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      Appropriate Chemotherapy Dosing for Obese Adult Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline

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          Abstract

          Purpose

          To provide recommendations for appropriate cytotoxic chemotherapy dosing for obese adult patients with cancer.

          Methods

          The American Society of Clinical Oncology convened a Panel of experts in medical and gynecologic oncology, clinical pharmacology, pharmacokinetics and pharmacogenetics, and biostatistics and a patient representative. MEDLINE searches identified studies published in English between 1996 and 2010, and a systematic review of the literature was conducted. A majority of studies involved breast, ovarian, colon, and lung cancers. This guideline does not address dosing for novel targeted agents.

          Results

          Practice pattern studies demonstrate that up to 40% of obese patients receive limited chemotherapy doses that are not based on actual body weight. Concerns about toxicity or overdosing in obese patients with cancer, based on the use of actual body weight, are unfounded.

          Recommendations

          The Panel recommends that full weight–based cytotoxic chemotherapy doses be used to treat obese patients with cancer, particularly when the goal of treatment is cure. There is no evidence that short- or long-term toxicity is increased among obese patients receiving full weight–based doses. Most data indicate that myelosuppression is the same or less pronounced among the obese than the non-obese who are administered full weight–based doses. Clinicians should respond to all treatment-related toxicities in obese patients in the same ways they do for non-obese patients. The use of fixed-dose chemotherapy is rarely justified, but the Panel does recommend fixed dosing for a few select agents. The Panel recommends further research into the role of pharmacokinetics and pharmacogenetics to guide appropriate dosing of obese patients with cancer.

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          Most cited references118

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          Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults

          The influence of excess body weight on the risk of death from cancer has not been fully characterized. In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites. Copyright 2003 Massachusetts Medical Society
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            The obesity epidemic in the United States--gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis.

            This review of the obesity epidemic provides a comprehensive description of the current situation, time trends, and disparities across gender, age, socioeconomic status, racial/ethnic groups, and geographic regions in the United States based on national data. The authors searched studies published between 1990 and 2006. Adult overweight and obesity were defined by using body mass index (weight (kg)/height (m)(2)) cutpoints of 25 and 30, respectively; childhood "at risk for overweight" and overweight were defined as the 85th and 95th percentiles of body mass index. Average annual increase in and future projections for prevalence were estimated by using linear regression models. Among adults, obesity prevalence increased from 13% to 32% between the 1960s and 2004. Currently, 66% of adults are overweight or obese; 16% of children and adolescents are overweight and 34% are at risk of overweight. Minority and low-socioeconomic-status groups are disproportionately affected at all ages. Annual increases in prevalence ranged from 0.3 to 0.9 percentage points across groups. By 2015, 75% of adults will be overweight or obese, and 41% will be obese. In conclusion, obesity has increased at an alarming rate in the United States over the past three decades. The associations of obesity with gender, age, ethnicity, and socioeconomic status are complex and dynamic. Related population-based programs and policies are needed.
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              CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma.

              The standard treatment for patients with diffuse large-B-cell lymphoma is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Rituximab, a chimeric monoclonal antibody against the CD20 B-cell antigen, has therapeutic activity in diffuse large-B-cell lymphoma. We conducted a randomized trial to compare CHOP chemotherapy plus rituximab with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. Previously untreated patients with diffuse large-B-cell lymphoma, 60 to 80 years old, were randomly assigned to receive either eight cycles of CHOP every three weeks (197 patients) or eight cycles of CHOP plus rituximab given on day 1 of each cycle (202 patients). The rate of complete response was significantly higher in the group that received CHOP plus rituximab than in the group that received CHOP alone (76 percent vs. 63 percent, P=0.005). With a median follow-up of two years, event-free and overall survival times were significantly higher in the CHOP-plus-rituximab group (P<0.001 and P=0.007, respectively). The addition of rituximab to standard CHOP chemotherapy significantly reduced the risk of treatment failure and death (risk ratios, 0.58 [95 percent confidence interval, 0.44 to 0.77] and 0.64 [0.45 to 0.89], respectively). Clinically relevant toxicity was not significantly greater with CHOP plus rituximab. The addition of rituximab to the CHOP regimen increases the complete-response rate and prolongs event-free and overall survival in elderly patients with diffuse large-B-cell lymphoma, without a clinically significant increase in toxicity.
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                Author and article information

                Journal
                Journal of Clinical Oncology
                JCO
                American Society of Clinical Oncology (ASCO)
                0732-183X
                1527-7755
                May 01 2012
                May 01 2012
                : 30
                : 13
                : 1553-1561
                Affiliations
                [1 ]Jennifer J. Griggs, University of Michigan, Ann Arbor, MI; Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA; Holly Anderson, Breast Cancer Coalition of Rochester; Michelle Shayne, University of Rochester Medical Center, Rochester; Lara E. Sucheston, Roswell Park Cancer Institute, Cancer Prevention and Control, Buffalo, NY; Edward P. Balaban, University of Pittsburgh Cancer Centers Network, Pittsburgh, PA; James J. Dignam, University of Chicago, Chicago, IL; William M. Hryniuk,...
                Article
                10.1200/JCO.2011.39.9436
                22473167
                fbb3aff1-0565-406b-9534-e9e91a6a0b0e
                © 2012
                History

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