Glioblastoma multiforme: Treatment by large dose fraction irradiation and metronidazole

Kapp, Daniel S.; Wagner, Franklin C.; Lawrence, R. F.

doi:10.1016/0360-3016(82)90638-1

Cited by 31 publications

(6 citation statements)

References 12 publications

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“…There is abundant evidence that these tumors are not curable by presently available postoperative radiotherapeutic technics. In an attempt to improve the therapeutic ratio, a hypofractionated schedule has been proposed in many centers [13][14][15][16][17][18][19].…”

Section: Discussionmentioning

confidence: 99%

Postoperative hypofractionated radiotherapy versus conventionally fractionated radiotherapy in malignant gliomas. A preliminary report on a randomized trial

Gliński

1993

J Neuro-Oncol

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A prospective randomized study of 108 patients with cerebral malignant gliomas was carried out at the Department of Radiation Oncology of Maria Sklodowska-Curie Memorial Center in Kraków. 44 patients with histologically proven glioblastoma multiforme and 64 patients with anaplastic astrocytoma received postoperative radiotherapy. Patients were randomized to two treatment arms: Conventionally Fractionated Radiotherapy (CFR) and Hypofractionated Radiotherapy (HF). In the CFR group, the whole brain was irradiated to the total dose of 50 Gy in 25 fractions over 5 weeks, then a 10 Gy 'boost' in 5 fractions in 5 days was delivered to the site of the primary lesion. In the HF group, there were 3 courses of irradiation separated by a one month interval. In each of the two first series the patients received 20 Gy in 5 fractions in 5 days to the whole brain, and in the third course, 10 Gy 'boost' in 5 days was delivered as in the CFR regimen. The tolerance to treatment has been found to be good in both groups. The 2-year actuarial survival rate for patients with anaplastic astrocytoma was 22% for CFR and 18% for HF. Patients with glioblastoma multiforme treated with HF had a better prognosis in comparison to the CFR group with the two-year actuarial survival rates being 23% and 10%, respectively. This difference is statistically significant at the 0.05 level.

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Section: Discussionmentioning

confidence: 99%

Postoperative hypofractionated radiotherapy versus conventionally fractionated radiotherapy in malignant gliomas. A preliminary report on a randomized trial

Gliński

1993

J Neuro-Oncol

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“…In humans nimorazole has been given in doses up to 25 g in 10 days without causing peripheral neuropathy or other severe side effects (Overgaard et al, 1983). Thus nimorazole seems to be considerably better tolerated than MISO, and on the basis of largeanimal toxicity it may be tolerated as well as metronidazole (Flagyl) which can be given in daily doses of 6 g/m2 and in total doses up to 100 g (Kapp et al, 1982;Karim, 1978;Urtasun et al, 1975). Therefore it is likely that nimorazole could be given in normal radiation fractionation schedules in doses corresponding to those necessary to produce ERs of 1-4 in the present tumour after single-dose radiation in air.…”

Section: I)iscussionmentioning

confidence: 99%

A comparative investigation of nimorazole and misonidazole as hypoxic radiosensitizers in a C3H mammary carcinoma in vivo

Overgaard¹,

Overgaard²,

Os³

et al. 1982

Br J Cancer

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“…Experience from large animal toxicity studies (Farmitalia, Carlo Erba, unpublished observations) suggests that nimorazole may be even better tolerated than metronidazole (Flagyl) which itself can be administrated in daily doses of 6 gm-2 up to a total of 100 g, although such high doses may be associated with significant gastrointestinal toxicity and some central and peripheral neuropathy (Kapp et al, 1982;Karim, 1978;Urtasun et al, 1975Urtasun et al, , 1982. If the lack of significant toxicity is confirmed, it may be possible to give nimorazole in conjunction with conventional daily radiation fractionation schedules at a dose level which may enhance the radiation response of hypoxic cells by a factor of -1.4.…”

mentioning

confidence: 99%

Studies of the pharmacokinetic properties of nimorazole

Overgaard¹,

Overgaard²,

Timothy³

1983

Br J Cancer

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The pharmacokinetics of the hypoxic radio-sensitizer nimorazole were studied in 19 individuals after single oral doses of between 0.5-3.5 g. HPLC measurements showed, after a rapid absorption, a linear relationship between peak plasma concentration and given dose. Mean elimination half life was 3.1 h. A tendency to a dose-dependent variation in the apparent volume of distribution, total body clearance and elimination half life suggest non-linear pharmacokinetics of nimorazole. Tumour concentrations measured in 5 patients gave tumour/plasma ratios between 0.8-1.3. No toxicity was observed. The results indicate that nimorazole may have potential as a clinically useful hypoxic radiosensitizer.

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Glioblastoma multiforme: Treatment by large dose fraction irradiation and metronidazole

Cited by 31 publications

References 12 publications

Postoperative hypofractionated radiotherapy versus conventionally fractionated radiotherapy in malignant gliomas. A preliminary report on a randomized trial

Postoperative hypofractionated radiotherapy versus conventionally fractionated radiotherapy in malignant gliomas. A preliminary report on a randomized trial

A comparative investigation of nimorazole and misonidazole as hypoxic radiosensitizers in a C3H mammary carcinoma in vivo

Studies of the pharmacokinetic properties of nimorazole

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