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Biomedical subjects

S B Kaye

Publications and source records attributed to S B Kaye.

At least 145 records · Page 8Linked to original sources
PubMed1995

Referral patterns within Scotland to specialist oncology centres for patients with testicular germ cell tumours. The Scottish Radiological Society and the Scottish Standing Committee of the Royal College of Radiologists.

Details of 1123 patients registered in Scotland between 1983 and 1990 for testicular cancer under the Scottish Cancer Registration Scheme were obtained and compared with registrations within the five Scottish oncology centres. Some registration discrepancies were identified. Twenty-eight cancer registrations (2.5%) were coded to the wrong site, 29 patients seen at oncology centres had no cancer registration and 14 cancer registrations had the wrong histology. Five hundred and twenty-seven patients with testicular non-seminomatous germ cell tumours (NSGCT) and 567 with testicular seminoma were identified. Referral rates to specialist oncology centres for testicular germ cell tumours were measured by period and health board area of residence. For the whole study period 92% of NSGCT and 93% of seminoma patients were referred to specialist centres for treatment. Referral rates for different health board areas of residence were not significantly different. This study shows that within Scotland the majority of patients with testicular NSGCT and seminoma are referred to specialist centres, and suggests referral rates of around 92% are underestimates. Access is not related to area of residence.

Cancer Care Facilities↗
PubMed1995

A Scottish national audit of current patterns of management for patients with testicular non-seminomatous germ-cell tumours. The Scottish Radiological Society and the Scottish Committee of the Royal College of Radiologists.

A detailed casenote review was performed on all 65 patients registered with testicular non-seminomatous germ cell tumours (NSGCT) during 1989 under the Scottish Cancer Registration Scheme. Details of management at presentation and 2 years following diagnosis were recorded and analysed. In a small number of patients an unacceptable delay in diagnosis was noted. Variation was found in the frequency and type of investigations performed on patients placed on surveillance, types of chemotherapy regimens used and numbers of patients entered into trials. Three per cent of patients had a biopsy of the contralateral testis and 27% of patients defaulted from clinic attendance. Considerable variation in the management of testicular NSGCT in Scotland has been identified. The introduction of management guidelines should result in a more consistent approach to the care of these patients. Support, both financial and psychological, may reduce the unacceptable rate of default.

Adolescent↗
PubMed1995

A Scottish national mortality study assessing cause of death, quality of and variation in management of patients with testicular non-seminomatous germ-cell tumours. The Scottish Radiological Society and the Scottish Standing Committee of the Royal College of Radiologists.

A detailed casenote review was performed on 55 patients registered with testicular non-seminomatous germ cell tumours (NSGCT) between 1983 and 1988 under the Scottish Cancer Registration Scheme and who had died by 1992. Details of all aspects of clinical management relating to their NSGCT and death details were extracted and summarised. An assessment was made on whether the patients' management had been optimal. An analysis of 5 year survival rates by the five Scottish oncology centres demonstrated significant differences between centres (range 70.4-94.2; chi 2 = 14.46, d.f. = 4, P = 0.006). Some patients in all centres were assessed as having received suboptimal treatment, but two centres performed less well than the other three. There is a suggestion that the number of patients treated suboptimally decreases with increasing number of patients seen, but this does not reach statistical significance.

Adolescent↗
PubMed1995

Does delayed diagnosis or scrotal incision affect outcome for men with non-seminomatous germ cell tumours?

OBJECTIVE: To ascertain whether delayed diagnosis or type of orchidectomy affected outcome for men with non-seminomatous germ cell tumours (NSGCT). PATIENTS AND METHODS: The case notes of 454 men resident in the west of Scotland with a diagnosis of NSGCT between 1975 and 1989 were retrospectively reviewed. The clinical record was available for 442 (97%) and included information on time to diagnosis in 92% and diagnostic surgery in 97%. The study end-point for orchidectomy was loco-regional recurrence and for diagnostic delay was survival. RESULTS: A significant minority of men (10.4%) underwent a scrotal orchidectomy or had a scrotal incision before an inguinal orchidectomy (9.4%). More scrotal incisions were performed on patients under the care of general surgeons (28%) than of urologists (12.1%). Of the men who had scrotal surgery, one of 78 (1.3%; 95% CI, 0-4%) developed loco-regional disease as the initial site of recurrence, compared with none of 318 men undergoing inguinal orchidectomy. The median time to diagnosis was 3 months. There was no relationship between time to diagnosis and tumour extent at presentation. A diagnostic delay of > 3 months was associated with inferior survival in univariate analysis, but delayed diagnosis was not an independent influence on survival after adjustment for the major prognostic factors--tumour extent, year of diagnosis and treatment unit. CONCLUSIONS: These results suggest that scrotal incision is unlikely to affect the risk of loco-regional recurrence and that effective cytotoxic therapy has probably reduced the prognostic importance of delayed diagnosis on survival of men with NSGCT.

