Has demand for clinical trial participants outpaced supply?
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Breast Neoplasms↗
Biomedical subjects
Stuart M Lichtman
Publications and source records attributed to Stuart M Lichtman.
International Society of Geriatric Oncology (SIOG) recommendations for the adjustment of dosing in elderly cancer patients with renal insufficiency.
A SIOG taskforce was formed to discuss best clinical practice for elderly cancer patients with renal insufficiency. This manuscript outlines recommended dosing adjustments for cancer drugs in this population according to renal function. Dosing adjustments have been made for drugs in current use which have recommendations in renal insufficiency and the elderly, focusing on drugs which are renally eliminated or are known to be nephrotoxic. Recommendations are based on pharmacokinetic and/or pharmacodynamic data where available. The taskforce recommend that before initiating therapy, some form of geriatric assessment should be conducted that includes evaluation of comorbidities and polypharmacy, hydration status and renal function (using available formulae). Within each drug class, it is sensible to use agents which are less likely to be influenced by renal clearance. Pharmacokinetic and pharmacodynamic data of anticancer agents in the elderly are needed in order to maximise efficacy whilst avoiding unacceptable toxicity.
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Prospective evaluation of the relationship of patient age and paclitaxel clinical pharmacology: Cancer and Leukemia Group B (CALGB 9762).
PURPOSE: To prospectively evaluate the pharmacokinetics and toxicity profile of paclitaxel in relation to patient age in adults > or = 55 years old. PATIENTS AND METHODS: Paclitaxel was administered at 175 mg/m2 for 3 hours to 153 patients, 46 of whom were > or = 75 years of age. Pharmacokinetic and toxicity assessments were performed. Data were analyzed by cohort (cohort 1, age 55 to 64 years; cohort 2, age 65 to 74 years; cohort 3, age > or = 75 years). RESULTS: Paclitaxel concentration versus time (AUC) and total-body clearance (CL(tb)) data were available for 122 patients (cohort 1, 46 patients; cohort 2, 44 patients; cohort 3, 32 patients). Mean paclitaxel AUC increased across cohorts (P = .01). Mean (SE) AUCs were 22.4 (2.5) micromol/L x hour, 26.2 (2.8) micromol/L x hour, and 31.7 (5.6) micromol/L x hour for cohorts 1, 2, and 3, respectively. There was a corresponding significant (P = .007) age-related decrease in mean (SE) paclitaxel CL(tb) (cohort 1, 11.0 [0.7] L/h/m2; cohort 2, 9.3 [0.6] L/h/m2; cohort 3, 8.2 [0.6] L/h/m2). Patients in cohort 3 experienced significantly lower absolute neutrophil count nadirs than did younger groups (P = .02). There was also a significant increase in percentage of patients with > or = grade 3 neutropenia across age cohorts (cohort 1, 22%; cohort 2, 35%; cohort 3, 49%; P = .006). However, the increased exposure of patients to paclitaxel and increased neutropenia were not reflected in adverse clinical sequelae such as hospitalization for toxicity (P = .82), receiving intravenous antibiotics (P = .21), or experiencing a temperature more than 38 degrees C (P = .45). CONCLUSION: Although paclitaxel CL(tb) decreases with increasing patient age, there is great interpatient variability. Cooperative group studies to evaluate the effect of aging on pharmacokinetics are feasible.
Age Factors↗
Therapy insight: Therapeutic challenges in the treatment of elderly cancer patients.
People over the age of 65 years constitute the fastest-growing segment of the US population. Within the next 30 years, this group will comprise over 20% of the total population. Importantly, 50% of all cancers and 70% of cancer mortality occur in this age group. Choosing the correct chemotherapy regimen and dose for the older patient can be extremely difficult because of physiological changes that occur with aging, as well as other comorbidities associated with this age group. Treatment decisions need to be based on a patient's individual performance, functional status and life expectancy. Although there are no accepted algorithms to guide management decisions in elderly cancer patients, data are becoming available that will help guide the use of chemotherapy in the older patient population.
Age Factors↗
Management of colorectal cancer in older patients.
An increasing body of evidence suggests that geriatric patients can benefit from and tolerate standard chemotherapy similarly to younger patients in the settings of both early- and advanced-stage colorectal cancer. Assessment of this unique population requires more comprehensive evaluation in addition to routine history, physical examination, and laboratory tests. Specific considerations of their physiologic functional changes will help physicians better manage these patients. Ongoing studies are now designed to better understand the decisionmaking process, safety profile, and efficacy of various treatment regimens in geriatric patients.
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Unusual uterine recurrence of primary central nervous system lymphoma.
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Adult↗
Treatment of elderly cancer patients with chemotherapy.
