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Biomedical subjects

S B Kaye

Publications and source records attributed to S B Kaye.

At least 271 records · Page 15Linked to original sources
PubMed1989

The impact of chemotherapy in germ cell tumours.

It is widely appreciated that the application of chemotherapy in the treatment of germ cell tumours exemplifies the best results to be expected from this approach in solid tumours, since the majority of patients treated are now cured. Against a background of steadily rising incidence of testicular cancer, the impact of this highly effective treatment can be measured using national statistics, which for most countries in the developed world indicate a corresponding fall in mortality over the past 15 years. For some countries, however, no such improvement has taken place, presumably reflecting inadequate facilities in those countries for securing appropriate treatment, particularly cisplatin. In most specialist centres, current clinical studies are aimed at reducing the toxicity of treatment for the majority of patients cured of their disease. The other remaining challenge in management is to improve the results of treatment in the small minority of patients for whom chemotherapy is still not curative. More intensive schedules are being tested, and randomized trials to test these approaches are recommended.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Comparative cellular uptake and cytotoxicity of a complex of daunomycin-low density lipoprotein in human squamous lung tumour cell monolayers.

In an attempt to target cytotoxic drugs to tumour cells daunomycin-low density lipoprotein (LDL) complexes were synthesised. Human squamous lung tumour cells in vitro have large numbers of high affinity cell surface LDL receptors (Vmax = 19 ng LDL/micrograms cell protein per 24 hr; Km = 23 micrograms/ml). Cellular uptake of daunomycin and LDL-daunomycin was rapid and approached equilibrium by approximately 3 hr. Intracellular daunomycin concentrations were similar at each time point regardless of whether free drug or the complex was used. The degree of intracellular drug metabolism differed markedly with significantly higher production of daunomycinol following exposure to free daunomycin for 90 min. Daunomycin and LDL-daunomycin were equally cytotoxic in vitro (respective clonogenic ID90s of 1 microgram/ml and 0.7 microgram/ml). Fluorescence microscopy indicated that both free daunomycin and LDL-daunomycin have a punctate, granular distribution within the cytoplasm.

Carcinoma, Squamous Cell↗
PubMed1988

Optimisation of a reversed-phase high-performance liquid chromatographic method for the determination of flavone acetic acid and its major human metabolites in plasma and urine.

A high-performance liquid chromatographic method for the determination of flavone acetic acid (FAA) and its major human metabolites in plasma and urine is described. Two factors were identified as being the key to resolving the metabolites; pH and buffer ionic strength. Run at optimal conditions of 10 mM ammonium acetate, pH 5.5-propan-2-ol (80:20) and a column temperature of 40 degrees C on a muBondapak C18 10 microns particle column (30 cm X 3.8 mm I.D.), two major metabolites were identified [FAA, retention time (tR) 6.02 min +/- 0.5% coefficient of variation (C.V.); metabolite 1, tR 4.13 min +/- 1.1% C.V.; metabolite 2, tR 5.10 min +/- 0.5% C.V. and hesperidin, internal standard, tR 4.69 min +/- 1.6% C.V.]. A solid-phase technique using Bond Elut C2 40-microns particles is described which extracts FAA, metabolites and internal standard with efficiencies in excess of 90%. Considerable attention has to be paid to sample preparation: FAA has poor aqueous solubility at acidic pH and the metabolites degrade back to FAA via intermediates at alkaline pH. Both problems can be avoided by buffering and diluting samples with 10 mM ammonium acetate, pH 5.5.

Antineoplastic Agents↗
PubMed1988

Early electroretinography in unilateral central retinal vein occlusion as a predictor of rubeosis iridis.

Twenty-six patients with clinically nonischemic unilateral central retinal vein occlusion and four in whom clinical categorization was unclear were recruited. The scotopic electroretinogram (ERG) was recorded at presentation to a range of six different luminances. Patients were followed up for six months to assess the correlation between initial ERG response and subsequent outcome. Seven patients developed rubeosis iridis. The b-wave implicit time was the parameter most significantly associated with subsequent rubeosis, followed by b-wave/a-wave amplitude ratio and then b-wave amplitude. Neither a-wave amplitude nor implicit time was a valuable predictor. The b-wave implicit times were equally predictive of rubeosis at each of the luminances used. In individually affected eyes, a b-wave implicit time at presentation, averaged across the range of luminances used, of greater than 47.17 ms was strongly associated with later rubeosis, as was an intereye difference of greater than 7.39 ms.

Electroretinography↗
PubMed1988

Hepatocellular and gastric carcinoma associated with familial polyposis coli.

A case of familial polyposis coli in association with hepatocellular and gastric carcinoma is reported. No similar case has ever been documented in the world literature. This may be surprising as it is well known that familial polyposis has a potent oncogenicity not only in the colon but also in extracolonic organs.

Adenomatous Polyposis Coli↗
PubMed1988

Flavone acetic acid: a nonlinear pharmacokinetic model.

