Biomedical subjects
G A Curt
Publications and source records attributed to G A Curt.
[Fatigue syndrome caused by malignant tumor. An increasing priority in patient care].
As oncologists have become more effective in alleviating pain, nausea and depression, fatigue has emerged as the most important symptom suffered by cancer patients. Indeed, the current literature suggests that fatigue is currently the most important untreated symptom in cancer medicine. In recent surveys of patients and their caregivers, fatigue is more important for the quality of life than pain, nausea or depression. Yet these same surveys confirm that oncologists underestimate the importance of cancer related fatigue. This may be partly because patients often do not fully share the full nature of their concerns. When patients do raise the issue of fatigue, the physicians' recommendations are often non specific. However, recent research has shown that fatigue is not inevitable and untreatable, but a symptom amenable to differential diagnosis and specific intervention. Like pain, fatigue is intrinsically a subjective problem where the doctor relies on the patient's reporting. Weakness, exhaustion, lethargy and asthenia are all used as functional descriptions of fatigue. While these are descriptive terms, clinical research in the measurement and alleviation of fatigue requires reproducible measurement tools. Several studies already exist and have begun to explore this important area of symptom management.
Impact of fatigue on quality of life in oncology patients.
Fatigue is the most commonly reported symptom in cancer patients and has a profound effect on patient quality of life (QOL). The Fatigue-1 and Fatigue-2 surveys performed by the Fatigue Coalition have shown that fatigue occurs on a consistent basis in approximately three quarters of patients treated for cancer. Fatigue-2 study results show that fatigue is associated with significant physical, emotional, psychologic, and social consequences, with virtually every aspect of daily life being affected. Patients also report that fatigue interferes with both their own and their caregivers' careers and economic status. Fatigue-2 documented a significant communication gap between patient and physician regarding fatigue and nonspecific physician responses to patient reports. This finding suggests that patients may benefit from physician initiation of discussion of the causes and treatments of fatigue and from physician education regarding available treatment modalities. Additional research is needed to elucidate the nature of fatigue in cancer patients. Algorithms for the differential diagnosis and treatment of cancer fatigue need to be developed and implemented to assist in timely recognition and management.
Impact of cancer-related fatigue on the lives of patients: new findings from the Fatigue Coalition.
PURPOSE: This survey was designed to confirm the prevalence and duration of fatigue in the cancer population and to assess its physical, mental, social, and economic impacts on the lives of patients and caregivers. Patients and Methods. A 25-minute telephone interview was completed with 379 cancer patients having a prior history of chemotherapy. Patients were recruited from a sample of 6, 125 households in the United States identified as having a member with cancer. The median patient age was 62 years, and 79% of respondents were women. Patients reporting fatigue at least a few times a month were asked a series of questions to better describe their fatigue and its impact on quality of life. RESULTS: Seventy-six percent of patients experienced fatigue at least a few days each month during their most recent chemotherapy; 30% experienced fatigue on a daily basis. Ninety-one percent of those who experienced fatigue reported that it prevented a "normal" life, and 88% indicated that fatigue caused an alteration in their daily routine. Fatigue made it more difficult to participate in social activities and perform typical cognitive tasks. Of the 177 patients who were employed, 75% changed their employment status as a result of fatigue. Furthermore, 65% of patients indicated that their fatigue resulted in their caregivers taking at least one day (mean, 4.5 days) off work in a typical month. Physicians were the health care professionals most commonly consulted (79%) to discuss fatigue. Bed rest/ relaxation was the most common treatment recommendation (37%); 40% of patients were not offered any recommendations. CONCLUSIONS: Cancer-related fatigue is common among cancer patients who have received chemotherapy and results in substantial adverse physical, psychosocial, and economic consequences for both patients and caregivers. Given the impact of fatigue, treatment options should be routinely considered in the care of patients with cancer.
The impact of fatigue on patients with cancer: overview of FATIGUE 1 and 2.
