Intratumor administration of beta-interferon in recurrent malignant gliomas: a phase I clinical and laboratory study

Article Abstract:

Patients with malignant glioma, a tumor affecting the glia cells that form the supporting tissue of the nervous system, have a very poor prognosis. In addition, the available chemotherapeutic agents may produce serious toxicity in the brain and retina. For these reasons, considerable attention has been paid to biological response modifiers, a loosely related class of pharmacological compounds that affect cell growth and act upon the immune system. Among these compounds is beta-interferon, which has been shown to have some antitumor activity in both tissue culture experiments and in patients. Although beta-interferon causes side effects such as fatigue, fever, chills, and myalgia when administered systemically, it is well tolerated when injected directly into the tumor itself. In order to determine patient tolerance to beta-serine-interferon, doses from 5 to 180 million units were administered to 20 patients with recurrent glioma. The interferon was administered through an Ommaya brand reservoir which was implanted with its catheter tip in the center of the tumor cavity after surgical removal of the bulk of glioma. All 20 patients have died, but 12 lived long enough for evaluation. Of those 12, 3 had their disease stabilized for 5 to 18 months. There was no correlation between the interferon dose and survival. Since all patients also received radiotherapy and six had received chemotherapy, few conclusions can be drawn about the efficacy of interferon. It can be stated, however, that even the maximum dose used in this study was well tolerated by the patients. The Ommaya reservoir, which functions well when used to administer drugs directly into the cerebrospinal fluid, had a tendency to clog when implanted into a tumor bed. Obstruction of the catheter or infection occurred in 30 percent of the patients in this study. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Gliomas, Interferon beta

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A Phase I study of 4'-O-tetrahydropyranyladriamycin: clinical pharmacology and pharmacokinetics

Article Abstract:

Pirarubicin is a synthetic analogue of doxorubicin (Adriamycin). The substance shows promise as a new anticancer agent. Fewer cell lines appear to be resistance to pirarubicin compared with doxorubicin. Furthermore, the side effects of pirarubicin seem to be no greater than that of doxorubicin. Toxicity to the heart is the most serious side effect of doxorubicin, and this particular side effect seems to be less serious with pirarubicin. As a part of a Phase I study of pirarubicin in treating cancer, researchers evaluated the uptake and metabolism of pirarubicin to determine the optimal dose range for use in further tests of the drug. The investigators found that the dose-limiting side effect of pirarubicin was a reduction in granulocytes in the blood, which may be life-threatening with higher doses of the drug. Monitoring of heart function showed a dose-dependent decrease in the left-ventricular ejection fraction, which suggests that the drug may be different from its parent doxorubicin. The cardiotoxicity of doxorubicin does not appear to be dose dependent, but is abrupt after the cumulative dose crosses a threshold. Unfortunately, the present study was not large enough to fully compare the cardiotoxicity of the two drugs. Pirarubicin disappears from the blood significantly more rapidly than doxorubicin, which may result from increased uptake of the compound by tumor cells and blood cells. The analysis of the metabolites of pirarubicin revealed that doxorubicin constitutes less than 10 percent of the various metabolites, which suggests that pirarubicin is an independent anticancer agent and is not merely degraded into doxorubicin in the body. Both drugs seem to work by a similar mechanism, however; pirarubicin and doxorubicin interfere with cellular replication by inducing breaks in DNA strands. (Consumer Summary produced by Reliance Medical Information, Inc.)

Physiological aspects, Anthracyclines, Dosage and administration, Antineoplastic antibiotics

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"Eight-drugs-in-one-day" chemotherapy administered before and after radiotherapy to adult patients with malignant gliomas

Article Abstract:

Patients with malignant astrocytomas, i.e. glioblastoma multiforme and anaplastic astrocytoma (cancers involving nerve cells), have a median survival time that rarely surpasses 50 weeks. The standard treatment, which consists of radiotherapy and carmustine (BCNU), provides survival rates of about 30 percent at 18 months; this is the standard against which many experimental protocols are measured. Preliminary work in children with malignant gliomas and medulloblastomas has suggested some benefits may be derived from a chemotherapeutic program consisting of eight drugs. To determine if a similar program might be beneficial for adults, 31 previously untreated patients were placed on an 'eight-drugs-in-one-day' chemotherapeutic program. The patients were given methylprednisolone, vincristine, lomustine, procarbazine, hydroxyurea, cytosine arabinoside, dacarbazine, and cisplatin over an intricate 18-hour schedule. The chemotherapy began no more than two weeks after the surgery which histologically confirmed the malignant glioma. Patients received two cycles of chemotherapy prior to radiotherapy, and eight additional cycles were planned. Most patients received fewer than eight cycles due to tumor progression and treatment toxicity. Bone-marrow suppression was common; 16 patients developed infections requiring treatment; two of these infections were life-threatening. Four patients developed neuropathy (nerve disease), and five developed thrombophlebitis (inflammation and blockage of a vein). The survival rate was similar to other chemotherapeutic protocols. Because other protocols are less toxic, it was concluded that the 'eight-drugs-in-one-day' regimen offers no benefit to these patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Brain cancer, Astrocytoma, Astrocytomas

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