Search PubMed⌕ Search

Biomedical subjects

P G de Takats

Publications and source records attributed to P G de Takats.

16 recordsLinked to original sources
PubMed1999

Heterogeneity of chemosensitivity of metastatic cutaneous melanoma.

Advanced melanoma has a poor prognosis and chemotherapy provides little benefit for most patients. This may be related to heterogeneity of chemosensitivity as well as frequent constitutive resistance to individual cytotoxic drugs. We have therefore examined the heterogeneity of chemosensitivity in metastatic cutaneous melanoma specimens using an ex vivo ATP-based chemosensitivity assay (ATP-TCA). Melanoma deposits (n=55) in skin or lymph node were tested using the ATP-TCA, performed in three separate laboratories. Analysis of the data collected (based on an arbitrary sensitivity index < 300) shows considerable heterogeneity of chemosensitivity. The most active single cytotoxic agents in the assay were identified as cisplatin, treosulfan, paclitaxel, vinblastine, gemcitabine and mitoxantrone. There was also a limited direct inhibition of melanoma cell growth by interferon-alpha2b, although this agent is known to have a number of indirect biological antitumor effects. Exposure of tumor cells to combinations of drugs at the concentrations tested as single agents showed the most active combinations to be treosulfan+gemcitabine, cisplatin+paclitaxel and vinblastine+paclitaxel. There was considerable heterogeneity of chemosensitivity: some tumors responded well to one agent or combination, while others showed no response to this and instead responded to one of the alternatives tested. Occasional highly resistant tumors showed no response to any of the single agents or combinations tested. The degree of heterogeneity observed suggests that the ATP-TCA could be used to select patients who might benefit from specific chemotherapeutic agents alone or in combination. This provides the rationale for future randomized controlled trials of ATP-TCA-directed chemotherapy versus physician's choice to determine whether assay-directed chemotherapy can improve patient response and survival.

Adenosine Triphosphate↗
PubMed1999

Pharmacokinetic study of single doses of oral fludarabine phosphate in patients with "low-grade" non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia.

PURPOSE: Fludarabine phosphate (F-AMP), a purine analog, requires daily intravenous administration. A pharmacokinetic study of an oral formulation (10 mg immediate-release tablet) was undertaken in patients with "low-grade" non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia. PATIENTS AND METHODS: Oral F-AMP was incorporated into the "conventional" treatment schedule. Single oral trial doses of 50, 70, and 90 mg of F-AMP were given on the first day of three cycles of treatment; a comparative 50-mg intravenous trial dose was given on the first day of the fourth cycle. Intravenous F-AMP (25 mg/m2) was given on days 2 to 5 at 4-week intervals. Pharmacokinetic samples taken after each trial dose were analyzed for plasma 2-fluoro-arabinofuranosyladenine (2F-ara-A) concentration (its main metabolite); area under the curve 0 to 24 hours (AUC(0-24h)) and maximum concentration (Cmax) were calculated. Eighteen patients received all three oral trial doses, and bioavailability was determined in 15 patients who completed four courses of therapy. RESULTS: Oral administration of F-AMP resulted in a dose-dependent increase in Cmax and AUC(0-24h) of 2F-ara-A and achieved an AUC(0-24h) similar to intravenous administration, although at a lower Cm. The linear increase in mean AUC(0-24h) by factors of 1.36 +/- 0.22 (mean +/- SD) and 1.72 +/- 0.31 corresponded well with the increase in oral dose from 50 to 70 mg (factor of 1.4) and 90 mg (factor of 1.8), respectively. Bioavailability (approximately 55%, with low intraindividual variation) and time to Cmax were dose independent. CONCLUSION: Oral doses of F-AMP can achieve an AUC(0-24h) of 2F-ara-A similar to intravenous administration, with dose-independent bioavailability. The tablet will greatly enhance the use of F-AMP in a palliative setting.

Administration, Oral↗
PubMed1999

Therapeutic trends in cutaneous melanoma.

Many advances in the management of melanoma have occurred in the last few years. These make this an exciting time for clinicians and allows them to offer glimmers of hope for patients with this disease. This article looks at the therapeutic aspects of the treatment of cutaneous melanoma.

Humans↗
PubMed1997

Spontaneous pneumothorax associated with expectoration of a lump of metastatic renal cancer.

The case report of a patient known to have metastatic renal cancer and right main bronchus obstruction is presented. During an episode of haemoptysis, the patient expectorated a large fragment of tissue, which proved to be metastatic renal cell cancer. This event produced a right-sided hydropneumothorax with partial re-expansion of the previously collapsed right lung. A chest tube was inserted producing a full re-expansion, following which pleurodesis with tetracycline was performed. To our knowledge, this is the first ever description of spontaneous clearance of a malignant bronchial obstruction.

Bronchial Diseases↗
PubMed1996

Alpha-foetoprotein heterogeneity: what is its value in managing patients with germ cell tumours?

