Uptake of bleomycin by human brain tumours

Hayakawa, Tõru; Ushio, Yukitaka; Morimoto, Kazuyoshi; Hasegawa, Hiroko; Mogami, Heitaro; Horibata, Kenkichi

doi:10.1136/jnnp.39.4.341

Cited by 23 publications

(3 citation statements)

References 8 publications

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“…Hayakawa injected Bleomycin at a dose of 1 mg/kg of body weight intravenously in patients with various types of brain tumors prior to surgery (14). Tumor specimens were then analyzed for Bleomycin content and compared to the level of Bleomycin contained in the surrounding brain.…”

Section: Discussionmentioning

confidence: 99%

Bleomycin and brain tumors

et al. 1983

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A logical inference from the recent reports indicating that malignant brain tumors are composed of a heterogeneous cell population is that combination chemotherapy will be required for effective brain tumor control. For several years we have been investigating the use of Bleomycin as an agent to be used in conjunction with radiation therapy and a nitrosourea compound. Since systemically administered Bleomycin does not cross the blood-brain-barrier and has significant toxicity when used parenterally in high doses, we have studied the use of smaller doses of Bleomycin injected directly into the brain tumor cavity. Such an intracerebral dose was more effective in prolonging survival of rats burdened with experimental 9L gliosarcomas than an intravenous dose that is 25 times as great. The combination of intracerebrally administered Bleomycin and radiation therapy was more effective than either modality alone. Furthermore, the combination of Bleomycin delivered intracerebrally and BCNU given systemically was more effective than either agent used alone. Finally, in a Phase I clinical of Bleomycin given via an Ommaya reservoir to eight patients with recurrent malignant brain tumors, we have demonstrated that individual doses of up to 7.5 units and cumulative doses of up to 255 units can be administered without significant toxicity.

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Section: Discussionmentioning

confidence: 99%

Bleomycin and brain tumors

et al. 1983

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“…One may argue against the relevance of the experiments on subcutaneous glioma to glioma in the human brain. But, because the permeability of bloodbrain barrier is altered the drug has been detected in the human brain tumor after iv injection [21], the transfer of the therapy drug from the blood could be similar.…”

Section: Discussionmentioning

confidence: 99%

Use of ¹¹¹in‐bleomycin for combining radiotherapy and chemotherapy on glioma‐bearing mice

Hou

Hoch

Johnston

et al. 1985

Journal of Surgical Oncology

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Mice bearing transplanted glioma received 0.9% NaCl, 0.1 mg of BLM, or 200-250 microCi of 111In-BLM (0.1 mg BLM) daily for 5 days intraperitoneally. After therapy, tumor sizes were in the order NaCl greater than BLM greater than 111In-BLM. On the 11th day after the first injection, tumor size (mm3) in the 111In-BLM group was 1,220; in the BLM group, it was 2,310 (P less than .025). After intratumor injection of a total dose of 0.1 mg of BLM/gm tumor weight, or of 1 mCi/gm tumor weight of 111In-BLM (carried by 0.1 mg of BLM/gm tumor weight), the tumor size decreased in the 111In-BLM group more than in the BLM group. On the 5th day after the 2nd dose therapy, the tumor size in the 111In-BLM group was 2,020; in the BLM group it was 4,220 (P less than .05). Host weights for these two groups were similar. The necrotic area in the tumor was much greater in the 111In-BLM group than in the BLM group. These results suggest the use for radiotherapy and chemotherapy.

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“…The cell kinetics of target tissues have also been included (Zaharko et al, 1974;Dagnino et al, 1979). Few studies have been made in man to collect data on drug concentrations in accessible extravascular compartments such as CSF, exudates, surgical specimens, etc (Evans and Pratt, 1978;Hayakawa et al, 1976).…”

Section: Anticancer Drugsmentioning

confidence: 99%

Clinical Relevance of Pharmacokinetics

Tognoni

Bellantuono

Bonati

et al. 1980

Clinical Pharmacokinetics

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The importance of a more therapeutically oriented perspective for pharmacokinetics has been repeatedly advocated and stressed during the past few years. ReView of recent publications in this field reveals that the search for solutions to clinically relevant problems is merely a secondary goal in many studies. Hence, to obtain reliable information which can be applied safely in therapeutic practice. studies need to be interpreted critically. After careful analysis of publications on some of the most representative drugs and drug groups (anti-infective agents, antiepileptic drugs, psychotherapeutic drugs, antiarrhythmic agents, digoxin, propranolol, theophylline, warfarin, anticancer agents), tentative guidelines are given for datafor which the clinical relevance is well established, for findings for which the relevance should be checked in routine practice, for areas where much research is still needed before kinetic knowledge can result in improved therapeutic outcome, and for fields where only minor therapeutic advances can be expected fro,!, extended kinetic investigations. Within the general framework of clinical pharmacology, it appears that the use of pharmacokinetics is a fundamental research tool and a useful aid to therapeutic practice only if its limitations are clearly recognised, and if priority is given to creating favourable, controlled conditions for good diagnostic practice, general patient care and compliance of the patient with treatment. A restricted attitude is suggested toward the natural expansion of blood level monitoring, because of the risk that doctors and institutions become 'dependent' on this technique and 10lie their critical capacity in the use of both clinical and kinetic data.

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Uptake of bleomycin by human brain tumours

Cited by 23 publications

References 8 publications

Bleomycin and brain tumors

Bleomycin and brain tumors

Use of ¹¹¹in‐bleomycin for combining radiotherapy and chemotherapy on glioma‐bearing mice

Clinical Relevance of Pharmacokinetics

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Uptake of bleomycin by human brain tumours

Cited by 23 publications

References 8 publications

Bleomycin and brain tumors

Bleomycin and brain tumors

Use of 111in‐bleomycin for combining radiotherapy and chemotherapy on glioma‐bearing mice

Clinical Relevance of Pharmacokinetics

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Use of ¹¹¹in‐bleomycin for combining radiotherapy and chemotherapy on glioma‐bearing mice