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Biomedical subjects

D Cunningham

Publications and source records attributed to D Cunningham.

At least 55 records · Page 3Linked to original sources
PubMed1993

A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy.

Twenty-six patients, whose B-cell lymphoma had relapsed after conventional therapies, were treated in a phase I dose escalation study with an immunotoxin consisting of a mouse CD22 monoclonal antibody (RFB4:IgG1K) coupled to chemically deglycosylated ricin A chain (dgA). Two to 12 doses of the immunotoxin were infused intravenously at 48-hour intervals. The peak serum concentration and half-life (T1/2) did not correlate directly with the dose and averaged 3.8 micrograms/mL and 7.8 hours, respectively. The main dose-limiting toxicity was caused by the vascular leak syndrome (VLS) consisting of weight gain, edema, serum albumin decrease, and critically by pulmonary edema. Myalgia occurred frequently and was only dose limiting in one patient who developed rhabdomyolysis. The presence of lymphoma cells in the blood (> or = 10(10)/L) and clinically detectable splenomegaly were associated with reduced toxicity and a shorter T1/2. Nine of 24 evaluable patients (37.5%) made antibody to either mouse Ig or dgA. There were five partial responses (PR) and one complete response (CR) lasting 30 to 78 days. High peak concentrations of immunotoxin in the serum, a long T1/2, and large areas under the curve (AUC) correlated with both clinical response and toxicity. None of three patients with CD5+ lymphomas (including two CLL patients) had more than mild toxicity or responded to the immunotoxin.

Adult↗
PubMed1993

Meningeal carcinomatosis from transitional cell carcinoma of the bladder.

Response rates of over 50% can be achieved in patients with metastatic transitional cell carcinoma of the bladder treated with cisplatin-based chemotherapy. With prolonged survival, intraparenchymal brain metastases may occur in as many as 12% of patients who received methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy. Meningeal carcinomatosis from urothelial cancer is rare, however. A 71-year-old man, with metastatic, transitional cell carcinoma of the bladder, attained an excellent partial response to M-VAC chemotherapy. He subsequently presented with an acute confusional state 6 months after diagnosis. Head computed tomographic studies were nondiagnostic. Gadolinium-enhanced magnetic resonance images (MRI), however, demonstrated multifocal 1-cm nodules in the brain parenchyma and enhancement of the meninges. Meningeal carcinomatosis was confirmed by lumbar puncture. Records of 40 patients with advanced transitional cell carcinoma of the bladder treated with chemotherapy between 1977 and 1992 at a cancer center were reviewed retrospectively for the occurrence of documented meningeal carcinomatosis, intraparenchymal brain metastases, or both. Among 13 responders, only 1 other patient, a 64-year-old man, was identified who had minimal metastatic disease and attained a complete response to methotrexate and cisplatin. The patient relapsed 2 years after response, with cerebellar metastases and meningeal carcinomatosis. Central nervous system (CNS) metastases in patients with transitional cell carcinoma of the bladder are unusual. Although parenchymal brain metastases may be more common after prolonged remissions induced by combination chemotherapy, meningeal carcinomatosis remains uncommon. MRI may be a useful adjunct in the diagnosis of CNS metastases. A high index of clinical suspicion for the occurrence of CNS metastases from transitional cell carcinoma is encouraged.

Aged↗
PubMed1993

The real costs of emesis--an economic analysis of ondansetron vs. metoclopramide in controlling emesis in patients receiving chemotherapy for cancer.

The cost effectiveness of ondansetron was compared with that of metoclopramide in the prevention of acute emesis due to highly emetogenic chemotherapy in an open, randomised, parallel group pilot study. Ondansetron was given as three 8 mg intravenous doses (0, 4 and 8 h) and metoclopramide as an intravenous loading dose (3 mg/kg) followed by a maintenance dose of 0.5 mg/kg/h for 8 h. Therapeutic outcomes and full utilisation costs, that is nursing time, material costs, in addition to drug acquisition prices were recorded for each antiemetic for 24 h following chemotherapy. The cost per successfully treated patient (< or = 1 emetic episode and no adverse events) was 95.20 pounds for ondansetron and 92.18 pounds for metoclopramide. The results of the study therefore suggest that for the control of acute emesis due to highly emetogenic chemotherapy ondansetron and metoclopramide are equally cost-effective treatments.

Antineoplastic Agents↗
PubMed1993

A pilot study of cisplatin based combination chemotherapy in gastric cancer.

A pilot study evaluating cisplatin in combination with 5-fluorouracil, methotrexate and epirubicin in advanced gastric cancer was initiated. Twenty patients were treated, eight with locally advanced or recurrent disease, and 12 with metastatic gastric cancer. The overall response rate was 35% (95% confidence interval 14%-56%).

Adult↗
PubMed1993

2'-Chlorodeoxyadenosine: evaluation of a novel predominantly lymphocyte selective agent in lymphoid malignancies.