Alpha-foetoprotein (AFP) is widely used in the diagnosis, therapeutic monitoring and follow-up of patients with germ cell tumours. On occasion, the interpretation of a raised serum AFP measurement in a patient is confounded by the fact that AFP also increases in a variety of liver and gastrointestinal diseases. AFP exists as a number of isoforms, which can be separated by their differential binding to plant lectins. Thus, AFP-concanavalin A (ConA) binding affords a means of distinguishing between a raised AFP of teratoma or liver aetiology and has recently been reported to possess sensitivity and specificity approaching 100%. We present a patient in whom column chromatographic ConA binding was used as a basis for clinical management decisions for treatment for relapsed germ cell testicular tumour. The presumption of high test specificity led to a delay in the diagnosis of cancer recurrence, from which the patient ultimately died. We conclude that the clinical utility of lectin binding assays currently remains uncertain and further evaluation is warranted.

Adult↗
PubMed1996

Is intra-arterial chemotherapy worthwhile in the treatment of patients with unresectable hepatic colorectal cancer metastases?

Regional chemotherapy, from a theoretical and pharmacological stand point, would seem to offer significant advantage over systemic therapy for the treatment of hepatic metastatic colorectal cancer patients. Clinical experience has shown us that the technique itself is fraught with practical problems, but over the years, specialist centres have learned to overcome many of these, making the technique safer and minimising the possibility of complications and toxicity. As a consequence, there is no doubt that high response rates can be achieved with HAI fluoropyrimidines. However, randomised data have only been obtained from small numbers of patients in suboptimally designed trials and, to date, true patient benefit in terms of either survival or quality of life has not been adequately demonstrated. In parallel with the U.S. Intergroup study, the U.K.-based MRC phase III clinical trial of regional versus systemic 5-FU/FA warrants urgent support and we would welcome collaboration with interested European and American centres. The outcome of this trial will fully define the role of HAI chemotherapy in the management of unresectable hepatic metastatic colorectal cancer, in the context of modern, modulated 5-FU.

Antineoplastic Agents↗
PubMed1995

Determination of quercetin in human plasma using reversed-phase high-performance liquid chromatography.

A method is reported for the measurement of quercetin in human plasma using reversed-phase high-performance liquid chromatography (HPLC). Quercetin and kaempferol (as internal standard) were spiked into plasma samples and extracted using C18 Sep-Pak Light cartridges (efficiency > 85%). Flavonoids were eluted with aqueous acetone (50% v/v, pH 3.5), dried down and redissolved in aqueous acetone (45% v/v, pH 3.5). The increased osmolarity promoted a phase separation and the water-saturated acetone layer, containing the flavonoids, was analysed by HPLC with aqueous acetone mobile phase (45% v/v acetone in 250 mM sodium dihydrogen sulphate. The mixture was adjusted to pH 3.5 with phosphoric acid and used at a flow-rate of 1.0 ml/min) and mu Bondapak C18 column (150 x 3.9 mm I.D., 10 microns particle size). The detection limit (A375 nm) for quercetin in plasma was 0.1 microgram/ml (300 nM). The method also detects metabolites of quercetin, although these are not yet identified.

Chromatography, High Pressure Liquid↗
PubMed1995

Abortion.

Explore the source record for details and available documents.

Abortion, Induced↗
PubMed1995

Symptomatic cardiomyopathy as a presentation in Whipple's disease.

A patient presenting with congestive cardiac failure and anaemia underwent investigation which led to the diagnosis of Whipple's disease, associated with dilated cardiomyopathy. Conventional antibiotic therapy for Whipple's disease resulted in resolution of the traditional features of Whipple's disease and a marked improvement in the patient's heart failure.

Aged↗
PubMed1994

Hepatic arterial chemotherapy for metastatic colorectal carcinoma.

In this review, the rationale of regional chemotherapy for treatment of hepatic metastases in advanced colorectal carcinoma is discussed. Pharmacokinetic principles and early clinical experience of hepatic arterial drug administration are summarised. The regional advantage of fluoropyrimidine compounds in this setting is well established, and recent evidence suggests that 5-fluorouracil (5-FU) is more efficacious than the analogue 5-fluoro-2'-deoxyuridine (FUDR). However, while significantly higher clinical response rates can be achieved with hepatic arterial infusion (HAI) chemotherapy compared with conventional intravenous drug administration, patient survival benefit is not significantly different. Several novel approaches to overcome the limitations of HAI therapy are currently being explored. These include concomitant use of biodegradable microspheres, which both slow tumour blood flow and enhance tumour drug uptake, and use of vasoactive agents to redistribute arterial blood flow towards tumours. In addition, novel chemotherapeutic agents which exploit unique biological characteristics of hepatic tumours are entering clinical trial.

Colorectal Neoplasms↗
PubMed1993

Impact of adjuvant chemotherapy in breast cancer on response to tamoxifen at relapse.

A series of 105 patients with operable breast cancer previously entered in the WMOA adjuvant therapy trials were reviewed in order to assess methods of treatment on relapse and subsequent patterns of relapse and survival, related to previous adjuvant therapy. Tamoxifen was the predominant medical therapy offered on relapse. Unexpectedly, analysis of the relapse and survival data for these hormone-treated patients suggested that prior adjuvant therapy negatively influenced response to tamoxifen, with overall survival of treated and control patients being identical. Although not statistically significant, possible explanations of this trend have been explored.

Antineoplastic Combined Chemotherapy Protocols↗