The neurotoxicity of high-dose cytosine arabinoside is age-related

Gottlieb, David; Bradstock, Kenneth F.; Koutts, Jerry; Robertson, T. I.; Lee, Choon; Castaldi, Peter J.

doi:10.1002/1097-0142(19871001)60:7<1439::aid-cncr2820600705>3.0.co;2-f

Cited by 53 publications

(14 citation statements)

References 9 publications

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“…In conditions of stress, however, the demand for commitment and differentiation may overcome the ability of a reduced stem cell reserve to replicate itself, and marrow failure may ensue. Balducci, Extermann 227 mechanism may be responsible for the increase in the incidence of cardiomyopathy [33] and neurotoxicity [5,34,35]. Table 1 lists the complications of cytotoxic chemotherapy that become more common in older individuals.…”

Section: Susceptibility Of Normal Tissues To the Toxicity Of Antineopmentioning

confidence: 99%

Management of Cancer in the Older Person: A Practical Approach

2000

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The management of cancer in the older aged person is an increasingly common problem. The questions arising from this problem are: Is the patient going to die with cancer or of cancer? Is the patient able to tolerate the stress of antineoplastic therapy? Is the treatment producing more benefits than harm? This article explores a practical, albeit evolving, approach to these questions including a multidimensional assessment of the older person and simple pharmacologic interventions that may ameliorate the toxicity of antineoplastic agents. Age may be construed as a progressive loss of stress tolerance, due to decline in functional reserve of multiple organ systems, high prevalence of comorbid conditions, limited socioeconomic support, reduced cognition, and higher prevalence of depression. Aging is highly individualized: chronologic age may not reflect the functional reserve and life expectancy of an individual. A comprehensive geriatric assessment (CGA) best accounts for the diversities in the geriatric population. The advantages of the CGA include:Recognition of potentially treatable conditions such as depression or malnutrition, that may lessen the tolerance of cancer treatment and be reversed with proper intervention; Assessment of individual functional reserve; Gross estimate of individual life expectancy; and Adoption of a common language to classify older cancer patients. The CGA allows the practitioner to recognize at least three stages of aging:People who are functionally independent and without comorbidity, who are candidates for any form of standard cancer treatment, with the possible exception of bone marrow transplant. People who are frail (dependence in one or more activities of daily living, three or more comorbid conditions, one or more geriatric syndromes), who are a candidate only for palliative treatment; and People in between, who may benefit from some special pharmacological approach, such as reduction in the initial dose of chemotherapy with subsequent does escalations. The pharmacological changes of age include decreased renal excretion of drugs and increased susceptibility to myelosuppression, mucositis, cardiotoxicity and neurotoxicity. Based on these findings, the proposal was made that all persons aged 70 and older, treated with cytotoxic chemotherapy of dose intensity comparable to CHOP, receive prophylactic growth factor treatment, and that the hemoglobin of these patients be maintained >/=12 gm/dl.

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Section: Susceptibility Of Normal Tissues To the Toxicity Of Antineopmentioning

confidence: 99%

Management of Cancer in the Older Person: A Practical Approach

2000

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“…Second, while the mitoxantrone -cytarabine combination used in this study had minimal nonhematological toxicity, it is unlikely that intensification of chemotherapy will prove to be useful. As discussed, substantial escalation of the cytarabine dose is not feasible in the older patient [14]. A German group evaluated the effect of increasing the cytarabine dose from 0.5 g/m 2 to 1 g/m 2 twice daily for a total of 8 doses, in combination with mitoxantrone, in patients older than 60 years with relapsed or refractory AML [25].…”

Section: Discussionmentioning

confidence: 99%

“…High dose cytarabine ( 4 1.5 g/m 2 ) was avoided because of a high risk of severe irreversible neurotoxicity in the elderly [14] and the absence of a beneficial effect of high vs. standard dose cytarabine as induction and/or post-remission chemotherapy in patients over 60 years [15,16]. However, a degree of dose responsiveness with cytarabine had been suggested by a higher CR rate with standard (200 mg/m 2 days 1 -7) vs. low dose (20 mg/m 2 for 21 days) cytarabine in elderly patients [7].…”

Section: Introductionmentioning

confidence: 99%

Prognostic features for response and survival in elderly patients withde novoacute myeloid leukemia treated with mitoxantrone and intermediate dose cytarabine

Grigg¹,

Reynolds²,

McQuillan³

et al. 2005

Leukemia & Lymphoma

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Forty-three fit elderly patients with de novo acute myeloid leukemia (AML) received chemotherapy with mitoxantrone and intermediate dose cytarabine (MIDAC) in a phase II clinical trial conducted by the Australasian Leukaemia and Lymphoma Group. The main aim of the study was to evaluate the tolerability and efficacy of MIDAC in inducing durable remissions. While the chemotherapy was generally well tolerated, less than half the patients achieved complete remission (CR) after induction and many of those in CR could not receive planned consolidation cycles. The median overall survival for all patients was 6.5 months and the median disease-free survival for those achieving CR was 8.3 months. Only 2 patients survived beyond 4 years. Factors significantly associated with shorter survival were adverse cytogenetics, marrow dysplasia and increasing age. These results suggest that only selected elderly patients with AML are likely to benefit from aggressive chemotherapy and that novel therapies are required to improve the poor prognosis of this group.

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“…Generally, cerebellar toxicity has been noted only with high-dose (> 1 g/ m 2 ) intravenous administration [60••,61,62,64••]. Risk factors other than dose include age (patients aged over 50 years at higher risk), cumulative dose, and renal dysfunction resulting in impaired drug clearance [61,65,66]. The estimated incidence of cerebellar dysfunction with highdose ara-C is between 8% and 20%, and it is often reversible.…”

Section: Cerebellar Dysfunctionmentioning

confidence: 99%

Central nervous system toxicity from cancer treatment

Armstrong

Gilbert

2004

Curr Oncol Rep

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Neurologic complications of cancer therapy are an increasingly important concern in patient management. Improvements in systemic therapies and increasing use of local treatments to target such specific tumor sites as brain or leptomeningeal metastases have resulted in increased incidence of treatment toxicity in the central nervous system (CNS). Recognition of specific treatment-related toxicities, and more importantly, differentiation of treatment toxicity from reversible causes of neurologic dysfunction, are critical. This article reviews the evaluation and treatment of major CNS toxicities related to cancer treatment and conditions that present with similar signs and symptoms. The three most common of these, alterations in cognition and consciousness, seizures, and cerebellar dysfunction, are discussed. Prompt recognition of these problems and their causes will have an impact on patient care in all areas of oncology.

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The neurotoxicity of high-dose cytosine arabinoside is age-related

Cited by 53 publications

References 9 publications

Management of Cancer in the Older Person: A Practical Approach

Management of Cancer in the Older Person: A Practical Approach

Prognostic features for response and survival in elderly patients withde novoacute myeloid leukemia treated with mitoxantrone and intermediate dose cytarabine

Central nervous system toxicity from cancer treatment

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