ONCOLOGY Vol 19 No 5

Many elderly individuals have substantial life expectancy, even inthe setting of significant illness. There is evidence to indicate that elderlyindividuals derive as much survival benefit as younger patientsfrom standard chemotherapy approaches in advanced colorectal cancer.Effective treatments should not be withheld from older patients onthe basis of age alone. Treatment decisions should be based on functionalstatus, presence of comorbidities, and consideration of drug-specifictoxicities that can be exacerbated in older individuals due to decreasedfunctional reserve. Infusional and weekly fluorouracil (5-FU)regimens are better tolerated than bolus and monthly regimens. Oralcapecitabine (Xeloda) reduces the frequency of a number of toxicitiescompared with bolus 5-FU, including stomatitis, a particularly debilitatingtoxicity in many elderly patients. The effectiveness and tolerabilityof oxaliplatin and irinotecan (Camptosar) appear to be similar inolder and younger patients. Older patients can also receive bevacizumab(Avastin), although caution is warranted in those with cardiovasculardisease. Overall survival in metastatic colorectal cancer improves withthe availability of multiple effective chemotherapeutic agents. The fullrange of effective therapies in advanced colorectal cancer should beextended to elderly patients.

Targeted therapies offer a new approach to breast cancer treatment.Rather than eliminating both malignant and normal cellsnonspecifically, these so-called “rational” therapies exploit second messengerproteins, ligands, and receptors that are known to be upregulatedin neoplastic cells, or are implicated in cancer metastasis. This reviewwill highlight a number of these targets and the mechanisms that havebeen targeted in drug design. We will also describe recently completedand currently ongoing clinical trials investigating targeted therapiesand their potential to augment standard breast cancer therapy.

Androgen-deprivation therapy, usually with combined androgenblockade, is standard initial treatment for advanced prostate cancer.With failure of initial treatment, as indicated by rising prostate-specificantigen (PSA) levels, second-line hormonal therapy is usually instituted.Over the past several years, it has become increasingly clear thatsystemic chemotherapy has an important role in hormone-refractorydisease. Phase II trials have demonstrated high PSA and measurabledisease response rates with taxane single-agent and combination treatments.One recent phase III trial showed that docetaxel (Taxotere)/estramustine (Emcyt) significantly improved overall survival, progression-free survival, and PSA response rate compared with mitoxantrone(Novantrone) plus prednisone. Another phase III trial demonstratedthat docetaxel given every 3 weeks plus prednisone significantly improvedoverall survival, PSA response rate, pain relief response rate,and quality of life compared with mitoxantrone and prednisone. Onthe basis of these findings, every-3-week docetaxel plus prednisone isnow considered standard first-line therapy for metastatic hormonerefractorydisease. There is considerable optimism that treatment canbe further improved. Studies of taxane combinations with bevacizumab(Avastin), thalidomide (Thalomid), bortezomib (Velcade), antisenseBcl-2 oligonucleotide, mTOR inhibitors, epidermal growth factor receptorinhibitors, and KDR inhibitors are under way. Randomized phaseIII trials in progress or planned are examining docetaxel in combinationwith imatinib mesylate (Gleevec) or calcitriol and docetaxel/prednisonein combination with bevacizumab and an antisense clusterincompound. Other promising systemic agents include epothilones andatrasentan, and promising vaccines include Provenge, GVAX, andProstvac.

Significant advances have been made in the treatment of advancedcolorectal cancer over the past 5 years, namely due to the introductionof three novel cytotoxic agents-capecitabine (Xeloda), irinotecan(Camptosar), and oxaliplatin (Eloxatin)-and the recent approval oftwo biologic agents-bevacizumab (Avastin) and cetuximab (Erbitux).During this time period, the median survival of patients with advanced,metastatic disease has gone from 10 to 12 months to nearly 24 months.Intense efforts have focused on identifying novel targeted therapies thattarget specific growth factor receptors, critical signal transduction pathways,and/or key pathways that mediate the process of angiogenesis.Recent clinical trial results suggest that the anti-VEGF antibodybevacizumab can be safely and effectively used in combination witheach of the active anticancer agents used in colorectal cancer. Despitethe development of active combination regimens, significant improvementsin the actual cure rate have not yet been achieved. Combinationregimens with activity in advanced disease are being evaluated in theadjuvant and neoadjuvant settings. The goal is to integrate these targetedstrategies into standard chemotherapy regimens so as to advancethe therapeutic options for the treatment of advanced colorectal cancer.Finally, intense efforts are attempting to identify the critical molecularbiomarkers that can be used to predict for either clinicalresponse to chemotherapy and/or targeted therapies and/or the drugspecificside effects. The goal of such studies is to facilitate the evolutionof empiric chemotherapy to individually tailored treatments forpatients with colorectal cancer.

Standard therapy for multiple myeloma, which accounts for 10% ofall hematologic malignancies, has been autologous stem cell transplantation(ASCT), alkylator-based chemotherapy, and corticosteroids. Severaladvances have been made in the treatment of multiple myelomaover the past decade, especially the arrival of new, active agents suchas thalidomide (Thalomid), bortezomib (Velcade), and lenalidomide(Revlimid). These have shown significant clinical activity as singleagents. Trials are ongoing to incorporate these new agents into thevarious stages of treatment and to combine them with other effectivetreatment modalities, including ASCT.

Recent advances in treatment modalities for breast and prostate cancerhave resulted in an increasing number of patients that are cured orthat, despite residual disease, live long enough to start experiencingcomplications from cancer treatment. Osteoporosis is one such problemthat has been increasingly identified in cancer patients. Hypogonadismand glucocorticoid use are the two major causes of bone loss inthese patients. Osteoporosis is characterized by low bone mass and abnormalbone microarchitecture, which results in an increased risk offractures. Vertebral body and hip fractures commonly result in a drasticchange of quality of life as they can result in disabling chronic pain,loss of mobility, and loss of independence in performing routine dailyactivities, as well as in increased mortality. In patients with prostatecarcinoma, androgen-deprivation therapy by either treatment with agonadotropin-releasing hormone (GnRH) or bilateral orchiectomy resultsin increased bone turnover, significant bone loss, and increasedrisk of fractures. Patients with breast cancer are at increased risk forestrogen deficiency due to age-related menopause, ovarian failure fromsystemic chemotherapy, or from the use of drugs such as aromataseinhibitors and GnRH analogs. Several studies have indicated that theprevalence of fractures is higher in breast and prostate cancer patientscompared to the general population. Therefore, patients at risk for boneloss should have an assessment of their bone mineral density so thatprevention or therapeutic interventions are instituted at an early enoughstage to prevent fractures. This article will address the characteristicsof bone loss observed in breast and prostate cancer patients and potentialtreatments.

Approximately 70% to 80% of all patients who receive chemotherapyexperience nausea and vomiting, which can disrupt their lives in numerousways. Chemotherapy-induced nausea and vomiting (CINV) hastraditionally been classified according to three patterns: acute, delayed,and anticipatory. Additional classifications include refractory and breakthroughnausea and vomiting. The mechanisms by which chemotherapycauses nausea and vomiting are complex, but the most common isthought to be activation of the chemoreceptor trigger zone. An appreciationof the risk factors for developing CINV is important when matchingantiemetic treatment to risk. The emetogenicity of the chemotherapyregimen-generally categorized as high, moderate, low, or minimal-greatly affects a patient’s risk for developing CINV. In addition to establishedand emerging pharmacologic approaches to managing CINV,many complementary and integrated modalities may be options.Progress in CINV management must include a better understanding ofits etiology and a focus on prevention. This review will consider theetiology, assessment, and treatment of patients with CINV.