2'-Chlorodeoxyadenosine (2CDA) is a purine analogue selectively active against both resting and dividing lymphoid cells. Twenty-one patients with a variety of previously treated lymphoid malignancies received a total of 41 courses of 2CDA (0.1-0.15 mg/kg/day over 7 days continuous intravenous infusion) on compassionate grounds. The profile of the patient population was as follows: low grade non-Hodgkin's lymphoma (NHL) = 8, intermediate grade NHL = 2, transformed (intermediate grade NHL) = 6, Hodgkin's disease = 1, lymphoplasmacytoid NHL = 3 and lymphoblastic NHL = 1. The overall response rate was 53%, with three patients attaining complete remission (CR) and eight partial remission (PR). Three of 16 patients with primary resistant or resistant recurrent disease entered either CR (1) or PR (2). Ten patients had no response or progressive disease. The latter group was comprised of patients who had extensively pre-treated lymphoplasmacytoid tumours and/or poor performance status (WHO grades 2-4). The median duration of response is 6 months (range 1 to 12 months). Treatment was well tolerated and the chief toxicities were leucopenia and thrombocytopenia which were most pronounced when there was bone marrow involvement. As a result of dose limiting myelotoxicity, a dose escalation to 0.15 mg/kg/day was possible on just three occasions. These data confirm other reports of the activity of 2CDA in low grade NHL and indicate it may have activity in Hodgkin's disease. There was no demonstrable activity in poor performance status patients or those with extensively pre-treated lymphoplasmacytoid tumours.

Adult↗
PubMed1993

EPIC: an effective low toxicity regimen for relapsing lymphoma.

We have treated 40 patients was relapsed or resistant lymphoma with the combination of Etoposide, Prednisolone, Ifosfamide and Cisplatin (EPIC). Complete response was obtained in 11 patients (28%) with an overall response of 58%. The presence of bulky disease (P < 0.005), elevated LDH serum levels (P < 0.005), response to prior chemotherapy (P < 0.01) and B symptoms (P < 0.005) were significantly associated with response. However on multivariate analysis only the presence of bulky disease and of B symptoms were independent adverse factors for response and for survival. The regimen was well tolerated with myelosuppression being the most common toxicity. Leucopenia < or 1,000 microliters-1 and thrombocytopenia < or = 25,000 microliters-1 developed in 27% and 4% of cycles respectively. There were no treatment related deaths. The EPIC regimen has equivalent activity to other reported cisplatin based regimens used in the treatment of recurrent lymphoma, but is associated with lower treatment related morbidity and mortality.

Adult↗
PubMed1993

The effect of 1,25-dihydroxyvitamin D3 on lymphoma cell lines and expression of vitamin D receptor in lymphoma.

1,25(OH)2D3 promotes differentiation and has an antiproliferative effect in a variety of cell lines derived from the immunohaematopoetic system. alpha-Calcidol which is metabolised to 1,25(OH)2D3 has been shown to produce tumour regression in follicular low grade non-Hodgkin's lymphoma (NHL) and the dose limiting toxicity is hypercalcaemia. The cellular action of 1,25(OH)2D3 is mediated by binding to an intracellular protein, the vitamin D receptor (VDR). We have evaluated the activity of 1,25(OH)2D3 and its non-calcaemogenic analogue MC903 in the SU-DHL4 and SU-DUL5 B cell lines which carry the 14;18 translocation characteristic of follicular NHL, and also the expression of the VDR in a range of B cell NHLs. Both agents induced differentiation and had an antiproliferative effect on the SU-DHL4 and SU-DUL5 cell lines. However this occurred at a relatively high concentration (10(-7) M) which exceeds the physiological concentration of 1,25(OH)2D3 by approximately 10(3)-10(4)-fold. Expression of the VDR was low in each cell line and in the low grade lymphoma tumour samples. To account for the observed clinical response to 1 alpha OHD3 (alpha-calcidol) in follicular NHL a network is suggested whereby 1,25(OH)2D3 modulates the activity of CD4+T cells which have previously been shown to promote follicle centre cell proliferation. Vitamin D3 analogues may enable serum levels to be achieved which produce a direct action on follicular lymphoma cells without disturbing calcium metabolism.

Biopsy↗
PubMed1993

Repeat administration of high dose melphalan in relapsed myeloma.

At a median time of 20 months following high dose melphalan for myeloma, 29 patients relapsed and were treated with induction chemotherapy to maximum response followed by a second course of high dose melphalan. The majority (90%) of patients received 200 mg m-2 with an autologous bone marrow transplant. Sixteen (55%) patients achieved complete remission and 11 (38%) a partial response. The median duration of remission was 17 (4-42) months. The median survival has not been reached, with 50% of patients alive at 58+ months after presentation. The period of neutropenia was similar during both first and second high dose procedures, but the duration of thrombocytopenia was longer in patients receiving melphalan for a second time (median 22 (16-56) days and 41 (18-69) days respectively). There was one treatment-related death due to thrombocytopenic haemorrhage. Repeated administration of high dose melphalan is a feasible approach for patients with relapsed myeloma.

Adult↗
PubMed1993

The non-invasive monitoring of low dose, infusional 5-fluorouracil and its modulation by interferon-alpha using in vivo 19F magnetic resonance spectroscopy in patients with colorectal cancer: a pilot study.

