Population pharmacokinetic analysis of the major metabolites of capecitabine.

Capecitabine has been developed as an orally administered tumor selective fluoropyrimidine for use in the treatment of breast and colorectal cancer. The metabolic pathway for capecitabine includes 5'-deoxy-5-fluorocytidine (5'-DFCR) and 5'-deoxy-5-fluorouridine (5'-DFUR), which is then converted to the pharmacologically active agent 5-fluorouracil (5-FU). A previous analysis showed that systemic exposure to 5'-DFUR and alpha-fluoro-beta-alanine (FBAL), a catabolite of 5-FU, was predictive of dose limiting toxicities. Therefore, a multi-response population pharmacokinetic (PK) model for the description of plasma concentrations of 5'-DFUR, 5-FU and FBAL following oral administration of capecitabine was developed using NONMEM. PK data from a bioequivalence study in 24 patients with various solid tumors were used to develop the PK structural part of the population PK model. The 5'-DFUR, 5-FU and FBAL plasma concentrations were described by a linear disposition PK model with first order absorption and lag time. Sparse plasma concentration data from 54 phase II breast cancer patients were added to the bioequivalence data and the influence of covariates on the apparent oral clearances of 5'-DFUR, 5-FU and FBAL and on the apparent volume of distribution of FBAL was investigated. This was conducted by including all significant (p < 0.05) single covariate-PK parameter pairs in the full PK model, followed by one by one deletion (p < 0.001) from the population model. Statistically significant effects were found for the influence of gender, body surface area and total bilirubin on 5'-DFUR clearance and the influence of creatinine clearance on FBAL clearance. However, none of these effects were considered to have clinical relevance.

Rehabilitation of the cancer patient at home.

OBJECTIVES: To provide a framework for considering home nursing care of the cancer patient within the context of cancer rehabilitation and to briefly review various aspects of cancer rehabilitation. DATA SOURCES: Review articles and reference books of current and classic works that discuss cancer rehabilitation. CONCLUSIONS: Rehabilitation is an important concept that should transcend cancer care in all settings, and one that naturally fits with home care. The effects of cancer and cancer treatment on the individual's quality of life, eg, psychological and social factors, sexual functioning, nutrition, fitness and exercise, symptom management, and physical disabilities are important considerations in the rehabilitation needs of persons with cancer. IMPLICATIONS FOR NURSING PRACTICE: It is the challenge of the home health nurse to promote optimal functioning of cancer patients in their home environment. Assessment of the cancer patient's rehabilitation needs, skilled interventions, establishment of realistic goals, and coordinating care between members of the rehabilitation team are major responsibilities.

Applying the realized probability of dying to cancer survival.

Age comparisons of survival in cancer cohorts generally utilize relative survival rates, which are based on indicators of the probability of survival for a given number of years after diagnosis. Cancer relative survival rates for the same number of years tend to decline as age at diagnosis increases. However, the same number of years of survival reflects higher relative longevity at older ages than at younger ages. The realized probability of dying (RPD) is a survival measure that expresses individual survival time after diagnosis relative to the survival distribution of an age-, race-, and sex-specific reference population, in effect weighing individual survival time more heavily as age at diagnosis increases. The purpose of this study was to apply the RPD as a survival measure in cancer epidemiology. Two cohorts of cancer patients, white males with prostate cancer and white females with breast cancer, aged 55 years and over at diagnosis, were followed for 15 years. Although older subjects survived less time after diagnosis than younger subjects, they achieved more favorable RPD values. We present survival analysis methods for analyzing the RPD in this population, an approach not previously used with this measure. The implications for use of the RPD in cancer epidemiology are discussed.

Life cycle issues affecting cancer rehabilitation.

Developmental stage of the person with cancer has a profound effect on the rehabilitation plan. Although the issues faced by the very young and the elderly are quite different, the struggle to maintain optimal function is universal. As we continue to see improved survival rates and cures, the need for comprehensive rehabilitative care for all persons experiencing cancer becomes a challenge. Our success in meeting this challenge will be realized in measurable outcomes that will direct future rehabilitative care.

Biology of cancer and aging.

The greatest risk factor for cancer is aging. Human cancer incidence increases exponentially with advancing age. Cancer growth rate and potential for metastatic spread may be influenced by age-specific change in host response. Because cancer and aging are, thus, inextricably linked, the American Cancer Society should encourage submission of research proposals that address the mechanisms of aging and how aging alters cancer development.

Cervical cancer screening in older women. Issues and interventions.

Although some controversy exists, the Papanicolaou (Pap) smear for cervical cancer screening is widely accepted as an effective mechanism for cancer control. An issue of interest to clinicians and behavioral scientists is the underrepresentation of elderly women in populations screened. It is important for nurses to understand the issues, and hypothesized reasons behind this phenomenon, in order to develop interventions to counteract it. The authors examine this problem from a number of behavioral and clinical perspectives and discuss nursing interventions to improve cervical cancer screening in older women.

Correlates of fatigue in people with breast or lung cancer.

Fatigue is regarded as a universal and unavoidable side effect of cancer therapy, yet its epidemiology and prevalence in populations of people with cancer have not been well-documented. Using the conceptual framework of Piper, et al., this study examined and described the perception and manifestations of fatigue and its physiological, biochemical, and behavioral correlates. A convenience sample (N = 77) of people with lung (n = 33) or breast cancer (n = 44) completed several instruments: a brief questionnaire, the Rhoten Fatigue Scale, a visual analogue scale (VAS), the Rhoten Fatigue Checklist, and the shortened version of the Profile of Mood States (POMS). Data on other factors thought to influence fatigue were collected via medical record audit. Seventy-five of 76 people (99%) completing the VAS experienced some level of fatigue. Significant correlates of fatigue included level of pain and POMS scores. Preliminary findings suggest that fatigue is a common problem with a complex etiology and that nurses must consider potential contributing factors when assessing fatigue and its impact on the individual.

Collaborative research under the unification model.

The research role of the clinical nurse specialist is often the most difficult to implement. At the masters level, efforts are generally directed at utilization and evaluation of research more than design and implementation. Collaboration between several investigators, however, is an efficient and effective method of pooling the resources of a variety of researchers, allowing the actualization of all aspects of the research process. A collaborative effort to look at the clinical problem of fatigue was undertaken by a group of masters-prepared oncology nurses. Strategies for effective collaboration are outlined. Issues related to gaining group commitment and to delineating roles at the onset, voluntary participation, and timely communication are discussed. A realistic timetable and regular informal meetings helped to sustain the momentum of the study. All members were able to contribute a part of the completed project and to experience the professional and personal satisfaction of "owning" a research project from start to finish.

Timely detection of colorectal cancer in the elderly. Implications of the aging process.

Increased age is a risk factor for colorectal cancer; however, there is a lack of literature that focuses on the early detection of colorectal cancer in the elderly. The nursing process provides the conceptual basis for this article, which discusses normal bowel function, aging changes in the bowel, and colorectal cancer. A nursing care plan for alterations in bowel elimination/constipation is presented as a model.