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Biomedical subjects

J S Macdonald

Publications and source records attributed to J S Macdonald.

At least 19 recordsLinked to original sources

Phase II trial of chlorozotocin and fluorouracil in islet cell carcinoma: a Southwest Oncology Group study.

PURPOSE: A phase II trial that used fluorouracil (5-FU) and chlorozotocin (CTZ) was performed in patients with metastatic islet cell carcinoma to determine the response rate and toxicity. PATIENTS AND METHODS: Patients received four cycles of induction chemotherapy. Good-risk patients received 5-FU 800 mg/m2/d days 1 to 4 as a continuous intravenous (IV) infusion (CIV) and CTZ 175 mg/m2 IV on day 1. Poor-risk patients (previous radiation to > or = 25% bone marrow-bearing areas; serum bilirubin > or = 5 mg/dL; creatinine > 1.0 mg/dL) received 5-FU 600 mg/m2/d and CTZ 75 mg/m2 in a similar manner. In responding or stable patients, reduced doses of 5-FU and CTZ were continued as maintenance therapy (maximum, 18 months). RESULTS: Forty-seven of 51 patients were eligible, and 44 received chemotherapy. Fourteen of 44 patients had partial responses, with 13 of 36 (36%; 95% confidence interval [CI], 21.0% to 54.0%) good-risk patients and one of eight (12%; 95% CI, 0.3 to 52.6%) poor-risk patients responding. Median survival of all patients was 25 months, and the median response duration was 11 months. Side effects were moderate to severe and included myelosuppression and gastrointestinal toxicity. Thirteen patients developed renal toxicity, which was severe or life-threatening in five. This seemed to be related to the administration of cumulative doses of CTZ > or = 1,500 mg. CONCLUSION: These results demonstrate that the combination of 5-FU and CTZ has activity in islet cell carcinoma, but the occurrence of renal toxicity secondary to CTZ may limit the use of this agent.

Adenoma, Islet Cell

Phase-II trial of tamoxifen in advanced breat cancer.

Seventy-eight advanced breast cancer patients, most of whom had had prior treatment, were treated with the synthetic antiestogen tamoxifen. The overall objective response rate was 27% (21/78). An additional 19% (15/78) showed disease stabilization. Sixty-seven percent (14/21) of the responses were in soft tissue sites, 24% (5/21) on bony sites and one each occurred in liver and nodular lung disease. Forty percent of patients with soft-tissue disease alone responded, while less than 10% of patients with visceral disease showed responses in visceral sites. The response rate was 28% among patients with a known positive estrogen receptor (ER) assay. It was 21% among patients who had previously received cytotoxic drugs. Toxicity was mild and was seen in nausea and vomiting, hot flushes and vaginal bleeding, and occasional myelosuppression. One patient was withdrawn from the study because of a rash. In two patients the disease flared, once with concomitant hypercalcemia. Tamoxifen is a useful agent for advanced breast cancer even in some patients with visceral disease.

Adenocarcinoma

The role of computed tomography in the management of testicular teratoma.

CT scans of the lungs, mediastinum and abdomen have been performed in 65 patients with malignant teratoma between August 1977 and June 1978. CT is superior to conventional radiology in detecting pulmonary metastases and mediastinal lymphadenopathy. It is a valuable technique for defining the full extent of para-aortic nodal disease and provides more information than lymphography alone. In this series sequential CT scans have been used to monitor treatment response to detect relapse and to assess operability of demonstrable residual disease.

Abdominal Neoplasms

Computed tomography applied to radiotherapy treatment planning: techniques and results.

In order to assess the role of computed tomography (CT) in radiotherapy treatment planning, tumors were localized by conventional techniques and with CT using an EMI CT5005 scanner. CT scans were obtained under conditions simulating radiotherapy. A comparison between the two localizations was made, and detailed results are given. Forty-seven of 123 patients had their treatment plan altered, implying that, provided information is obtained and used correctly, CT can play a significant role in radiotherapy treatment planning.

Abdominal Neoplasms

Studies on mechanisms of 5-fluorouracil resistance in murine and human tumors.

An in vitro cell free assay system to measure phosphorylated products of 5-Fluorouracil is described. Total phosphorylated products and mono-, di and triphosphates of 5-Fluorouracil are measured along with the rate of fluorodeoxyuridylate generation. This assay has been applied to ten murine tumors and eight biopsy specimens from human breast adenocarcinomas. Phosphorylation patterns have been examined in murine tumors demonstrating in vivo sensitivity or resistance to 5-Fluorouracil. There are distinct differences in the patterns of phosphorylation between sensitive and resistant tumors. In a 5-Fluorouracil sensitive murine tumor, mono-, di and triphosphates are produced. In a resistant tumor only monosphophates are produced. Cell free supernatants from human breast tumors produce less total phosphorylation than murine tumors and some specimens produce only monophosphates whereas others produce mono-, di and triphosphates. Human tumors are in general more efficient producers of fluorodeoxyuridylate than murine tumors. These data suggest that resistance to 5-Fluorouracil may correlate with decreased concentration of di and triphosphates of 5-Fluorouracil in some murine tumors. Further experiences is required to demonstrate the value of this easily performed assay system in predicting clinical response to 5-Fluorouracil in man.