Adolescent↗
PubMed1995

Docetaxel (Taxotere) in the treatment of solid tumors other than breast and lung cancer.

Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) has been widely studied in phase II trials in Europe and in the United States in a range of solid tumors. This review examines its activity in diseases other than breast and lung cancer (which are reviewed elsewhere in this supplement). Seventeen separate trials in eight tumor types have been reviewed, including almost 500 evaluable cases. All studies involved the same schedule, ie, docetaxel 100 mg/m2 given over 1 hour every 3 weeks. Significant activity has been seen in several diseases. Response rates in ovarian cancer range from 17% to 37% (according to extent of prior therapy); in gastric and pancreatic cancer, response rates of 26% and 29% have been reported, despite the fact that these diseases are notoriously resistant to chemotherapy. Other tumor types in which activity has been seen include head and neck cancer (32% response rate), melanoma (17%), and soft tissue sarcoma (18%). With regard to toxicity, a major feature has been the development of fluid retention and skin toxicity; efforts to ameliorate this with premedication are under way. For the future, trials will examine combination schedules and will also assess the drug's activity compared with paclitaxel. Current data suggest that it possesses antitumor efficacy that is at least as broad, and there are examples in which preliminary information indicates superiority.

Antineoplastic Agents, Phytogenic↗
PubMed1994

Topoisomerase I and II activity in human breast, cervix, lung and colon cancer.

The identification of human DNA topoisomerases as cellular targets for active anti-cancer drugs has stimulated further interest in topoisomerase function in tumour biology. Topoisomerase I and II catalytic activity is detectable in many normal and malignant tissues. However, little is known about the expression of topoisomerases in most human solid tumours. The present study evaluated topoisomerase I and II activity in biopsy samples from 86 patients with breast, lung, cervix or colon cancers. Significant intra- and inter-tumour variation in topoisomerase expression was observed. Topoisomerase I activity was relatively high in cervix and colon tumours in comparison to lung and breast cancers. Topoisomerase II activity was high in cervix, colon and lung cancers relative to breast cancer. Topoisomerase I and II activity co-segregated in individual colon tumour samples, but no correlation was observed in cervix, lung or breast tumours. The large heterogeneity in both topoisomerase I and II activity within a tumour type suggests a mechanism for variable response to topoisomerase-directed therapy. The differences in activity between tumour groups suggest that the potential efficacy of inhibitors of topoisomerase I in colon and cervical tumours may be greater than in lung and breast tumours. Future in vivo evaluation is required to establish the clinical relevance of the observed heterogeneity in topoisomerase activity.

Breast Neoplasms↗
PubMed1994

Identification of a multidrug resistance modulator with clinical potential by analysis of synergistic activity in vitro, toxicity in vivo and growth delay in a solid human tumour xenograft.

