Anastrozole (D) Carboplatin (E) Goserelin
The answer is (C) Anastrozole. Anastrozole is an aromatase inhibitor used to inhibit estrogen synthesis in the adrenal gland, a principle source in postmenopausal women. Hydroxyurea is used in the treatment of some leukemias as well as myeloproliferative disorders. Leuprolide and goserelin are GNRH antagonists used to treat prostate cancer. Carboplatin is used in the treatment of ovarian cancers and others.
A 37-year-old man presents with changes in bowel habits for the last several months. He complains of small stool caliber along with occasional blood in his stools. Colonoscopy reveals the diagnosis of colon adenocarcinoma. Further work-up demonstrates that there are metastatic lesions in his liver. The oncologist recommends the use of bevacizumab. This agent (A) Inhibits cell cycle progression (B) Induces differentiation of cells (C) Blocks signaling by vascular EGF (D) Inhibits angiogenesis (E) Inhibits HER2/neu signaling
The answer is (C) Blocks signaling by vascular EGF. Bevacizumab is a monoclonal antibody against vascular endothelial growth factor (VEGF) interaction with its receptor. Trastuzumab is also a monoclonal antibody, but it inhibits HER2/neu signaling.
A 56-year-old man complains of fatigue and malaise. On physical examination he has significant splenomegaly. His white blood cell count is dramatically elevated, and the physician suspects leukemia. Chromosomal studies indicate a (9:22) translocation, the Philadelphia chromosome, confirming the diagnosis of chronic myelocytic leukemia (CML). Which of the following might be used in his treatment? (A) Anastrozole (B) Rituximab (C) Imatinib (D) Gefitinib (E) Amifostine
The answer is (C) Imatinib. Imatinib is an orally active small molecule inhibitor of the oncogenic Bcr-Abl kinase produced as a result of the Philadelphia chromosome, sed to treat CML. It also inhibits the c-Kit receptor and can be used in GI stromal tumors (GISTs). Anastrozole is used in the management of breast cancer. Rituximab is an antibody used in the treatment of non-Hodgkin lymphoma. Gefitinib is an orally active small-molecule inhibitor of the EGF receptor used in the treatment of some lung cancers. Amifostine is used as a radioprotectant with or without cisplatin.
A second-year medical student finds a few hours a week to work in a cancer research laboratory. Her project involves testing various hemotherapy agents (including adriamycin and etoposide) on colon cancer lines established from patient biopsies. She performs Northern blot analysis on multiply resistant cell lines and is likely to find increased expression of what gene? (A) Bcr-Abl (B) EGFR (C) MDR (D) HER2 (E) HGPRT
The answer is (C) MDR. Gene amplification of the multidrug resistance (MDR1) gene is found in many tumors and confers resistance to many chemotherapy agents. MDR1 encodes a transport protein that actively pumps various chemotherapy agents out of the cell. Although Bcr-Abl, EGFR, and HER2 may be overexpressed in tumors, they don't necessarily confer resistance to chemotherapy. HGPRT is overexpressed in some tumors, but it only confers resistance to methotrexate.
A world-class cyclist was diagnosed with metastatic testicular cancer with lesions in both his lung and brain. He forgoes the standard treatment for his condition because he learns one of the drugs typically used for his condition could ultimately compromise his pulmonary function. Which of the following is included in the standard regimen and is associated with his feared complication? (A) Cisplatin (B) Busulfan (C) Aminoglutethimide (D) Bleomycin (E) Cyclophosphamide
The answer is (D) Bleomycin Bleomycin is included in the treatment of metastatic testicular neoplasms and can cause pulmonary fibrosis. Busulfan can also cause pulmonary fibrosis; however, it is not used in the treatment of testicular neoplasms. Cisplatin is highly emetogenic and can cause nephrotoxicity as well as ototoxicity. Aminoglutethimide is an inhibitor of steroid synthesis used in Cushing syndrome as well as in some cases of breast cancer. Cyclophosphamide can cause hemorrhagic cystitis.
A 54-year-old woman complains of headache, nausea, and vomiting. A computed tomography (CT) scan of the head reveals a large mass in the frontal lobe. She underwent surgery to remove the mass, which was shown to be a glioblastoma multiforme (GBM). In addition to receiving radiation, which agent should be given? (A) Thalidomide (B) Cisplatin (C) Thioguanine (D) Temozolomide (E) Mercaptopurine
The answer is (D) Temozolomide. Temozolomide is an orally active alkylating agent related to dacarbazine', which is used along with radiation for the treatment of glioblastoma multiforme and other high-grade astrocytomas. Thalidomide is used in the treatment of multiple myeloma. Thioguanine and mercaptopurine are purine analogs that are used primarily in acute lymphoblastic leukemia. Cisplatin is also often used with radiation in tumors of the lung, head, and neck.
