Cancer Chemotherapeutic Agents

Karnofsky, David A.

doi:10.3322/canjclin.11.2.58

Cited by 70 publications

(83 citation statements)

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“…Inhibition of RNA produced by Ara-C and 6-MP support the evid ence that possible sites of action of these drugs may lie in the RNA bio synthetic pathway [4][5][6].…”

Section: Discussionsupporting

confidence: 56%

A Micro-system for Screening Anti-leukemic Drugs Utilizing Human Whole Blood

Farrow¹,

Dyke²

1971

Chemotherapy

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A primary drug-screening system has been developed that can be used as a fast, operationally efficient, simple, quantitative and reliable method for testing the effects of chemotherapeutic drugs on nucleic acids of leukocytes in human-peripheral whole blood. The stimulation of division of lymphocytes by phytohemagglutinin in normal and leukemic blood provided the modus operandi of incorporation by ³H-thymidine into DNA and ³H-uridine into RNA. The inhibition of incorporation of these radio-activite precursors was measured relative to control samples without drug, and a comparison was made between the ability of the drugs to inhibit this incorporation into leukocytes of normal blood and of various types of leukemia. Three drugs, quinacrine, cytosine arabinoside and 6-mercapto-purine were tested in this system in concentrations ranging from 10^-8–10^-4 m.

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“…Inhibition of RNA produced by Ara-C and 6-MP support the evid ence that possible sites of action of these drugs may lie in the RNA bio synthetic pathway [4][5][6].…”

Section: Discussionsupporting

confidence: 56%

A Micro-system for Screening Anti-leukemic Drugs Utilizing Human Whole Blood

Farrow¹,

Dyke²

1971

Chemotherapy

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“…Eligibility criteria were similar to those commonly employed in other trials of advanced CNS tumors [23–29]. We included adults aged 21 years or over with histologically proven RMBTs defined as either 1) malignant (WHO III–IV) gliomas progressive after a radiation-containing initial therapy or 2) stage IV parenchymal metastases from systemic malignancies.…”

Section: Methodsmentioning

confidence: 99%

Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors

et al. 2013

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Summary Background Recurrent malignant brain tumors (RMBTs) carry a poor prognosis. Dichloroacetate (DCA) activates mitochondrial oxidative metabolism and has shown activity against several human cancers. Design We conducted an open-label study of oral DCA in 15 adults with recurrent WHO grade III – IV gliomas or metastases from a primary cancer outside the central nervous system. The primary objective was detection of a dose limiting toxicity for RMBTs at 4 weeks of treatment, defined as any grade 4 or 5 toxicity, or grade 3 toxicity directly attributable to DCA, based on the National Cancer Institute’s Common Toxicity Criteria for Adverse Events, version 4.0. Secondary objectives involved safety, tolerability and hypothesis-generating data on disease status. Dosing was based on haplotype variation in glutathione transferase zeta 1/maleylacetoacetate isomerase (GSTZ1/MAAI), which participates in DCA and tyrosine catabolism. Results Eight patients completed at least 1 four week cycle. During this time, no dose-limiting toxicities occurred. No patient withdrew because of lack of tolerance to DCA, although 2 subjects experienced grade 0–1 distal parasthesias that led to elective withdrawal and/or dose-adjustment. All subjects completing at least 1 four week cycle remained clinically stable during this time and remained on DCA for an average of 75.5 days (range 26–312). Conclusions Chronic, oral DCA is feasible and well-tolerated in patients with recurrent malignant gliomas and other tumors metastatic to the brain using the dose range established for metabolic diseases. The importance of genetic-based dosing is confirmed and should be incorporated into future trials of chronic DCA administration.

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“…The KPS, 12) a measure of preoperative function, has scores of 0–100: a score of 100 indicates full, independent performance; ≥80, normal level of activity; 50–70, living at home with assistance; and 0, death. The ASA system is used to assess a patient’s fitness for surgery, as follows: class I indicates good health; II, mild systemic disease; III, severe systemic disease; IV, severe, systemic, life-threatening disease; V, a moribund patient who is not expected to survive without surgery; and VI, a patient who has been declared brain dead and whose organs are being removed for donor purposes.…”

Section: Introductionmentioning

confidence: 99%

Review of Current Evidence Regarding Surgery in Elderly Patients with Meningioma

Ikawa

Kinoshita

Takeda

et al. 2017

Neurol. Med. Chir.(Tokyo)

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The Japanese population features the highest rate of elderly individuals worldwide. Moreover, Japan has the highest number of computed tomography/magnetic resonance imaging devices in the world, which has led to an increase in the incidental detection of meningioma in healthy elderly patients. Many previous papers have discussed the risks and indications for surgery in this patient population, but available information remains insufficient, and the definition of “elderly” has not been standardized. This review tried to clarify the published evidence and challenges associated with elderly meningioma based on a search of the PubMed database using the terms “meningioma,” “elderly,” and “surgery” for English-language clinical studies and collected related papers published from 2000 to 2016. Twenty-four papers were reviewed and classified by definition of elderly age: over 60, 65, 70, and 80 years old. Six of seven papers that defined the elderly cutoff as over 65 years old were published after 2010, which suggested the consensus definition. Four preoperative grading scoring systems were described and associated with mortality. The 1-year and 5-year mortality rates ranged from 0% to 16.7% and from 7% to 27%, which were comparable with unselected cohorts. Review of risk factor analysis emphasized the importance of considering the preoperative status, presence of comorbidities, and optimum surgical timing during patient selection. Careful choice of patients can also lead to better quality of life. A prospective randomized study considering patient frailty should address the causes and prevention of complications.

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Cancer Chemotherapeutic Agents

Cited by 70 publications

References 0 publications

A Micro-system for Screening Anti-leukemic Drugs Utilizing Human Whole Blood

A Micro-system for Screening Anti-leukemic Drugs Utilizing Human Whole Blood

Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors

Review of Current Evidence Regarding Surgery in Elderly Patients with Meningioma

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