Circumvention of multidrug resistance in vitro by resistance modulators is well documented but their clinical use may be limited by effects on normal tissues. We have compared four resistance modifiers, both in terms of modulation of doxorubicin sensitivity in vitro and toxicity in vivo, in order to determine whether it is possible to select agents with clinical potential. Verapamil, D-verapamil and quinidine are all maximally active in the multidrug resistant cell line at about 7 microM and are not cytotoxic at this concentration. The tiapamil analogue Ro11-2933 is a highly potent resistance modulator such that at only 2 microM sensitization is greater than is seen with the other modulators at 7 microM. Since the ID50 concentration for Ro11-2933 is 17.7 microM (5-12-fold less than the other modifiers) we have used isobologram analysis to demonstrate that the interaction with doxorubicin is supra-additive and cannot be explained by additive toxicity. This method of analysis also revealed that when resistance modulation is related to the cytotoxicity of the modulator itself, all four modulators show comparable activity. On the other hand, measurement of the acute toxicity in mice of the modulators did reveal differences. The LD10 for verapamil (51 mg/kg) was about one third of that for quinidine (185 mg/kg) and this is consistent with the known maximum tolerated plasma levels in patients. Furthermore, whilst epirubicin alone was unable to reduce the growth rate of a multidrug resistant human tumour xenograft, the addition of quinidine, but not verapamil, at the maximum tolerated dose did do so. D-Verapamil was only about half as toxic as racemic verapamil and this too is consistent with clinical observations. The LD10 for Ro11-2933 (152 mg/kg) was comparable with that for quinidine. In the human tumour xenograft model maximal growth inhibition was observed with the combination of epirubicin and Ro11-2933 (45 mg/kg) and this degree of growth inhibition was comparable to that obtained with epirubicin alone in the drug sensitive xerografts. Ro11-2933 had no measurable effects on the plasma or tumour pharmacokinetics of epirubicin. These results suggest that it is possible to predict the clinical potential of a resistance modulator. Furthermore, Ro11-2933 is a promising agent for use in the clinic since maximal resistance modulation in vivo is observed at about one third of the LD10 dose.

Animals↗
PubMed1994

A phase I-II study of N-(phosphonacetyl)-L-aspartic acid (PALA) added to 5-fluorouracil and folinic acid in advanced colorectal cancer.

N-(phosphonacetyl)-L-aspartic acid (PALA) inhibits the enzyme L-aspartic acid transcarbamoylase (ATCase) which is important in de novo pyrimidine synthesis. Low dosages of PALA modulate the in vitro activity of 5-fluorouracil (5-FU) and PALA (250 mg/m2) inhibits pyrimidine synthesis in patients. PALA (250 mg/m2 day 1) was combined with an established 5-FU/folinic acid (FA) regimen [FA (200 mg/m2 over 2 h days 2 + 3) and bolus and 22 h infusional 5-FU (300-500 mg/m2 days 2 + 3)] without the need for dose reduction of 5-FU or FA. 35 patients were entered. Treatment was well tolerated; 4/27 patients experienced > or = ECOG grade 3 toxicity at full 5-FU dosage (500 mg/m2 bolus/infusion). However, the response rate in 33 evaluable patients was only 6.1% [95% confidence intervals (C.I.) 0.2-21.8%]. Median response duration was short (4 months, 95% C.I. 3-6 months) and overall median survival was 10 months (95% C.I. 7-16 months). Although PALA (250 mg/m2) can be combined with full dosage 5-FU/FA, the combination has poor activity in colorectal cancer.

Adolescent↗
PubMed1994

Activity of docetaxel (Taxotere) in small cell lung cancer. The Early Clinical Trials Group of the EORTC.

Docetaxel (Taxotere) is a new cytotoxic compound with a broad spectrum of activity in preclinical studies. This paper reports a phase II trial in patients with previously-treated small cell carcinoma of the lung. 34 patients received 100 mg/m2 of docetaxel in an intravenous infusion given over 1 h every 21 days. Seven partial responses were reported (25% of 28 evaluable patients). Duration of response was 3.5-12.6 months. Toxicities were predominantly neutropenia, alopecia and asthenia. Docetaxel is a new compound with activity in previously-treated patients with small cell lung cancer, and is suitable for evaluation in combination with other cytotoxic drugs active in this disease.

Adult↗
PubMed1994

Docetaxel (Taxotere) in advanced renal cell cancer. A phase II trial of the EORTC Early Clinical Trials Group.

Docetaxel (Taxotere), an analogue of paclitaxel, was tested in a phase II study in advanced renal cell carcinoma. Consenting patients with measurable lesions, adequate organ functions and no prior chemotherapy received 100 mg/m2 of docetaxel as a 1-h infusion every 3 weeks. No premedication to avoid hypersensitivity reactions or nausea and emesis was given. 32 eligible patients received 100 treatment cycles. Short-lasting neutropenia was the dose-limiting toxicity. Acute hypersensitivity reactions (HSR), oedema and skin changes were other important side-effects. HSRs regressed spontaneously or were treated with antihistamines with or without corticosteroids. One partial remission was documented. At the dose and schedule used, docetaxel has only low activity against renal cell carcinoma.

