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Targeted agents differ from cytotoxic chemotherapy in their mechanism of action and clinical outcomes. Similarly, drug development for targeted agents may also differ. Targeted agents are generally better tolerated than chemotherapeutic agents and may have activity at doses lower than maximum tolerated dose (MTD). Optimum drug dosing needs to be based not only on toxicities but also on pharmacokinetic and pharmacodynamic parameters. As cytostatic-targeted agents may induce disease stabilization, time to progression and survival may be a more appropriate outcome of interest than disease regression. Translational research becomes an indispensable part of trials with targeted agents to identify optimum dosing and to identify predictive biomarkers. This includes advances in technology, better understanding of tumor biology, and validation of research techniques. Clinical trials with novel randomization designs have been developed in recent years to optimize identification of drug activity in a targeted population. [ABSTRACT FROM AUTHOR]

Colon and rectal cancers (CRC) are among the most common adult malignancies worldwide, and for a variety of reasons, the numbers of survivors of colorectal cancer are likely to increase in coming years. The incidence of these cancers doubles with each successive decade of life beyond 50 years, and with the expansion of the older population in the coming years, the absolute numbers of CRC patients in the United States will grow substantially.1 It is estimated that by the year 2030 the number of persons over the age of 65 years will have doubled and the number of persons over the age of 85 years will have quadrupled.2 Given this expanding and aging population, projections suggest that the numbers of CRC patients may increase by as much as 30%.3 Thus, with these profound demographic changes, it will be imperative to have a better understanding of the late effects and health care needs of longterm CRC survivors. [ABSTRACT FROM AUTHOR]

Lung cancer emerged during the 20th century as an epidemic of enormous proportions.1 A rare disease at the beginning of the past century, lung cancer continues to be one of the most common cancers in the world, affecting 173,700 Americans (93,110 men and 80,660 women) in 2004.2 Mirroring changes in smoking patterns, the incidence of lung cancer among men continues to decline. Large-scale smoking among women occurred almost 20 years after men in the United States, with a subsequent delay in increased cases, peaking in the 1990s. Encouragingly, the most recent evidence demonstrates that lung cancer incidence among women is declining, as are death rates.3 In 2000, approximately 13% of men and 17% of women (age-adjusted, 15% overall) diagnosed with lung cancer were expected to survive at least 5 years (an estimated 26,065 Americans each year). [ABSTRACT FROM AUTHOR]

Cancer survivors have been shown to have an increased risk for second malignant neoplasms (SMN). These increased risks result from genetic predisposition, harmful environmental exposures, or cancer treatment therapies. Regardless of their cause, SMNs now comprise the sixth most common group of malignancies after skin, prostate, breast, lung, and colorectal cancers.1 It is important to emphasize that the fear of SMN related to the treatment of the first cancer diagnosis should not outweigh the positive effects of curative therapy for the first cancer. Both physicians and patients should, however, be aware of the consequences of the cancer treatment regimens, specifically radiation therapy (RT) and chemotherapy, and consider them while devising follow-up plans. [ABSTRACT FROM AUTHOR]

Malignancies most often produce symptoms by local tumor growth and invasion, or by metastatic spread. However, there are remote effects of the primary cancer termed paraneoplastic that can result in significant symptomatology and organ dysfunction.1 It is postulated that these syndromes result from the production of substances, such as hormones or their precursors, steroid metabolites, enzymes, and various cytokines.2 Neurologic syndromes associated with neoplasms may be the result of antibody production related to immunoaccessible antigens produced by the neoplasm. [ABSTRACT FROM AUTHOR]

Cancer cachexia is a complex syndrome clinically manifest by progressive involuntary weight loss and diminished food intake and characterized by a variety of biochemical alterations. Importantly, cancer cachexia has been associated with increased morbidity and mortality and decreased response to therapy. The impact of cancer cachexia on patient outcome and healthcare resources continues to be significant. It is therefore important to identify those cancer patients who are malnourished in an attempt to reverse or at least abate the progression of malnutrition. The goal of nutritional supplementation is to translate repletion into clinical benefit, thereby decreasing morbidity or mortality and increasing the response rate to treatment. The focus of this chapter is to review the etiology of cancer cachexia, summarize the biologic and clinical effects of nutrition, define specific indications for nutrition in the cancer patient population, and explore new therapies available to reverse cancer cachexia. [ABSTRACT FROM AUTHOR]