BACKGROUND: 5-Fluorouracil (5-FU) is the most widely used cytotoxic drug in oncology and the only one useful in the management of colorectal cancer - a leading cause of cancer death worldwide. Recent studies of 5-FU have focused on increasing efficacy and reducing toxicity by varying the delivery schedule and combining it with modulators. With the development of whole body magnetic resonance systems it is now possible to examine the metabolism of 5-FU in vivo by exploiting the magnetic properties of the fluorine atom which is an integral component of the drug. PATIENTS AND METHODS: Magnetic Resonance Spectroscopy (MRS) was used to non-invasively monitor the metabolism of 5-FU in the liver metastases of colorectal cancer patients. The patients were treated with a continuous low dose intravenous infusion of 5-FU until the point of refractory disease, at which time interferon-alpha was added with the objective of modulating 5-FU activity. MRS was performed at specific phases of the treatment. RESULTS: Twenty-six patients were treated with 5-FU, 11 (42%) achieving partial response. Of the 15 given interferon when disease became refractory to 5-FU, 4 showed signs of further response. In patients observed by MRS during the first 8 weeks of 5-FU treatment, those with a visible 5-FU signal were likely to respond to treatment (p = 0.017). At the time of interferon-alpha addition, MRS showed that 7 patients developed new or increased 5-FU signals, and 4 patients showed a signal from the active metabolites of 5-FU. The patients who exhibited a new or increased 5-FU signal were more likely to show further response to interferon-alpha (p = 0.007). CONCLUSIONS: MRS is a powerful technique for monitoring intratumoural metabolism and modulation of 5-FU enabling prediction of tumour outcome. Direct metabolic information may facilitate the rapid development of optimal clinical schedules for 5-FU and its modulators, thus maximising antitumour effect and minimising toxicity to the patient. This technique may be applied to other areas of clinical medicine where knowledge of the tissue metabolism of a fluorinated drug is of interest.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Long-term follow up of patients treated with a software based antitachycardia pacemaker.

INTRODUCTION: Over the past decade, several advances have been made in the management of tachycardias by pacing techniques, but limited data are available on the long-term outcome of patients treated with antitachycardia pacemakers. PATIENTS AND METHODS: An antitachycardia pacemaker, the Intermedics Intertach, was implanted in 22 (17 female) patients with supraventricular tachycardia over a five year period. All were selected after detailed evaluation and testing of a temporary antitachycardia pacemaker system showed that their arrhythmia could be stopped promptly, reliably, and under different physiological conditions. RESULTS: The 22 patients have been followed up for a mean period of 57.3 (range 19-76) months. All except one of the patients has had frequent episodes of tachycardia reliably ended by the pacemaker. Complications have occurred in seven patients, necessitating removal of the pacing system in four. Of the 18 patients who continue to have pacemakers, seven are being treated with beta blockers or verapamil; no other antiarrhythmic drugs are being taken. CONCLUSIONS: Antitachycardia pacing is an acceptable long-term option for carefully selected patients with supraventricular tachycardia, but even after extensive testing a substantial number of the patients may continue to require drug treatment. Furthermore, the widespread use of curative techniques for supraventricular arrhythmias (catheter ablation and surgery) has decreased the need for this palliative treatment.

Adolescent↗
PubMed1993

Prognostic significance of transient ST segment changes after coronary artery bypass surgery: a long-term (4-10 year) follow up study.

OBJECTIVE: To assess the long-term (four to 10 years) prognostic significance of transient ST segment changes on ambulatory ST segment monitoring after coronary artery bypass grafting (CABG). PATIENTS AND METHODS: 76 patients (67 men, nine women) underwent CABG between 1982 and 1984 (n = 31) and between 1987 and 1988 (n = 45) and at a mean age of 57. All underwent 48 hours of ambulatory ST segment monitoring at a mean of 19 weeks after surgery. The results were available for assessment. All general practitioners were contacted and patients' notes reviewed. Patients were contacted by telephone. Details were recorded of intervening events (acute myocardial infarction, unstable angina, need for further revascularisation, and deaths). Event free survival curves were produced for those with and without transient ST segment changes during routine postoperative ambulatory ST segment monitoring. RESULTS: During 3213 hours of monitoring after CABG, 21 (27.6%) of 76 patients had transient ST segment changes, of which 70% were silent. Over a mean 70 month follow up period, patients with such ischaemic changes were no more likely to have either an objective (myocardial infarction or cardiac death) or subjective (unstable angina or another revascularisation) event than those patients without ischaemic changes. This finding was the same in patients operated on between 1987 and 1988 and between 1982 and 1984. CONCLUSIONS: Although ambulatory ST segment monitoring is becoming increasingly popular in some countries as a routine investigation for ischaemia in various coronary subgroups, the findings of such an investigation, when performed after CABG, do not help to identify a subgroup more likely to have an adverse outcome during up to 10 years of follow up. There seems to be no reason to perform this investigation after surgery, and particularly to refer patients for reinvestigation because of the detection of predominantly silent ST segment changes of uncertain relevance.

Adult↗