Adult↗
PubMed1994

Docetaxel (Taxotere), a novel taxoid, in the treatment of advanced colorectal carcinoma: an EORTC Early Clinical Trials Group Study.

Docetaxel (Taxotere), a new semisynthetic taxoid, is a potentially important chemotherapeutic agent for the treatment of cancer. Forty patients with bidimensionally measurable advanced adenocarcinoma of the colon were treated with docetaxel 100 mg m-2 every 3 weeks as a 1 h infusion without routine premedication. Thirty-nine patients were eligible: 23 males and 16 females. Median age was 60 years (range 41-75) and WHO performance status 1 (0-2). Prior adjuvant chemotherapy was performed in four patients and prior radiotherapy in nine patients. Bidimensionally measurable disease sites included: liver in 26 patients, lymph nodes and abdominal/peritoneal masses in 13, lung/mediastinal masses in ten and subcutaneous nodes in four. The median number of cycles given was 2 (range 1-15). Thirty-three patients were evaluable for response. One patient (3%) achieved a complete response and two (6%) (95% confidence limits 0-14%) a partial response. Side-effects were similar to those observed in other studies. Docetaxel, given at this dosage and schedule, has minimal activity in the treatment of colorectal carcinoma.

Adult↗
PubMed1994

Bolus/infusional 5-fluorouracil and folinic acid for metastatic colorectal carcinoma: are suboptimal dosages being used in the UK?

Bolus/infusional 5-fluorouracil (5-FU) and folinic acid (FA) is reported to be highly active [partial response (PR) = 54%, median survival 18 months] in patients with metastatic colorectal carcinoma (MCCa). To confirm this level of activity, we conducted a retrospective analysis of 95 previously untreated patients with MCCa treated with FA by 2 h i.v. infusion (200 mg m-2) followed by 5-FU bolus/22 h i.v. infusion (300-500 mg m-2) on days 1 and 2 every 2 weeks. Thirty patients also received N-(phosphonacetyl)-L-aspartate (PALA), 250 mg m-2, 24 h prior to 5-FU/FA. In 81 evaluable patients, the response rate was low: PR = 11%, stable disease (SD) = 36% and median survival = 8 months. There was an improvement in survival with increased 5-FU dosage (500 mg m-2) [relative hazard (RH) = 0.38, 95% CI 0.21-0.70], controlled for age, primary site, PALA, liver function and performance status. Good performance status (PS 0 or 1) was also associated with improved survival (RH = 0.21, 95% CI 0.10-0.46). Response, survival and toxicity were not altered by the co-administration of PALA. Bolus/infusional 5-FU (500 mg m-2) and FA was well tolerated. WHO toxicities (grade 3) were: mucositis, 2%; diarrhoea, 14%; nausea and vomiting, 5%. In light of the apparent dose effect, poor response and low toxicity, we recommend that regimes incorporating higher 5-FU dosages are explored and prospectively validated before bolus/infusional 5-FU becomes accepted standard practice.

Adult↗
PubMed1994

A Cancer Research Campaign (CRC) phase II trial of CB10-277 given by 24 hour infusion for malignant melanoma.

The decarbazine analogue CB10-277 has been investigated for anti-tumour activity in a phase II study on malignant melanoma. Treatment was administered as a slow infusion of 12,000 mg m-2 over 24 h and repeated every 3 weeks. A total of 28 patients were entered into the study, of whom 23 were eligible for review. A total of 64 courses was given. There was one objective partial response in 22 patients assessable for response. The major toxicities were leucopenia and thrombocytopenia. CB10-277 in this schedule therefore does not appear to have major activity in melanoma.

Adult↗
PubMed1994

Molecular analysis of the topoisomerase II alpha gene and its expression in human ovarian cancer.