Fatigue is a complex, multifactorial disorder with physical, mental, and psychological dimensions that has been associated with diminished quality of life (QOL) in patients with cancer. The prevalence and severity of fatigue, however, has only recently been studied systematically. Two national surveys commissioned by The Fatigue Coalition, a multidisciplinary group of medical practitioners, researchers, and patient advocates, whose mission is to study the importance of fatigue for patients with cancer and their caregivers, have assessed the prevalence, severity, and QOL consequences of fatigue in patients with cancer. The most recent survey, initiated in 1998, sought to confirm and extend observations on the prevalence and impact of fatigue in patients with cancer as part of an initiative to develop guidelines for the differential diagnosis and treatment of fatigue. The FATIGUE 2 study probed the emotional, social, physical, and economic impact of fatigue on patients with cancer and their caregivers. Patient perceptions of the professional response to cancer-related fatigue were also assessed. The key findings of these surveys are reviewed.
The evolving face of palliative care in cancer medicine.
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Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. The Fatigue Coalition.
Although fatigue is the most common symptom reported by cancer patients and has serious adverse effects on quality of life, it remains poorly understood. A survey was designed to characterize the epidemiology of cancer-related fatigue from the perspectives of the patient, primary caregiver, and oncologist. A telephone survey included 419 cancer patients recruited from 100,000 randomly selected households nationwide. Patients provided access to 200 primary caregivers (usually family members) who were also interviewed by telephone. In a separate mail survey, 197 of 600 randomly sampled oncologists (unrelated to the patients) responded to a questionnaire that assessed perceptions and attitudes concerning fatigue in cancer patients who had received chemotherapy or radiotherapy and their caregivers. The median patient age was 65 years, and the principal cancer diagnoses were breast (females) and genitourinary (males). Fifty-nine percent of the patients had received chemotherapy, 63% radiation therapy, and 24% both; 20% of patients received their last treatment within 6 weeks, 31% within 7 weeks to 1 year, and 49% more than 1 year ago. More than three quarters of patients (78%) experienced fatigue (defined as a general feeling of debilitating tiredness or loss of energy) during the course of their disease and treatment. Thirty-two percent experienced fatigue daily, and 32% reported fatigue significantly affected their daily routines. Caregivers reported observing fatigue in 86% of the index patients, and oncologists perceived that 76% of their patients experienced fatigue. Although oncologists believed that pain adversely affected their patients to a greater degree than fatigue (61% v 37%), patients felt that fatigue adversely affected their daily lives more than pain (61% v 19%). Most oncologists (80%) believed fatigue is overlooked or undertreated, and most patients (74%) considered fatigue a symptom to be endured. Fifty percent of patients did not discuss treatment options with their oncologists, and only 27% reported that their oncologists recommended any treatment for fatigue. When used, treatments for fatigue were generally perceived by patients and caregivers to be successful. These data confirm the high prevalence and adverse impact of cancer-related fatigue, although it is seldom discussed and infrequently treated. For patients and oncologists, improving the quality of life of cancer patients requires a heightened awareness of fatigue, a better understanding of its impact, and improve communication and familiarity with interventions that can reduce its debilitating effects.
Issues in antiemetic therapy.
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The use of animal models in cancer drug discovery and development.
The process of searching for new cancer drugs has evolved from rational empiricism using high volume murine screens towards more targeted systems designed to discover agents which are specifically active against the common solid tumors of adulthood. Irrespective of the method of discovery, animal models are necessary in cancer drug development to answer fundamental questions of drug pharmacology and end organ toxicity. This knowledge is fundamental to the design of Phase I clinical trials. Increasingly, animal models are being utilized in the earliest stages of cancer drug discovery, as well as finding new uses guiding dose escalation in man. In addition, transgenic and SCID model systems have special applicability to the preclinical and clinical development of biological agents. This article reviews the emerging roles of animal models in cancer drug discovery and development.
A phase I and pharmacokinetic study of trimetrexate using a 24-hour continuous-injection schedule.
