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P Forsyth

Publications and source records attributed to P Forsyth.

24 records · Page 2Linked to original sources

Phase II trial of docetaxel in patients with recurrent malignant glioma: a study of the National Cancer Institute of Canada Clinical Trials Group.

BACKGROUND: We conducted a phase II study to determine the response to, and toxicity of, docetaxel (Taxotere; Rhône Poulenc Rorer Pharmaceuticals, Inc) in patients with recurrent malignant glioma. PATIENTS AND METHODS: Eighteen patients with recurrent malignant glioma were treated with 100 mg/m2 (no prior chemotherapy) or 75 mg/m2 (prior adjuvant chemotherapy) of docetaxel intravenously over 1 hour, every 3 weeks. Premedication with dexamethasone, diphenhydramine and ranitidine or cimetidine was given to all patients. Five (28%) had gioblastoma multiforme (GBM) and the rest other malignant gliomas. Eleven (61%) had an ECOG performance status of 0 or 1, and 13 (72%) were on corticosteroids at the start of treatment. Rigorous response criteria were used. All were eligible and evaluable for response. RESULTS: No complete or partial responses were observed; the objective response rate was 0% (95% confidence interval: 0-15.3%). Patients received a median of 2 cycles (range, 1-6). Grade 3 or 4 neutropenia occurred in 17 (94%) patients and was associated with fever that required intravenous antibiotics in 4 (22%) patients. An additional patient received intravenous antibiotics for an infection not associated with neutropenia. Six (33%) patients had mild hypersensitivity reactions. Onychodystrophy, peripheral edema and peripheral neuropathy were uncommon and mild. CONCLUSIONS: Docetaxel has no significant activity in patients with recurrent malignant glioma.

Adult↗

Phase II study of topotecan in patients with recurrent malignant glioma. National Clinical Institute of Canada Clinical Trials Group.

BACKGROUND: The NCIC Clinical Trial Group has an ongoing interest in assessing investigational agents in minimally pretreated patients with malignant glioma. Topotecan is one of the first topoisomerase I inhibitors to enter clinical trials and has shown early evidence of activity in several solid tumors. We have conducted a phase II trial of topotecan in patients with malignant glioma. METHODS: Adults with malignant glioma and recurrent contrast enhancing measurable disease (> or = 2 x 2 cm) were eligible. Topotecan 1.5 mg/m2 i.v. was given daily x five days every three weeks. Response and toxic effects were assessed at the end of each cycle. RESULTS: Thirty-one patients were entered onto the study: fifteen had glioblastoma, 16 anaplastic astrocytoma, all had prior radiation, 15 prior chemotherapy, and all were assessable for response and toxicity. Two patients (6%) responded: one had a complete radiographic response, but died with neutropenic sepsis, and the second had a prolonged partial response (> 97 weeks). Twenty-one patients (68%) had stable disease for five to 86 + weeks (median 19) and eight (26%) had progressive disease after one cycle. Toxicity was primarily hematologic; 18 (58%) had grade 4 neutropenia (< 0.5 x 10(9)/1), usually brief, and three (10%) grade 4 thrombocytopenia (< 25 x 10(9)/1). Twelve of 109 cycles (11%) were given at reduced dose. CONCLUSIONS: Topotecan in this dose and schedule has only modest activity in recurrent glioblastoma and anaplastic astrocytoma.

Adult↗

Salvage chemotherapy for oligodendroglioma.

The authors present their experience with salvage chemotherapy for oligodendroglioma, an uncommon brain tumor that responds predictably to PCV (procarbazine, lomustine (CCNU), and vincristine) when given as initial therapy. The authors reviewed the records of patients with oligodendrogliomas who received a second, third, or fourth cytotoxic regimen prescribed to combat tumor recurrence documented by computerized tomography or magnetic resonance imaging following an initial chemotherapy program. Initial regimens were prescribed at various time points: as neoadjuvant therapy prior to radiotherapy, as adjuvant therapy in conjunction with radiotherapy, or at recurrence following radiotherapy. Response criteria were based on measurable changes in tumor size following published guidelines. Twenty-three patients (14 men and nine women) aged 25 to 58 years (median 36 years) received 33 salvage regimens. When non-PCV chemotherapy had been the prior regimen, seven (88%) of eight patients responded to salvage chemotherapy, all seven (100%) responding to PCV. Administration of PCV was effective after regimens of carmustine and CCNU but was ineffective after prior administration of PCV. When PCV had been given any time previously, only four (19%) of 21 patients responded to salvage chemotherapy; however, four (40%) of 10 patients who received etoposide (VP-16)/cisplatin (CDDP) responded. Despite the small number of patients, two noteworthy trends emerge from these data: first, PCV is a highly effective salvage treatment when used at tumor recurrence following non-PCV chemotherapy regimens, and second, the synergistic combination of VP-16 and CDDP may exert substantial anti-oligodendroglioma activity, and it warrants further evaluation.

Adult↗

Interocular transfer in the split-brain rat.

After the 1991 development of a method to transect the optic chiasm in the rat, the authors investigated interocular transfer in split-chiasm rats with corpus callosum section and callosum intact. Rats were monocularly trained on an orientation discrimination, reversed with the other eye, and retrained with the 1st eye on the 2nd-eye problem or reversal. In split-chiasm rats, the 2nd-eye S+ (correct stimulus) showed strong transfer (55% savings) to the 1st eye. S- (incorrect stimulus) did not; reversal and transfer groups differed significantly. Split-brain rats retrained with the 1st eye on the 2nd eye S+ required no more trials than original learning, as if they had not experienced this problem. Split-brain rats retested with the original S+ showed modest (19%) savings. The findings establish interhemispheric communication via the callosum and suggest, as in findings of cat and monkey studies, the disruption of transfer by callosal section.

Animals↗

A letter from Romania.

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Acquired Immunodeficiency Syndrome↗

The effects of proglumide on cholecystokinin-, bombesin-, and glucagon-induced satiety in the rat.

Intraperitoneal (IP) administration of the glutaramic acid derivative proglumide inhibited satiety induced by all IP doses of cholecystokinin octapeptide (CCK-OP) in 3-hour food-deprived intact rats. Proglumide did not influence satiety when administered alone and did not inhibit satiety induced by IP glucagon. While proglumide did not inhibit satiety induced by low doses of IP bombesin, it partially and significantly inhibited the satiety effects produced by high doses of this peptide. Since bombesin is a known secretagogue for CCK in several species, these results indicate that while bombesin and CCK act independently to induce satiety, the effect induced by high doses of bombesin is mediated, in part, by the release of endogenous CCK or a structurally related peptide. Furthermore, these results illustrate that proglumide is a specific antagonist of CCK-induced satiety and is, therefore, a potentially useful tool for investigating the physiologic role of this peptide in the control of food intake.

Animals↗