Persons over the age of 65 are the fastest growing segment of the United States population. In the next 30 years, they will comprise over 20 percent of the population. Fifty percent of all cancers occur in this age group and, therefore, there will be an expected rise in the total cancer burden. Data is becoming available that will better guide the use of chemotherapy in the older patient population. Information regarding age-related physiologic changes are presented with their relationship to pharmacology, functional status, and hematopoiesis. Treatments are reviewed in regard to the adjuvant treatment of breast and colon cancer as well as primary therapy of aggressive non-Hodgkin's lymphoma. The treatment of more advanced breast, ovary and non-small cell lung cancer also are discussed.
Aged↗
Clinical pharmacology issues relevant to the dosing and toxicity of chemotherapy drugs in the elderly.
Persons over the age of 65 years are the fastest growing segment of the U.S. population. In the next 30 years, they will comprise more than 20% of the population. Fifty percent of all cancers occur in this age group, and therefore, there is an expected rise in the total cancer burden. Data are becoming available that will better guide the use of chemotherapy in the older patient population. In this paper, information regarding age-related physiologic changes and their relationship to pharmacology, functional status, and hematopoiesis is presented. The adjuvant treatment of breast and colon cancer, as well as the primary therapy of aggressive non-Hodgkin lymphoma is reviewed. The treatment of more advanced breast, ovarian, and non-small cell lung cancer is also discussed.
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Management of advanced colorectal cancer in older patients.
Many elderly individuals have substantial life expectancy, even in the setting of significant illness. There is evidence to indicate that elderly individuals derive as much survival benefit as younger patients from standard chemotherapy approaches in advanced colorectal cancer. Effective treatments should not be withheld from older patients on the basis of age alone. Treatment decisions should be based on functional status, presence of comorbidities, and consideration of drug-specific toxicities that can be exacerbated in older individuals due to decreased functional reserve. Infusional and weekly fluorouracil (5-FU) regimens are better tolerated than bolus and monthly regimens. Oral capecitabine (Xeloda) reduces the frequency of a number of toxicities compared with bolus 5-FU, including stomatitis, a particularly debilitating toxicity in many elderly patients. The effectiveness and tolerability of oxaliplatin and irinotecan (Camptosar) appear to be similar in older and younger patients. Older patients can also receive bevacizumab (Avastin), although caution is warranted in those with cardiovascular disease. Overall survival in metastatic colorectal cancer improves with the availability of multiple effective chemotherapeutic agents. The full range of effective therapies in advanced colorectal cancer should be extended to elderly patients.
Age Factors↗
Prospective evaluation of body surface area as a determinant of paclitaxel pharmacokinetics and pharmacodynamics in women with solid tumors: Cancer and Leukemia Group B Study 9763.
PURPOSE: To study a fixed dose (360 mg) of paclitaxel given i.v. over 3 hours to female patients, and to evaluate prospectively the relationships between the following: body surface area and toxicity; body surface area and pharmacokinetics; and pharmacokinetics and toxicity. EXPERIMENTAL DESIGN: The eligibility criteria included the following: female sex; solid tumors; no more than one prior chemotherapy regimen; no prior paclitaxel; performance status of 0 to 2; and normal organ function. Paclitaxel plasma concentrations were quantified by high-performance liquid chromatography. The area under the curve, total body clearance, and hours above 0.05 micromol/L (T > 0.05) were calculated. RESULTS: Thirty-two patients were enrolled, and 29 patients received the correct dose and regimen. For statistical analyses, 26 patients had complete follow-up blood counts, 23 patients had complete data to correlate blood counts and area under the curve, and 25 patients had data to correlate blood counts and T > 0.05. The main toxicity was neutropenia of grade 3 and 4 severity in 21% and 25% of patients, respectively, in cycle 1. The worst grade of any toxicity, nadir WBC and absolute neutrophil count, and survival fractions were assessed; no significant relationship was found between body surface area and any measure of toxicity. Body surface area correlated inversely with area under the curve (r = -0.67; P < 0.001) and correlated with total body clearance (r = 0.69; P < 0.001), but body surface area did not correlate with T > 0.05. Neither area under the curve nor total body clearance were correlated with nadir absolute neutrophil count or survival fractions, but a significant correlation was found between T > 0.05 and log(nadir absolute neutrophil count; r = -0.41; P = 0.04). CONCLUSIONS: These results suggest that fixed dosing of paclitaxel is feasible in women, which would simplify the administration of this drug.
Adult↗
Unusual abdominal tumors, case 1. Pseudomyxoma peritonei: response to capecitabine.
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Abdominal Neoplasms↗
Chemotherapy in the elderly.
Persons over the age of 65 years are the fastest growing segment of the US population. In the next 30 years it will comprise over 20% of the population. More than 50% of all cancers occur in this age group and therefore, the total cancer burden is expected to rise. Data are becoming available that will better guide the use of chemotherapy in the older patient population. Understanding the physiologic and functional changes that occur with aging will assist in developing useful strategies in the elderly. Pharmacokinetic data on a broad spectrum of chemotherapeutic agents will be presented. Many of these agents seem to have a beneficial therapeutic index, particularly in older patients. There has also been an increasing trend toward the use of oral chemotherapy. Factors that must be considered in choosing chemotherapy include limitations of saturability of absorption, patient compliance, and the pharmacokinetic and pharmacodynamic changes that occur in older patients. Interpatient variability and age-related changes in drug metabolism are discussed. Careful attention to the physiologic changes with age and dose adjustments necessary for end organ dysfunction (renal, hepatic) are needed to ensure the safe administration of chemotherapy to older patients.