Flavone acetic acid pharmacokinetics were studied in 31 patients in a phase I clinical trial. The drug was given by i.v. infusions over 1, 1.5, 3, and 6 h at doses ranging from 0.5 to 6.4 g/m2. The pharmacokinetic parameters were determined according to a nonlinear model including Michaelis-Menten-type kinetics. The mean elimination half-life is 4.8 h and the mean volume of distribution of the central compartment, 7.61. Our model predicted a maximal tolerated dose (MTD) of 11.1 g/m2 on the basis of the "therapeutic window" concept, very close to the clinically observed MTD of 10 g/m2. This model is also operational when different protocols of inoculation are considered, such as a divided-dose schedule vs a unique infusion, and indicates that, at the MTD, injections should be made every 72 h to avoid drug accumulation.

Algorithms↗
PubMed1988

The pharmacokinetics of high dose cyclophosphamide and high dose etoposide.

We have studied the pharmacokinetics of single agent high dose cyclophosphamide (HDC) (160-240 mg kg-1) given as repeated intravenous (i.v.) infusions to six patients with small cell lung cancer (SCLC), and HDC (180 mg kg-1) combined with etoposide (750-1000 mg m-2) as repeated i.v. infusions to five patients with SCLC and two patients with teratoma. HDC has a similar pharmacokinetic profile to low dose cyclophosphamide, with a half-life of 4.83 +/- 1.3 h. Repeated administration of HDC produced a small but significant shortening of the half life (P = 0.02). The terminal half-life of high dose etoposide was 7.7 +/- 2 h which is similar to our previous results with low dose etoposide (50-300 mg m-2), but the volume of distribution which was 35.5 +/- 11.6 1. was significantly increased (P less than 0.001). Plasma steady state concentrations of 26.2 +/- 11.7 micrograms ml-1 were achieved. The possible mechanism for the alteration of volume of distribution of etoposide will be discussed.

Carcinoma, Small Cell↗
PubMed1988

Adriamycin, vincristine and mitomycin C as first and second line therapy for advanced breast carcinoma.

Forty-three patients with advanced breast cancer were treated with adriamycin, vincristine and mitomycin C at 6 week intervals. Adriamycin 40 mg m-2 and vincristine 1 mg m-2 were given on days 1 and 22: patients treated early in the study received 10 mg m-2 mitomycin C, but in view of repeated treatment delays the dose was reduced to 6 mg m-2. Thirty-two women had received prior hormone therapy and 24 previous chemotherapy. Responses were seen in 15 of 38 evaluable patients (40%) with a further 9 (24%) achieving disease stabilization. Median duration of response was 10 months and of disease stabilization was 5 months. Overall median survival for the whole group was 8 months, but 16 months for the 15 responding patients, five of whom survived beyond 2 yr. Responses were seen more frequently in patients who had received no prior chemotherapy. Myelosuppression may have contributed to three of the five early deaths in the non-pretreated group. Other significant side effects were alopecia, gastrointestinal toxicity and malaise.

Adult↗
PubMed1988

Pharmacokinetics of cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV (iproplatinum, CHIP) in patients with normal and impaired renal function and following intraperitoneal administration.

CHIP is a quadrivalent platinum (Pt) complex, introduced clinically as a less toxic alternative to cis-platinum. The drug's major route of excretion is via the kidneys, and in this study the pharmacokinetics of unchanged CHIP, filterable Pt and total Pt have been determined following intravenous administration to patients with a range of renal function. Total Pt and filterable Pt in plasma decayed biexponentially and was fitted to a two-compartment model, whereas unchanged CHIP declined monoexponentially and was best fitted to a one-compartment model, according to Akaike's information criteria. There is a correlation between the unchanged CHIP clearance and 51Cr-EDTA clearance. The pharmacokinetics of CHIP was determined following intraperitoneal (i.p.) administration (dose, 150-300 mg m-2 4 h dwell time) and a regional advantage (peritoneal peak concentration/plasma peak concentration) of approximately 30 fold was seen. It is likely that the dose of CHIP will need to be reduced in patients with impaired renal function, and the use of i.p. CHIP in ovarian carcinoma warrants further study.

Female↗
PubMed1988

A phase II study of sequential methotrexate and 5-fluorouracil in colorectal carcinoma.

Nineteen patients with locally recurrent or metastatic colorectal carcinomas were treated with 3-weekly cycles of methotrexate (MTX) given as a loading dose of 100 mg m-2 and a subsequent 12 h infusion of 400 mg m-2, followed by 5-fluorouracil (5-FU) 900 mg m-2 as a bolus injection on completion of infusion. No objective responses were seen in 14 evaluable patients. One early death was treatment related, and four patients were withdrawn from the study after a single course as toxicity was considered unacceptable. The results suggest that in this regimen of sequential MTX and 5-FU, any synergism may be restricted to drug toxicity as no therapeutic benefit was evident.

Adult↗
PubMed1988

Onco-developmental protein concentrations in the sera of patients with ovarian cancer prior to treatment.