Trimetrexate (TMTX) is an analog of methotrexate and a potent inhibitor of the enzyme dihydrofolate reductase. In this phase I study, TMTX was given intravenously to 32 patients as a constant infusion over 24 hours every 28 days. The maximum-tolerated dose of TMTX was 200 mg/m2, with myelosuppression as the dose-limiting toxicity. Other toxicities included nausea and vomiting, stomatitis, erythema and phlebitis at the site of infusion, rash and skin hyperpigmentation, and elevated serum hepatic enzymes. Two drug-related deaths occurred secondary to leukopenia and sepsis. Twenty-six patients were evaluable for antitumor response. Twenty-one patients had progressive disease, while three patients had disease stabilization. There were two partial responses observed--one in a patient with breast cancer and a second in a patient with nasopharyngeal carcinoma. TMTX pharmacokinetics were studied in 15 patients. The drug had a mean terminal half-life of 13 hours. Steady-state was not achieved during the 24-hour infusions. Only 6% of the parent compound was excreted unchanged in the urine, and CSF levels averaged less than 2% of simultaneously measured plasma levels. A dose of 150 mg/m2 is recommended for phase II trials of TMTX using this 24-hour infusion schedule.
Phase I and clinical pharmacology study of intravenous flavone acetic acid (NSC 347512).
We have conducted a Phase I and pharmacological study of flavone acetic acid, one of a series of novel flavonoids. The drug was administered i.v. weekly for 4 weeks, with a 2-week rest and then repeated. Flavone acetic acid was given initially in a 1-h infusion, but at the 3900-mg/m2 dose level, the infusion time was lengthened to 3 h. A total of 31 patients were treated with 9 different dose levels, ranging from 330 to 6400 mg/m2. Dose-limiting toxicity was acute hypotension that began after about one-third of each drug dose had been infused and rarely lasted more than a few minutes after the infusion was discontinued. In addition, subjective fatigue and asthenia causing unacceptable patient discomfort was dose limiting. A significant side effect noted that was not dose limiting was diarrhea during the infusion. This drug exhibited nonlinear pharmacokinetic behavior. Plasma levels exceeded 300 micrograms/ml during the infusion at the maximally tolerated dose. After the infusion ended the principal half-life was about 2 h. In 24-h urine collections 27% of the flavone acetic acid dose was recovered as intact drug and an additional 37% was recovered as a metabolite. The maximally tolerated dose determined in this study is 6400 mg/m2 given i.v. over 3 h.
Effect of calcium channel blockers on human CFU-GM with cytotoxic drugs.
Calcium channel blockers (CCBs) such as verapamil and nitrendipine are capable of increasing drug sensitivity in resistant murine and human tumor cells. This finding has potential value in the treatment of acquired drug resistance in human malignancies. Thus, we tested the ability of CCBs of two different structural classes to enhance the toxicity of doxorubicin (DOX), vinblastine (VBL), and vincristine (VCR) for normal myeloid and macrophage colony formation (marrow colony forming units-granulocyte-monocyte [CFU-GM]). Drug effects on colony formation from 35 normal volunteer marrows and from seven patient marrows in the recovery phase after cytotoxic chemotherapy were determined. No enhancement of toxicity was mediated by verapamil or nitrendipine when these drugs were co-incubated with the cytotoxic drugs for one hour or 24 hours before plating marrow cells in a semisolid agar system.
Skin reactions induced by trimetrexate, an analog of methotrexate.
We have observed three forms of skin toxicity induced by the new antifol trimetrexate in a Phase I trial. They are: radiation recall, cellulitis at the infusion site, and generalized skin eruptions with erythroderma. A total of 25 episodes of some form of skin reaction occurred in 31 patients. The generalized eruption began about four days after drug administration and cleared within a week. The mechanism of skin toxicity of trimetrexate and other antifols is unknown.
Bone marrow transplantation: current perspectives and future directions.
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Carboplatin for advanced colorectal carcinoma: a phase II study.
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Measuring levels of methotrexate.
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