Adenocarcinoma

Phase II trial of streptozotocin, mitomycin-C and 5-fluorouracil (SMF) in the treatment of advanced pancreatic cancer.

Ten of 23 patients with advanced measureable adenocarcinoma of the pancreas achieved an objective response after treatment with a regimen consisting of streptozotocin, mitomycin-C and 5-fluorouracil (SMF). The median duration of response is in excess of 7 months and responding patients have lived significantly longer than patients with progressive disease (7.5 + months vs. 3 months). The SMF regimen was adequately tolerated. Principal toxicities included myelosuppression, which was generally mild, nausea and vomiting. There was reversible nephrotoxicity in the form of proteinuria in 30% of patients and persistent axotemia in 9% of patients.

Adult

Tetracycline and quinacrine in the control of malignant pleural effusions. A randomized trial.

Eighteen patients with advanced metastatic malignancy who had 21 pleural effusions requiring sclerosis for control were randomly allocated to intrapleural therapy with tetracycline or quinacrine. Tetracycline produced partial or complete control of the effusion in ten of 12 trials for a median duration of 6 months (range 1.5 to 22 months). Partial or complete control was obtained in nine of ten trials with quinacrine, for a median duration of 3 months (range 1 to 13 months). All complete responders who died achieved control of their effusions until their terminal admissions despite clinical evidence of overt systemic tumor progression in the intervening period. Single-dose tetracycline therapy was accompanied by less fever (p less than 0.04) and less pleuritic pain (p = 0.09) than quinacrine. Tetracycline is effective, well tolerated, easily administered, and should be considered as the initial therapy for malignant pleural effusions requiring pleural sclerosis.

Clinical Trials as Topic

Hepatic estrogen and progesterone receptors in an estrogen-associated hepatic neoplasm.

A patient with a benign hepatic neoplasm developing after treatment with estrogenic hormones is described. After excision, the neoplastic tissue was analyzed for the presence of cytosol estrogen and progesterone binding proteins. The neoplasm was classified as focal nodular hyperplasia of the liver and was demonstrated to contain high-affinity cytosol estrogen and progesterone hormone receptors. The estrogen-binding affinity of the neoplasm was three times greater than that of normal liver. Further investigation of cytosol hormone receptors in estrogen associated hepatic neoplasms will be required to define the role of these binding proteins in the possible etiology of certain liver tumors.

Clinical Trials as Topic

Probable clonal origin of acute myeloblastic leukemia following radiation and chemotherapy of colon cancer.

A 64-yr-old female developed acute myeloblastic leukemia following radiation and drug therapy for colon carcinoma. The patient was heterozygous for glucose-6-phosphate dehydrogenase (G-6-PD) and displayed types A and B isoenzymes in nonhematopoietic tissue. In contrast, only type B G-6-PD was observed in peripheral blood white cells. In addition, a karyotypic abnormality was found in peripheral blood and marrow cells but not in skin fibroblasts. The data are consistent with a clonal origin of this leukemia.

Chromosomes

Phase II trial of 5-fluorouracil, adriamycin, and mitomycin C in advanced colorectal cancer.

Thirty-five patients with advanced measurable colorectal cancer were treated with a combination of 5-fluorouracil (5-FU), adriamycin, and mitomycin C (FAM). Objective regression of tumor was observed in six patients (17%); seven patients (20%) demonstrated stabilization of disease. The FAM regimen was generally well tolerated with toxic effects limited to bone marrow depression and mild-to-moderate nausea and vomiting. FAM combination chemotherapy did not significantly improve survival in responding patients, nor was it more effective than 5-FU alone in achieving objective regression of disease.

Adenocarcinoma

Spontaneous streptococcus pneumonia peritonitis in a patient with metastatic gastric cancer: a case report and etiologic consideration.

Spontaneous peritonitis in adults has not been previously reported to occur in association with ascites of neoplastic origin. We report a patient with metastatic gastric adenocarcinoma in whom spontaneous streptococcus pneumonia peritonitis occurred as a terminal event. Massive metastases may have resulted in significant loss of the hepatic reticuloendothelial system and impaired the capability of the liver to function as an effective bacterial filter, predisposing the patient to bacterial peritonitis.

Adenocarcinoma