BACKGROUND: DNA topoisomerase II enzymes are key targets for the group of anti-tumour agents known as topoisomerase inhibitors. In general, cell lines which express high levels of topoisomerase II are sensitive to the cytotoxic effects of the topoisomerase poisons. The levels of topoisomerase II expression in tumour biopsies may therefore predict response to treatment with enzyme inhibitors. In the current study we have analysed ovarian tumours for expression of topoisomerase II alpha and genetic change at the topoisomerase II alpha locus on chromosome 17. MATERIALS AND METHODS: We have used methodology which allows the sequential extraction of protein and genomic DNA from the same biopsy sample to study the topoisomerase II alpha locus and the expression in ovarian cancer. Topoisomerase II alpha expression was quantified by Western blot analysis in 54 tumours. RESULTS: Topoisomerase II alpha expression was detected in 65% of ovarian tumours with a 16 fold range in level. In adenocarcinomas, the topoisomerase II alpha gene can become amplified due to its proximity to ERBB2 on chromosome 17q. Of 86 ovarian tumours studied only 1 had amplification of ERBB2 and none had amplification of topoisomerase II alpha a sequences. CONCLUSIONS: Topoisomerase II alpha expression was detected in ovarian carcinomas by Western blot analysis. A sixteen-fold range in expression was detected with significantly higher levels of topoisomerase II alpha expression in advanced stage IV and grade III tumours. Molecular analysis of the topoisomerase II alpha locus failed to reveal any gross genetic alterations which could account for the variation in levels of expression.

Adenocarcinoma↗
PubMed1994

Phase II studies of Elsamitrucin in breast cancer, colorectal cancer, non-small cell lung cancer and ovarian cancer. EORTC Early Clinical Trials Group.

PURPOSE: To test the antitumor activity of Elsamitrucin in metastatic cancer of the breast, colon and rectum, non-small cell lung and ovary. PATIENTS AND METHODS: Eligibility required histologically proven cancer. Patients with colorectal or non-small cell lung cancer could not have received prior chemotherapy. Patients were entered if WHO PS was < or = 2 and organ functions were normal. Treatment consisted of Elsamitrucin 25 mg/m2/week given as a 5-10 min infusion for at least 3-6 weekly doses. RESULTS: One hundred and five patients entered the studies, 97 were eligible, 94 are evaluable for toxicity and 75 for response. Toxicity mainly consisted of mild nausea/vomiting, and less frequently reversible hepatotoxicity and malaise. No objective responses were seen. CONCLUSION: Elsamitrucin at this dose and schedule is not an active drug in metastatic breast cancer, colorectal cancer, non-small cell lung cancer or ovarian cancer.

Adolescent↗
PubMed1994

Docetaxel (Taxotere): an active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. EORTC Early Clinical Trials Group.

BACKGROUND: Docetaxel (Taxotere) is a new cytotoxic agent acting as a promoter of tubulin polymerisation with broad spectrum antitumor activity in preclinical testing. Phase I clinical trials have shown promising activity of docetaxel in patients with breast, ovarian and lung carcinomas. The objective of this open multicentre phase II study was to determine the efficacy and tolerability of this agent in patients with head and neck cancer. PATIENTS AND METHODS: Patients with proven advanced and/or recurrent squamous cell carcinoma of the head and neck without prior chemotherapy for advanced disease were eligible for this trial. Docetaxel was given at a dose of 100 mg/m2 as a 1 hour infusion every 3 weeks. Dose reductions were performed according to hematological and non-hematological toxicities. No pre-medication was given to prevent hypersensitivity reactions. RESULTS: Fourty-three patients entered this trial: 39 patients were evaluable for toxicity and 37 patients were evaluable for response. Sixty-five percent of the patients had locoregional disease, 28% had metastatic disease, and 7% had both. Twenty-five percent of the patients had previously received neo-adjuvant cisplatin-based chemotherapy. A total of 166 docetaxel courses were administered. The most frequent side-effects associated with docetaxel were alopecia (90% of the patients), asthenia (69% of the patients) and short lasting neutropenia (grade 3-4 neutropenia in 61% of the courses). Fifty-four percent of the patients experienced skin toxicity, 23% experienced hypersensitivity reaction, and 31% developed peripheral edema. Ten partial and 2 complete responses were observed, yielding a response rate of 32% (95% confidence interval 17%-47%). CONCLUSION: Docetaxel is an active drug in patients with advanced squamous cell carcinoma of the head and neck.

Adult↗
PubMed1994

Primary mediastinal germ cell tumour and acute monocytic leukaemia occurring concurrently in a 15-year-old boy.

This report describes the case of a 15-year-old boy who presented with a primary mediastinal germ cell tumour and while receiving chemotherapy developed an acute monocytic leukaemia. The occurrence of these conditions simultaneously is extremely rare, and the possible shared aetiology is discussed. Also, the role of the chromosome marker i(12p) in the diagnosis of germ cell tumours is examined.

Adolescent↗