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Pharmacology of antineoplastic agents in older cancer patients.
Persons over the age of 65 years are the fastest growing segment of the United States population. In the next 30 years it will comprise over 20% of the population. Fifty percent of all cancers occur in this age group and therefore there will be an expected rise in the total cancer burden. Data is becoming available which will better guide the use of chemotherapy in the older patient population. Studies will be presented discussing pharmacokinetic data on a number of chemotherapeutic agents with an emphasis on those which have entered practice over the past few years. Many of these agents seem to have a beneficial therapeutic index, particularly in regard to older patients. There has also been an increasing trend toward the use of oral chemotherapy. Factors that must be considered in choosing chemotherapy include limitations of saturability of absorption, patient compliance and the pharmacokinetic and pharmacodynamic changes which occur in older patients. Interpatient variability and age related changes in drug metabolism are discussed. Careful attention to the physiologic changes with age, and dose adjustments necessary for end organ dysfunction (renal, hepatic) are needed to ensure the safe administration of chemotherapy.
Administration, Oral↗
The pharmacokinetics and pharmacodynamics of fludarabine phosphate in patients with renal impairment: a prospective dose adjustment study.
UNLABELLED: A significant number of chronic lymphocytic leukemia, follicular non-Hodgkin's lymphoma and Waldenström's macroglobulinemia patients, treated with fludarabine phosphate (fludarabine), are elderly with diminished renal function. Since the kidney eliminates approximately 60% of fludarabine's primary metabolite (F-ara-A), dose modification is necessary for all patients with impaired renal function including elderly patients. In this study, 22 patients with varying levels of renal function received a single intravenous dose of fludarabine (25 mg/m3), followed one week later by five (one per day) doses that were adjusted according to three predefined creatinine clearance (CLcr) levels. Relationships between renal function and F-ara-A clearance, F-ara-A exposure and F-ara-A--related toxicities were examined. The results demonstrate that total F-ara-A clearance correlated with CLcr and that F-ara-A exposure levels and patient toxicity profiles were similar across treatment groups. IN CONCLUSION: The CLcr-based fludarabine dose adjustments used in this study provided reasonably equivalent F-ara-A exposure with acceptable safety in patients with varying degrees of renal function.
Adult↗
Pharmacokinetic considerations of oral chemotherapy in elderly patients with cancer.
Persons over the age of 65 years are the fastest growing segment of the US population. In the next 30 years they will comprise over 20% of the population. Fifty per cent of all cancers occur in this age group and therefore there will be an expected rise in the total cancer burden. There has been an increasing trend over the past 20 years toward the use of oral chemotherapy. This change has been encouraged by the need to decrease the costs of chemotherapy administration, patient preferences and quality of life issues. Factors that must be considered with oral chemotherapy administration include limitations of saturability of absorption, patient compliance and pharmacokinetic/pharmacodynamic changes which occur in elderly patients. Interpatient variability and drug metabolism, particularly age-related changes in drug metabolism are being studied. The cytochrome P450 system has been intensively studied because of its importance with regard to chemotherapeutic drugs. This article reviews these issues and provides details regarding specific drugs including temozolomide, thalidomide, topotecan, the fluoropyrimidines, etoposide, hydroxycarbamide (hydroxyurea), tamoxifen, and alkylating drugs. Complementary and alternative therapies are also discussed.
Administration, Oral↗
Care of elderly women with ovarian cancer.
The goal of this article is to educate nurses about ovarian cancer in older women, its treatment options, and related nursing interventions. This information will enable readers to identify risk factors for ovarian cancer, standard treatment approaches, nursing interventions, and patient care.
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Guidelines for the treatment of elderly cancer patients.
BACKGROUND: The management of elderly patients with cancer is influenced by several factors that can vary widely among aging individuals. As the proportion of elderly individuals increases, the need for specific care guidelines for this population is critical. The National Comprehensive Cancer Network (NCCN) has developed guidelines to address these factors when formulating optimal treatment regimens for elderly patients and to avoid significant toxicity and maintain their quality of life. METHODS: Factors that influence the appropriate treatment choices for the elderly, such as functional status, comorbidity, polypharmacy, and the presence of anemia, are reviewed, and the guidelines developed by the NCCN for treatment elderly patients are discussed. RESULTS: The guidelines address these factors when defining the goal of therapy and formulating individualized treatment approaches for the elderly to provide optimal care for these patients, avoid significant toxicity, and maintain their quality of life. CONCLUSIONS: The goal of therapy must be clearly defined, whether survival, remission, cure, or palliation of symptoms. Enrollment of elderly cancer patients onto clinical trials is encouraged so the guidelines can be validated.
Aged↗