Thousands of individual citations using the expression cancer advocacy can be found in contemporary medical and scientific literature as well as in the popular press and on Internet websites. For purposes of this chapter, the term cancer advocacy is used to describe a skill set that has been documented in previously published work by Clark and Stovall. This chapter also includes specific examples of how self-described advocacy organizations are involved with research organizations and how they influence cancer research and related health policy. [ABSTRACT FROM AUTHOR]

Prevalence data on psychosocial morbidity indicate that from 30% to 50% of cancer patients may experience distress significant enough to warrant professional intervention at some time during survivorship. These patients may require professional attention to manage the debilitating effects of diagnosis, treatment, and morbidity that can wax and wane over time depending upon a host of other variables. It is in this group that some form of psychosocial rehabilitation may be useful. [ABSTRACT FROM AUTHOR]

Survival rates for hematopoietic cell transplantation (HCT) have improved with advances in supportive care that have reduced acute, transplant-related mortality. More than 40,000 transplants were performed worldwide in 2002, mostly for the treatment of leukemia, lymphoma, or multiple myeloma1 (see Chapters 63 through 69 for discussions of specific diseases). The probability of successful transplantation is generally greater for patients transplanted early in their disease course, for younger patients, and for patients who receive stem cells from donors whose human leukocyte antigens (HLA) match the patient's. For survivors who receive HCT for acute leukemia or chronic myeloid leukemia and who remain free of disease after 2 years, the probability of living 5 or more years is 89%. [ABSTRACT FROM AUTHOR]

Anxiety and depression can be viewed as part of a broader construct of psychologic distress. We chose to focus on anxiety and depression rather than on psychologic distress for several reasons. First, the literature on anxiety and depression can be more readily identified than the literature on the broader and less well defined construct of psychologic distress. Second, as described in the following, criteria have been established for the diagnosis of clinical syndromes of anxiety and depression; no similar criteria exist for the diagnosis of clinical syndromes of psychologic distress. Third, as described here, this approach allows us to build upon the findings of several previous systematic reviews and meta-analyses that also have focused on psychosocial and pharmacologic approaches to the management of anxiety and depression in adult cancer patients. [ABSTRACT FROM AUTHOR]

Of the more than 200,000 men diagnosed each year with prostate cancer in the United States,1 most live with their disease or the effects of treatment for many years.2 Although many men remain asymptomatic throughout their lives, others face a multitude of physical and psychosocial challenges. Because the duration of survival is typically long, patients and their families are particularly interested in optimizing their quality of life. At the generic level, health-related quality of life (HRQOL) encompasses an individual's perceptions of his or her own health and ability to function in the physical, emotional, and social domains.3,4 In prostate cancer survivors, the medical outcomes of urinary, bowel, and sexual impairments that result from treatment will influence the rest of the patient's life. The psychosocial aspects of HRQOL are impacted by the intimate nature of these medical side effects. Urinary leakage and erectile dysfunction may cause both private and public social embarrassment. In addition, such treatment-related complications may be compounded by the additional stressors associated with aging, such as retirement or death of peers.5 Nearly onethird of men diagnosed with prostate cancer in a genitourinary clinic had levels of psychologic distress that met criteria for anxiety disorder. [ABSTRACT FROM AUTHOR]

Testicular cancer (TC) is the most frequent malignancy in men between 20 and 40 years of age, and the annual incidence rates are continuously increasing in the Western world.1 Since the introduction of cisplatin-based chemotherapy, at least 90% of the patients are cured,2 and testicular cancer survivors (TCSs) currently have a life expectancy similar to that of age-matched normal men, with posttreatment life spans of 30 to 50 years. Thus, an increasing number of TCSs experience survivorship problems related to the malignancy, its treatment, or both. [ABSTRACT FROM AUTHOR]

Women with breast cancer account for the largest group of female cancer survivors. It is estimated that there are currently 8.9 million cancer survivors in the United States; 41% of the female subjects are breast cancer survivors.1 The growing number of breast cancer survivors reflects increasing incidence of the disease, diagnosis at earlier stages when outcome is better, and widespread adoption of effective adjuvant treatment (see Chapter 28 and Chapter 54). [ABSTRACT FROM AUTHOR]

