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Biomedical subjects

G T Budd

Publications and source records attributed to G T Budd.

78 records · Page 5Linked to original sources

Treatment of advanced ovarian cancer with cisplatin, adriamycin, and cyclophosphamide: effect of treatment and incidence of intracranial metastases.

A retrospective analysis of 42 patients with stage III, IV, or recurrent epithelial ovarian carcinoma treated with monthly cisplatin, Adriamycin, and cyclophosphamide (PAC) was made. Of 36 patients with measurable disease, 18 (50%) achieved a clinical complete response (CR) and 12 (33%) achieved a partial response (PR) for an objective response rate of 83%. Six stage III patients remained without measurable disease after surgery and postoperative PAC and are included in the survival data. The median survival of all patients was 22 months (10 months for nonresponders), with a median duration of response of 15 months (19+ months for clinical complete responders). Of 16 patients who underwent second-look laparotomy while in clinical CR, 8 were pathologically free of disease. Of these 8 surgically staged CRs, 2 have suffered CNS relapses, while the rest remain free of disease. One additional patient, who had been found to have only microscopic disease at the time of second-look surgery, subsequently relapsed in the CNS, for a total of 3 patients with CNS relapse. We conclude that PAC is an effective regimen, but that prolonged survival of these patients may put them at greater risk for CNS relapse.

Adult↗

Phase I/II trial of human recombinant granulocyte-colony-stimulating factor (filgrastim) and escalating doses of cyclophosphamide, mitoxantrone, and 5-FU in the treatment of advanced breast cancer.

PURPOSE: We performed a phase I/II dose-escalation trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (CNF) in combination with human recombinant granulocyte-colony-stimulating factor (G-CSF, filgrastim) in patients with advanced breast cancer. The objectives of this trial were (1) to gain experience with filgrastim given to patients with advanced breast cancer and receiving standard-dose CNF, and (2) to determine the maximum tolerated dose of CNF that could be given with filgrastim support by incremental dose escalation of two components of the CNF regimen, cyclophosphamide and mitoxantrone. METHODS: Four patients who had received prior therapy for advanced disease received standard-dose CNF with filgrastim support. Sequentially enrolled patients who had received no prior chemotherapy for advanced disease were treated with standard-dose CNF without filgrastim (5 patients), standard-dose CNF with filgrastim (15 patients), or were entered into sequential cohorts of 3-6 patients to be treated with increasing doses of CNF with filgrastim support (29 patients). RESULTS: The maximum tolerated doses that could be given with filgrastim support were 1500 mg/ml cyclophosphamide, 20 mg/m2 mitoxantrone, and 500 mg/m2 5-FU. Overall, 7 complete (14%) and 13 partial responses (26%) were observed. Despite the use of filgrastim, repeated cycles of CNF at doses of 2000 mg/m2 cyclophosphamide, 25 mg/m2 mitoxantrone, and 500 mg/m2 5-FU could not be given because of neutropenia and thrombopenia. Among 18 patients with bidimensionally measurable disease there were 3 complete (17%) and 5 partial (28%) responses. The median progression-free survival of all patients was 236 days (34 weeks). CONCLUSION: The use of filgrastim allows CNF to be given at approximately twice the dose intensity of "standard"-dose CNF. Because nonhematopoietic toxicity was not dose-limiting, further dose escalation of this regimen might be possible with more effective hematopoietic support. The response rate and survival of patients treated in this study were within the range expected with standard-dose chemotherapy.

Adult↗

Phase II trial of circadian infusion floxuridine (FUDR) in hormone refractory metastatic prostate cancer.

Circadian administration of chemotherapy has been reported to decrease toxicity and possibly enhance efficacy. Between March 1991 and December 1993, 18 evaluable patients with progressive, hormone-refractory metastatic prostate cancer were treated in this phase II trial of circadian infusion floxuridine (FUDR). The drug was delivered through a central venous catheter using a CADD-Plus computerized pump such that approximately 70% of the drug was administered between 3 and 9 p.m. and the rest (30%) was administered between 9 p.m. and 3 p.m. The dose of FUDR was 0.15 mg/kg/day x 14 days every 4 weeks. A total of 79 complete cycles was administered. Two of 18 evaluable patients (11.1%) had decreases in PSA lasting five and eight months. No objective responses or improvement in bone scans was noted. The major toxicity observed was diarrhea. Although circadian infusion FUDR is feasible and tolerable, it has limited activity in hormone refractory prostate cancer.

Antimetabolites, Antineoplastic↗

Phase 1 trial of subcutaneous IL-6 in patients with refractory cancer: clinical and biologic effects.

The authors evaluated the clinical and biologic effects of human recombinant interleukin-6 (rhIL-6) in patients with refractory cancer. A phase 1 trial using escalating doses of rhIL-6 (1-50 microg x kg(-1) x d(-1), Monday through Friday for 4 weeks) was performed in 30 patients. Toxicity was moderate and the maximum tolerated dose was determined to be 25 microg x kg(-1)x d(-1) based on cardiac and neurocortical toxicity in one patient each and thrombocytosis (platelets > 800,000/microL) in three patients. One patient with non-small-cell lung cancer had a partial response after three cycles of therapy. The biologic effects of rhIL-6 included anemia and dose-related thrombocytosis. Various proinflammatory activities were induced and included dose-related cyclical increases in peripheral blood monocytes and the CD14+/CD45RB+ +/- CD16C+ mononuclear cell populations. These increases were accompanied by increased levels of C-reactive protein, serum neopterin, and type I soluble tumor necrosis factor receptor. In contrast, rhIL-6 did not affect lymphocyte numbers or function (cytotoxicity, cytokine levels, immunoglobulin levels), with the possible exception of IL-2Ralpha mRNA induction in peripheral blood lymphocytes. rhIL-6 has pleiotropic proinflammatory actions in vivo and moderate toxicity when administered as long-term therapy.

Acute-Phase Reaction↗