International journal of radiation oncology, biology, physics
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Int. J. Radiat. Oncol. Biol. Phys. · Sep 1984
Randomized Controlled Trial Comparative Study Clinical TrialMisonidazole combined with hyperfractionation in the management of malignant glioma.
Multiple daily fractionated radiation therapy (MDF) may be more effective than conventionally fractionated radiation therapy (CF) in the treatment of malignant glioma. The hypoxic cell sensitizer misonidazole (MISO) could be more effective when employed with small fractions of radiation every 4 hours to take advantage of the long half-life of the drug. To evaluate MDF and MDF in combination with MISO, a randomized prospective trial was initiated. ⋯ The addition of MISO to MDF did not result in further improvement in survival. Acute toxicity was acceptable. No clinically apparent delayed toxicity was observed.
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Int. J. Radiat. Oncol. Biol. Phys. · Sep 1984
Randomized Controlled Trial Clinical TrialMisonidazole and irradiation in the treatment of high-grade astrocytomas: further report of the Vienna Study Group.
A randomized study investigating the value of misonidazole in patients irradiated for grade III and IV supratentorial astrocytomas was started in June 1977. With a minimum follow-up time of 6 months, 45 patients who completed therapy are available for analysis. All patients received the same radiation treatment (66.5 Gy in 31 fractions over 7.5 weeks, field size reduction after 45 Gy). ⋯ There are no significant differences in Karnofsky performance status, sex and in histological grade or in age distribution between the groups. However, the type of surgery (complete or subtotal) influenced survival markedly: patients with complete surgery lived significantly longer (p less than 0.0009). Neurotoxic side effects of misonidazole were minimal.
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Int. J. Radiat. Oncol. Biol. Phys. · Sep 1984
Randomized Controlled Trial Clinical TrialNeuropathy of nitroimidazole radiosensitizers: clinical and pathological description.
The dose limiting toxicity of the nitroimidazole radiosensitizers is peripherial neuropathy. Improved pharmacology of newer drugs has eliminated the encephalopathy. Peripheral neuropathies are predominently mild to moderate paresthesias of both hands and feet. ⋯ Sural nerve biopsies from patients indicate progressive axonal degeneration affecting both large and small caliber myelinated fibers. Axonal damage appears to be more severe in the distal portion of the nerves. More data are needed for correlation of clinical and pathological changes.
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Int. J. Radiat. Oncol. Biol. Phys. · Sep 1984
Clinical TrialIs misonidazole neurotoxicity altered by the use of phenytoin and/or dexamethasone in RTOG 79-18 and RTOG 79-16?
An analysis of Misonidazole (MISO) neurotoxicity in RTOG 79-16 and RTOG 79-18 was undertaken to evaluate the incidence of neurotoxicity relative to dexamethasone dose and phenytoin use. MISO was administered as follows: 79-16 arm A, 1 gm/m2 5 days a week for a total of 10 gm/m2 in 2 weeks; 79-16 arm B, 2 gm/m2 twice weekly for a total of 12 gm/m2 in 3 weeks; and 79-18, 2.5 gm/m2 once a week for a total of 15 gm/m2 in 6 weeks. Practically all patients were on dexamethasone, and 240 out of 550 were on phenytoin for seizures. ⋯ There was no correlation between dexamethasone dose and incidence of neurotoxicity within each study. However, the incidence of (PN) for the combined studies was 6.4% (35/550) which is lower than 18.9% (85/449) for non-brain Phase III protocols where patients are rarely, if ever, on dexamethasone or other corticosteroids. Four hour and 24 hour plasma MISO levels, and 24 hour/4 hour MISO ratios did not correlate with toxicity.
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Int. J. Radiat. Oncol. Biol. Phys. · Sep 1984
Clinical Trial Controlled Clinical TrialMisonidazole with dexamethasone rescue: an escalating dose toxicity study.
Neurotoxicity induced by misonidazole (MISO) and desmethylmisonidazole (DMM) has become the dose limiting factor in clinical work. In 1981, we reported a preliminary study suggestive that Dexamethasone (DEXA) does have a protective effect against peripheral neuropathies (PN) resulting from toxicity of misonidazole. Furthermore, in that study we have observed that DEXA did not alter the plasma pharmacokinetics of misonidazole. ⋯ One grade I PN occurred in the first four patients receiving 15.5 gm/M2. Six additional patients were entered at this dose level and no further incidence of PN was observed. Patients are being entered at the next step of 17.5 gm/M2.