An emerging body of research has documented the quality of life of women with gynecologic cancer around the time of diagnosis and during treatment. However, we know much less about the quality of life and psychosocial and medical needs of gynecologic cancer survivors after treatment.1,2 In particular, there are very few studies documenting the risk of possible late medical effects of gynecologic cancer treatment such as osteoporosis and second primary cancers. More is known about self-reported symptoms and psychosocial sequelae, such as sexual functioning and psychologic distress, but even these studies rarely focus on survivors more than 5 years after diagnosis. Additionally, much of the extant research has limitations such as small sample sizes, nonstandardized measures, and crosssectional designs, often without appropriate comparison groups. Finally, there is a dearth of research testing interventions to ameliorate problems experienced by gynecologic cancer survivors. While in some areas additional research is needed to better describe the sequelae and determine who is at risk for adverse late effects, in others areas (e.g., sexual functioning), adequate data describing the problem are available, and a stronger focus on treatment interventions is needed. (See also Chapter 90, Reproductive Complications and Sexual Dysfunction in the Cancer Patient.) [ABSTRACT FROM AUTHOR]

The first attempts to treat Hodgkin's disease by radiotherapy were conducted at the beginning of the last century. The prognosis for survival was poor but slowly improved by the use of radiotherapy and some chemotherapy until 1960. For example, in 1939 a 20-year survival rate of 17% was reported. [ABSTRACT FROM AUTHOR]

More than 12,000 children and adolescents younger than 20 years are diagnosed with cancer each year in the United States.1 With the use of risk-based therapies, the overall 5-year survival rate is approaching 80%, resulting in a growing population of childhood cancer survivors. In 1997, there were an estimated 270,000 survivors of childhood cancer; over two-thirds of these were older than 20 years of age.2 This figure translates into 1 in 810 individuals under the age of 20 and 1 in 640 individuals between the ages of 20 and 39 years having successfully survived childhood cancer (see Chapter 62). [ABSTRACT FROM AUTHOR]

With continued advances in strategies to detect cancer early and treat it effectively, along with the aging of the population, the number of individuals living years beyond a cancer diagnosis can be expected to continue to increase. Statistical trends show that, in the absence of other competing causes of death, 64% of adults diagnosed with cancer today can expect to be alive in 5 years. Relative 5-year survival rates for those diagnosed as children (age less than 19 years) are even higher, with almost 79% of childhood cancer survivors estimated to be alive at 5 years and 75% at 10 years. [ABSTRACT FROM AUTHOR]

In 1884, an official ceremony was held and the cornerstone laid for an ornate and turreted building in New York City that would for many years house the first cancer treatment center in the country. The site, located on the upper west side of Central Park, then a virtual wilderness area on the larger island of Manhattan, was selected because the belief at the time was that cancer was contagious. The rounded design of the towers, where patient beds were to be located, was intended to discourage the risk of germs, which were thought to lurk in corners. Named The New York Cancer Hospital, this institution would later be moved in 1948 to its current east side location where it was, until 1960, called the Memorial Hospital for Cancer and Allied Diseases. The history of this leading center for cancer care and research, known today as the Memorial Sloan-Kettering Cancer Center, a sprawling multisite enterprise, is illustrative of where we have come in viewing cancer. [ABSTRACT FROM AUTHOR]

One in every 1,000 pregnant women will be diagnosed with cancer.1 Despite this fact, the level of evidencebased medicine available in the field of cancer during pregnancy is low. Randomized controlled trials in this area do not exist. Instead, retrospective collections of patients treated with varying treatment regimens and strategies, collected case reports, studies based on events, such as the Japanese atomic bomb experience, and, for rare malignancies, isolated case reports generally constitute the medical literature on pregnancy and cancer. Nonetheless, this chapter may guide oncologists facing patients in this relatively uncommon, but serious position. We discuss the use of the major diagnostic and treatment modalities in oncology during pregnancy: surgery, diagnostic imaging and therapeutic radiation, and antineoplastic agents. Therapeutic strategies for malignancies seen most frequently during pregnancy are addressed: these include breast cancer, cancer of the uterine cervix, Hodgkin's disease, and non-Hodgkin's lymphoma. Medical management of symptoms of malignancy and its treatment that are unique to the pregnant patient are discussed. [ABSTRACT FROM AUTHOR]

