Biomedical subjects
Publications and source records attributed to D A Decker.
Fluorouracil alone can cause a variety of dermatologic adverse effects; however, it is not considered to be a chemical vesicant. We report a case of apparent enhanced local skin reaction from the combination of intravenous fluorouracil and leucovorin. The reaction occurred in the patient's other hand on rechallenge.
A new method (Freeze-Transfer) is described for performing high-resolution immunocytochemistry for soluble cell proteins on frozen sections of biological tissues that involves thaw-mounting frozen tissue sections directly onto the surface of nitrocellulose thin films instead of directly onto glass slides. This technically straight-forward change in methodology resulted in chromogenic immunocytochemical assays for Her-2 and EGF receptors that were 1-2 orders of magnitude more sensitive while still fully utilizing the diagnostic resolving power of light microscopy. The effects of membrane pore size and surface chemistry on the resolution and intensity of Her-2 signal suggest that the enhanced sensitivity of Freeze-Transfer was caused by the cytologically coherent transfer of target molecules normally lost from cut surfaces of cells mounted on nonporous glass during assay.
Sixteen women with advanced epithelial ovarian carcinoma were treated with Aclacinomycin-A 40 mg/M2 given as a weekly infusion for four consecutive weeks followed by a two week rest period. All had failed prior chemotherapy. No responses were observed. Nausea and vomiting were the most frequent side effect. Myelosuppression was minimal. This dose and schedule of Aclacinomycin-A are not recommended for further trials in ovarian carcinoma.
Nineteen patients with biopsy-proven high-grade astrocytomas received as initial treatment whole-brain radiation and combination chemotherapy with 5-fluorouracil (5-FU), 1,000 mg/m2/24 h as a continuous infusion for 96 h, and bolus cisdiamminedichloroplatinum II (CDDP), 100 mg/m2. Chemotherapy cycles were repeated on day 21, then every 28 days until progression or completion of six cycles. All 19 patients completed one cycle of chemotherapy. Toxicity was moderate, with cytopenias, nausea, vomiting, diarrhea, stomatitis, and reversible azotemia. Survival ranged from 2 to 160+ weeks, with a median of 35 weeks. The survival of the pilot group was compared with historical controls treated with radiation plus 1,3,-bis(2-chloroethyl)-1-nitrosourea (BCNU). Controls were similar in histology, age, performance score, and survival, without statistically significant differences. The combination of radiation therapy, continuous-infusion 5-FU, and bolus CDDP as described here for high-grade astrocytomas is moderately toxic and appears to offer no survival advantage compared with radiation therapy plus BCNU.
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Twenty-two patients with advanced measurable renal cell carcinoma were treated with AZQ 20 mg/m2 weekly for 4 weeks, followed by a 2-week rest. No complete or partial responses were observed among 15 fully evaluable patients. Stabilization was observed in eight individuals (range 8-27 weeks with a median of 12.5 weeks). Toxicity was primarily reversible myelosuppression. We conclude that AZQ administered at this dose and schedule has no significant activity against advanced renal cell carcinoma.
High-dose ketoconazole, 400 mg orally every 8 h, was administered in two groups of patients with metastatic prostate cancer. Group A consisted of 10 patients who had not undergone orchiectomy and Group B, eight patients who had orchiectomy prior to the study. Significant declines in testosterone, androstenedione, and dehydroepiandrosterone levels, reciprocal elevation of the gonadotropin levels (FSH and LH), and a persistent fall in serum acid phosphatase levels were observed in Group A patients. Three Group A patients achieved a partial objective remission (duration 9, 41+, and 69 weeks); four patients, stabilization of their disease for a median of 33.5 weeks (range 16-40+ weeks); and two progressed (The National Prostatic Cancer Project Criteria). Stable disease in two Group B patients (7 and 20 weeks) and progression in four patients were observed. Gastrointestinal irritation was the main toxicity and was similar in both groups. Two Group A patients developed symptomatology consistent with adrenal insufficiency. Ketoconazole can suppress androgen production and has a beneficial role in the hormonal therapy of patients with prostate cancer who have not undergone orchiectomy.
Seventeen patients with malignant gliomas recurrent after chemotherapy and/or radiation failure were treated with aziridinylbenzoquinone (AZQ) at a dose of 20-15 mg/M2 weekly for four weeks followed by a two week rest. Regression of disease was observed in four patients, 4/17 (24%) for 35, 15+, 40+, and 10 weeks. Toxicity was limited to moderate reversible myelosuppression. AZQ in this dose and schedule has limited but definite activity in patients with malignant gliomas progressive after primary radiation therapy failure.
Four hundred thirty-eight patients with metastatic breast cancer treated with nine prospective randomized trials were reviewed to analyze, characterize, and compare those with complete regression (CR) (N=49 [11%]) with those with noncomplete regression (non-CR) (N=389 [89%]). Site of dominant disease was identical in the CR and non-CR patients. However, CR was statistically more likely when the disease-free interval and the postmenopausal status was five years or less. Survival and time to progression occurred at sites of prior dominant disease, except that relapses occurred in the CNS in 14%. Six CR patients received prolonged chemotherapy and were believed to be "cured" when treatment was discontinued; however, all except one have had relapses.
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Bronchogenic carcinoma complicated by ipsilateral cytologically positive effusion is considered unresectable. Bronchogenic carcinoma with cytologically negative effusion, even if bloody, has also been thought by many to be unresectable. Seventy-three patients with bronchogenic carcinoma and ipsilateral cytologically negative effusions were studied. Sixty-six underwent exploratory thoracotomy for staging or therapy; five had pleural biopsies and two had mediastinoscopies, all disclosing metastatic carcinoma. Four of the 73 patients (5.5 percent) had surgically resectable disease. They have remained free of disease for 3, 6, 7, and 14 years. Sixty-nine patients (94.5 percent) had unresectable carcinoma with metastases. Seventeen (94 percent) of 18 patients with bloody effusions had unresectable cancer. Carcinoma was resected in one patient with cytologically negative bloody effusion, and the patient remained free of disease during the 14-year follow-up period. Unresectability must be documented surgically in these patients to exclude those in whom curative resection can be performed.
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