Antiangiogenic Agents: Changing the Nature of Cancer Treatment   
DiaLog: Angiogenesis Research: Looking for New Ways to Measure Success, by Roy S. Herbst, MD, PhD, Assistant Professor, Department of Thoracic/Head and Neck Medical Oncology   
House Call: Overcome Fears of Cancer Recurrence by Taking Action   
Recognition Spurs Prevention of Osteoporosis in Patients with Cancer   
Protocols: Clinical Trials of Antiangiogenic Agentshttps://openworks.mdanderson.org/oncolog/1097/thumbnail.jp

Herbst, Roy S., MD, PhD

O\u27Suilleabhain, Kate

Wright, Kerry L.

English

Antiangiogenic Agents: Changing the Nature of Cancer Treatment DiaLog: Angiogenesis Research: Looking for New Ways to Measure Success, by Roy S. Herbst, MD, PhD, Assistant Professor, Department of Thoracic/Head and Neck Medical Oncology House Call: Overcome Fears of Cancer Recurrence by Taking Action Recognition Spurs Prevention of Osteoporosis in Patients with Cancer Protocols: Clinical Trials of Antiangiogenic Agentshttps://openworks.mdanderson.org/oncolog/1097/thumbnail.jp

OpenWorks @ MD Anderson

University of Texas MD Anderson Cancer Center OpenWorks @ MD Anderson OncoLog MD Anderson's Report to Physicians (All issues) OncoLog MD Anderson's Report to Physicians 5-2001 OncoLog Volume 46, Number 05, May 2001 Kate O'Suilleabhain Roy S. Herbst MD, PhD Kerry L. Wright Follow this and additional works at: https://openworks.mdanderson.org/oncolog  Part of the History of Science, Technology, and Medicine Commons, and the Oncology Commons                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             at maximum tolerated doses are ineffec­tive in combating cancer. In a preclini­cal study of interferon, Dr. Fidler found that the optimal biologic dose-the drug level at which the surrogate markers of disease were lowest-was only one tenth the maximum tolerated dose. "As you increase the dose toward tolerance, the markers become elevated because the cells no longer respond to interferon," he said. In fact, the cells reach a state of tolerance that destroys the very signaling cascade on which the efficacy of these drugs depends. Because the relationship between dosage and efficacy is nonlinear and because these agents are, at least in the short term, nontoxic, future trials should attempt to identify the optimal biologic doses rather than the maximum tolerated doses. Mose antiangiogenic agents are still in the early stages of clinical assessment, but the results so far suggest that these drugs cause disease stabilization, rather than regression, in humans. A reduction in the time to disease progression has been an important finding, since it proves that the drugs render tumor cells incapable of growth. Nevertheless, it is somewhat disappointing that patients did not show the marked tumor shrink­age seen earlier in laboratory mice. "We have to lower our goals in cancer treatment," said Lee Ellis, M.D., an cancer following treatment with interleukin-2 (1099-291). Physician: Christopher J. Logothetis, M.D. • Multicenter, open-ended, double-blind, placebo-controlled phase Illstudy of AE-941 in addition tocombined-modality treatment (che-motherapy and radiation therapy) forlocally advanced unresectable non-small cell lung cancer (1099-303).Physician: Charles Lu, M.D.• Phase I trial of thalidomide formultiple myeloma (DM98-359).Physician: Donna M. Weber, M.D.• A phase I dose-escalation andpharmacokinetic evaluation of oralLY317615 in patients with advancedcancer (ID00-382). Physician: RoyHerbst, M.D., Ph.D.Dr. Roy Herbst, right, an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology, examines patient with the help of Mercedes Guerra, an advanced practice nurse. Dr. Herbst is the principal investigawr of several trials of antiangiogenic agents, most notably endostatin.associate professor in the Department of Surgical Oncology. "We need to slow growth of tumors to a point where patients can live with their disease as a chronic condition." By slowing or stopping tumor growth and metastasis, angiogenesis inhibitors could provide the fLrst "maintenance therapy" for solid tumors. Angiogenesis inhibitors might also prove effective in preventing disease in patients at high risk for various malignancies. In addi-PROTOCOLS • A tolerance and efficacy trial of preoperative thalidomide treatmentfollowed by radical retropubic pros-tatectomy in select patients withlocally advanced prostate cancer(1000-089). Physician: Danai Daliani,M.D.• A phase II trial of thalidomide-dexamethasone for multiple myeloma(ID00-070). Physician: Donna M.Weber,M.D.• Phase II study of gemcitabine-basedchemoradiation and TNP-470 forpatients with locally advanced,nonmetastatic adenocarcinoma ofthe pancreas (ID98-248). Physician:Douglas 8. Evans, M.D.• Phase 1/11 study of paclitaxel,estramustine phosphate, andthalidomide for patients with meta-tion, they might be useful in early-stage cancers to prevent disease recurrence among patients who have undergone surgical resection of the primary tumor. Eventually, clinicians hope to combine antiangiogenic agents with chemo­therapy to stave off tumor progression. Researchers have also begun to explore the synergism between antiangiogenic agents in the laboratory. When adminis­tered co mice, the combination of (Continued on page 4) static androgen-independent prostate carcinoma (ID00-087). Physician: Danai Daliani, M.D. • A phase I, single-center, open-label,dose-escalation, safety, and pharma­cokinetic study of recombinanthuman endostatin administered bycontinuous intravenous infusion topatients with cancer (1001-074).Physician: Roy Herbst, M.D., Ph.D.