Clinical studies of chemotherapy, or other antineoplastic therapies, are usually conducted in physiologically otherwise normal patients with cancer. As a result, limited information is typically available about the optimal dosage and schedule of chemotherapy for patients with organ dysfunction and the impact of chemotherapy in such patients. This is a potentially important problem, because most chemotherapies, as with other pharmacologic agents, are metabolized by the liver or kidney. Over the past decade, a concerted effort has been made to focus on chemotherapy in this patient population. The new generation of biologic therapies may not possess this difficulty, as the monoclonal antibodies that, to date, comprise the most successful of these agents are metabolized by the reticuloendothelial system and may not require these modifications. However, these concerns regarding the appropriate administration of antineoplastic agents will persist with the new small molecule inhibitors, including tyrosine kinase inhibitors, which also may require individual evaluation in patients with organ dysfunction. [ABSTRACT FROM AUTHOR]

Advancing age comes bundled with increased cancer incidence and mortality. Indeed, the median age at diagnosis of all cancers combined is 69 years for men and 67 for women.3 Age-adjusted cancer incidence is 10 times higher in the 65+ population compared to their younger counterparts (2,151.2 versus 208.8/100,000 persons).2 Similarly, age-adjusted cancer mortality is 15-fold higher in the 65+ population (1,068.2 versus 67.3/100,000 persons). Figure 97.1 illustrates the proportions of the commonest cancers incidence and mortality in the 65+ population. As a result, although the total U.S. population is expected to grow by 9% between 1990 and 2010, the incidence of cancer is expected to increase by a disproportionate 32% in the same time frame. These trends are mirrored in countries across the globe. [ABSTRACT FROM AUTHOR]

During the 1960s, as oncology research was rapidly expanding, MacFarlane Burnett's idea that cancer resulted from a failure of tumor surveillance by the aging immune system was broadly acknowledged. The development of cancer genetics focused the field on mutational causes of tumorigenesis. However, a new appreciation for the role that a well-functioning immune system plays in protecting against virally induced tumors was brought to light in the 1980s with the acquired immunodeficiency syndrome (AIDS) epidemic. The phenomenon of the human immunodeficiency virus (HIV)-associated cancer epidemic within defined populations, particularly due to the recent dramatic responses to treatment of the underlying immunodeficiency, has given insight into other etiologic factors for a variety of tumors. [ABSTRACT FROM AUTHOR]

Metastatic disease to bone is the most common malignancy of bone. The American Cancer Society estimated that in 2004 there will have been 1,368,030 new cases of cancer in the United States.1 Of these, they estimated that approximately 2,400 will be new cases of primary bone malignancy; that is, compared with over 230,000 new cases of prostate carcinoma, 217,000 cases of breast carcinoma, and 173,000 cases of lung carcinoma. Those three diagnoses, along with kidney cancer and thyroid carcinoma, represent 80% of metastases to the skeleton.2 Autopsy studies have shown that 50% to 70% of patients with prostate cancer develop metastases and 85% of patients with breast cancer develop skeletal metastases. The skeleton is surpassed only by the lungs and liver for incidence of metastatic disease. Any bone of the skeleton can be involved; however, the axial skeleton is most commonly involved. Involvement of the appendicular skeleton most commonly involves the proximal portion of the lower extremities. Within the spine, it is primarily the anterior and middle columns that are involved. [ABSTRACT FROM AUTHOR]

The liver is a frequent site of metastases from solid tumors and the most common site of distant metastases from colon and rectal cancer. Death from colon and rectal cancer is usually a result of metastatic disease. In one study, more than one-half of patients who died of colon and rectal cancer had liver metastases at autopsy, and the majority of these patients died as a result of their metastatic liver disease.1 Unlike many types of cancer, however, the presence of distant metastases from colon and rectal cancer does not necessarily preclude curative treatment. Nearly 40% of patients with colon and rectal cancer and hematogenous metastases have disease that is predominantly in the liver. Moreover, in a subpopulation of patients, the number of lesions is limited. Accordingly, there exists a strong rationale for regional therapies directed specifically against colon and rectal cancer liver metastases. This pattern of metastases is rarely observed in other cancers. [ABSTRACT FROM AUTHOR]