Eight onco-developmental proteins have been measured in the serum of women prior to their operation and treatment for ovarian cancer. Alpha-foetoprotein, CEA, hCG and PAPP-A were not often elevated whereas CPAP, SP1, CanAg 50 and CA 125 were. Many of our findings differed from those of previous workers, possibly due to differences in clinical material and analytical technique. We conclude that large profiles of tumour markers are no longer of use in the investigation of ovarian cancer. At the present time we think that CA 125 could prove the most useful marker in the investigation of ovarian cancer.

Adenocarcinoma↗
PubMed1988

Improving prognosis of Hodgkin's disease in Scotland.

Time trends in mortality from Hodgkin's disease have been studied in Great Britain for the 70-year period, 1911-1980, and incidence in Scotland since 1959. In both Scotland and England and Wales, in each sex, mortality from Hodgkin's disease rose steadily from 1911 until 1970 and thereafter dropped substantially; the greatest fall was apparent in Scottish males. While mortality rates continue to decline in Scotland the incidence has remained fairly constant over the last 25 years suggesting a major change in prognosis for this disease. The introduction of effective chemotherapy and improved techniques of radiotherapy appear to have improved prognosis sufficiently, and to have been made adequately widely available, as to influence overall mortality rates at a national level as well as at the level of the clinical trial. No such improvement in prognosis, however, explains the declines observed in mortality rates among children of each sex in both areas which have taken place since the 1930s. In view of the current knowledge of the aetiology of Hodgkin's disease this fall may have been brought about by changes in socioeconomic factors.

Age Factors↗
PubMed1988

A randomized trial of oral nabilone and prochlorperazine compared to intravenous metoclopramide and dexamethasone in the treatment of nausea and vomiting induced by chemotherapy regimens containing cisplatin or cisplatin analogues.

Eighty patients receiving their first course of chemotherapy with regimens containing cisplatin or cisplatin analogues entered this open crossover study comparing nabilone 2 mg and prochlorperazine 5 mg given orally every 12 h for four doses against metoclopramide 2 mg/kg loading dose intravenously (i.v.), then 3 mg/kg as an (i.v.) infusion over 8 h and dexamethasone 20 mg (i.v.) over 3-5 min at the time of chemotherapy. There was complete control of nausea and vomiting in 24 patients (32%) given metoclopramide and dexamethasone compared to 14 patients (19%) given nabilone and prochlorperazine. For the 70 patients who completed the crossover assessment of emesis on a linear analogue scale significantly favoured metoclopramide and dexamethasone (P = 0.02). However, there was no overall patient preference for the metoclopramide and dexamethasone combination (nabilone and prochlorperazine 31 vs. metoclopramide and dexamethasone 26; 13 no preference), because a significant proportion of the patients receiving the cisplatin analogue carboplatin preferred nabilone and prochlorperazine (16 vs. 5; 1 no preference; P = 0.013). For patients receiving cisplatin chemotherapy metoclopramide and dexamethasone remains the antiemetic of choice but for regimens containing carboplatin, nabilone and prochlorperazine is better tolerated and preferred by the patients.

Adolescent↗
PubMed1988

Phase II study of the antifolate N10-propargyl-5,8-dideazafolic acid (CB 3717) in advanced breast cancer.

Fifty-two patients with progressive advanced breast cancer were treated with the novel antifolate CB 3717 (N10-propargyl-5,8-dideazofolic acid) which inhibits thymidylate synthetase. Forty-six patients were pretreated with hormones, 43 with cytotoxic chemotherapy and 39 patients with both treatments. Eight of 48 patients (16.6%) evaluable for response had partial responses (confidence limits 7.4-30.2%, 95% confidence level) following CB 3717 administration. Liver function abnormalities, reversible in most cases, were the most commonest toxicities and were frequently accompanied by malaise. Severe renal failure occurred in eight patients, five of whom had had partial responses to CB 3717. This study shows the importance of thymidylate synthetase as a target for therapy but the clinical value of CB 3717 is limited by its hepatic and renal toxicities.

Acute Kidney Injury↗
PubMed1988

A negative phase II trial methylene dimethane sulphonate in advanced ovarian cancer (Cancer Research Campaign Phase I/II Trials Committee).

Methylene dimethane sulphonate (MDMS), the first member of the homologous series of dimethane sulphonic acid esters, was administered to 19 patients with advanced epithelial ovarian cancer. All patients had received prior chemotherapy and in addition 3 had received prior radiotherapy. MDMS was given as an i.v. bolus injection at a dose of 125mg m-2 and repeated in a q35 day schedule. Ten patients received only one course, six two courses, two three courses and one four courses. The major toxicity was thrombocytopenia which was cumulative. Serious neutropenia did not occur and no infective episodes requiring i.v. antibiotics were seen. Seven patients experience hair loss and four nausea and vomiting. Sixteen patients were evaluable for response but no objective remissions were seen although three patients had stable disease lasting at least 8 weeks. MDMS is therefore not recommended for further trial in epithelial ovarian carcinoma.

Adult↗