•FoA MORE INFORMATION about these clinical trials, physicians or patients may call the M. D. Anderson lnfatmation Line. Thosewithin the United States should call (800)392-1611; those in Houston or outside theUnited States should call (713) 792-6161.Visit the M. D. Anderson CancerCenter clinical trials Web site at httf)://www. cUnicaltrials. org for a broader listingof treatment research protocols.OncoLog / 3 rs Prevention of Patients with Cancer bone resorption. For instance, long-term use of such glucocorticoids as pred­nisone and cortisone, which are often used to treat patients with leukemias and lymphomas, can cause even further bone loss. Steroids, along with cranial irradia­tion, can also cause growth hormone deficiencies. According to Dr. Sellin, most bone development occurs by the age of 25, so once many survivors of childhood cancers reach adulthood, they are at increased risk for osteo, porosis, not because their bones have deteriorated but because they have not accumulated normal bone masses. Another group of at-risk patients are those treated for hormone-responsive cancers. Prostate cancer, for example, is commonly treated with orchiectomy (excision of one or both of the testes) or with the antineoplastic agent leuprolide (Lupron), both of which cause androgen ablation or deficiency. Similarly, women with breast cancer who develop early ------: menopause are at increased risk of developing osteoporosis. According to the National Osteoporosis Foundation (NOF), women often lose up to 20% of their bone mass in the five to seven years after menopause, and for some women with breast cancer, this loss of bone mass can begin up to 10 years earlier than normal. Furthermore, chemotherapy and radiation therapy (not necessarily associated with breast and prostate cancers) can cause gonadal damage, which may also cause a loss of estrogen or testosterone. "Since estrogen or testosterone deficiency leads to bone loss," said Dr. Sellin, "prompt and careful replacement is important for these patients." Hormone-replacement therapy with estrogen, estrogen and progestin, or testosterone can be used to prevent and treat osteoporosis in many of these individuals, although estrogen-replace­ment therapy is contraindicated in patients with breast cancer. For those patients, other drugs are avail­able, such as raloxifene (Evista), a selective estrogen receptor modulator approved by the Food and Drug Administration (FDA) to both prevent and treat osteo­porosis. Similarly, tamoxifen, which is often used as adjuvant therapy after breast cancer, has also been found to protect against bone loss in postrneno­pausal women. Dr. Rena Sellin, left, a professor in the Depart­ment of Endocrine Neoplasia and Hormonal Disorders, discusses osteoporosis prevention with a patient in rhe clinic. Another FDA-approved drug for preventing and treating osteoporosis is alendronate (Fosamax), a bisphosphonate, or agent that inhibits bone resorption at sites of osteoid mineralization. According to the NOF, this drug is often indicated specifically for the treatment of steroid-induced osteoporosis. Calcitonin (Miacalcin), a naturally occur­ring hormone that is important for calcium regulation and bone metabolism, has also been approved in the form of a nasal spray to creat osteoporosis, "Since estrogen or testosterone deficiency leads to bone loss, prompt and careful replacement is important." - Rena Sellin, M.D., professor,Department of EndocrineNeoplasia and Hormonal Disorders mainly in postmenopausal women. According to Dr. Sellin, all of these agents work by inhibiting the activity of osteoclasts. While many of them have also been shown to increase bone density, they work primarily by inhibit­ing bone resorption so that normal bone formation can occur more quickly. "For the most part, agents that are used in patients with cancer to treat osteoporosis are similar to the agents that are used in other patients," said Dr. Sellin. The biggest difference is that patients with cancer have certain contraindications that limit the number of drugs they can choose from. Aside from medications, a healthy lifestyle can be the biggest key to preventing osteoporosis and the hip, spine, and wrist fractures commonly associated with reduced bone mass. Quitting smoking, increasing calcium intake, limiting alcohol consumption, treating metabolic and endocrine disorders, and exercising can all contrib­ute. While weight-bearing exercises have been shown to improve muscle mass ( which protects bones), in many instances they also result in fractures in individuals whose bones are already weak. According to Dr. Sellin, a healthy alternative is to exercise in the water. "Exercising in water allows patients who have feeble skeletons to stretch and increase muscle tone and muscle mass without putting their bones at risk," Dr. Sellin said. Beyond that, Dr. Sellin advises patients to use common sense in their daily activities, including wearing shoes with nonslip soles and abstaining from activities that could increase the risk of falling.• FOR MORE INFORMATION, contaet Dr. Sellin at (713) 792�2841. OncoLog / 5                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    

OncoLog, Volume 46, Number 05, May 2001

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OncoLog Volume 46, Number 05, May 2001

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