A 17-year-old girl sees her physician for swollen lymph nodes in the supraclavicular region. A core biopsy demonstrates Reed-Sternberg cells and fibrotic bands, a finding characteristic of nodular sclerosis Hodgkin disease. Which of the following combined regimens might be used in this patient? (A) R-CHOP (B) CMF (C) FOLFOX (D) BEP (E) ABVD
The answer is (E) ABVD. ABVD is a treatment regimen used for Hodgkin disease and includes adriamycin, bleomycin, vinblastine, and dacarbazine. R-CHOP is used or treating nonHodgkin's disease. CMF, or cyclophosphamide, methotrexate, and fluorouracil, is used for breast cancer. FOLFOX, a regimen that uses 5-fluorouracil, oxaliplatin, and leucovorin, is used in the treatment of colon cancer. BEP (bleomycin, etoposide, and platinum [cisplatin]) is used in the management of metastatic testicular neoplasms.
7. A 56-year-old woman with metastatic breast cancer is started on chemotherapy. Her initial treatment will include both cyclophosphamide and doxorubicin. Careful attention is required because of doxorubicin's well-documented toxicity, which is (A) Hemorrhagic cystitis (B) Acne (C) Peripheral neuropathy (D) Hot flashes (E) Cardiomyopathy
The answer is (E) Cardiomyopathy. Doxorubicin is associated with dose-limiting cardiomyopathy. Before using this agent, a thorough cardiac evaluation is required, including an echocardiogram or nuclear medicine scan of the heart. Hemorrhagic cystitis is a complication of cyclophosphamide, prevented by co-administration of MESNA. Acne is a side effect of prednisone and EGFR inhibitors. Peripheral neuropathy is a result of taxanes such as paclitaxel. Hot flashes often accompany tamoxifen use.
A 56-year-old woman with a significant smoking history was diagnosed with small-cell lung cancer 2 years ago and was successfully treated. Now on follow-up computed tomography (CT) scan, there are several new pulmonary nodules, and the oncologist elects to begin second-line chemotherapy with a DNA topoisomerase I inhibitor. Which of the following is such an agent? (A) Ciprofloxacin (B) Etoposide (C) Vinorelbine (D) Teniposide (E) Irinotecan
The answer is (E) Irinotecan. Irinotecan and topotecan are two antineoplastic agents that inhibit DNA topoisomerase I. Etoposide and teniposide are epipodophyllotoxins that inhibit DNAtopoisomerase II. Ciprofloxacin is an antibiotic that inhibits bacterial DNA topoisomerase I. Vinorelbine is a vinca alkaloid that disrupts microtubule assembly.
A 53-year-old woman with breast cancer undergoes a breast-conserving lumpectomy and lymph node biopsy. The pathology report returns with mention of cancer cells in two of eight lymph nodes removed. Following radiation therapy, chemotherapy is started hat includes the use of paclitaxel. Which side effect is the patient likely to complain of? (A) Blood in the urine (B) Easy bruising (C) Hot flashes (D) Shortness of breath (E) Numbness and tingling
The answer is (E) Numbness and tingling. Paclitaxel is often used in the treatment of breast as well as ovarian and lung cancer. Its main toxicities are myelosuppression and peripheral neuropathy that usually manifest as numbness and tingling in the distal extremities. Blood in the urine can indicate hemorrhagic cystitis, a complication of cyclophosphamide use. Easy bruising can result from mechlorethamine use. Hot flashes are a common complaint in patients using tamoxifen. Shortness of breath can result from pulmonary fibrosis secondary to busulfan or bleomycin use.
A 25-year-old man presents with recurrent bouts of hypoglycemia with mental status changes that are rapidly reversed by eating. He is not diabetic, and his serum levels of insulin are markedly elevated. His C-peptide levels are also elevated. You begin treating the patient for a presumed insulinoma with which of the following agents? (A) Cyclophosphamide (B) Melphalan (C) Carmustine (D) Thiotepa (E) Streptozocin
The answer is (E) Streptozocin. Streptozocin is toxic to β cells of the islets of Langerhans in the pancreas and is therefore used in the treatment of insulinomas. Melphalan is a derivative of nitrogen mustard used to treat multiple myeloma, melanoma, and carcinoma of the ovary. Carmustine is a drug used to treat neoplasms of the brain, as it has excellent central nervous system (CNS) penetration. Thiotepa is used in the treatment of bladder cancer.
