Search PubMed⌕ Search

Biomedical subjects

R T Oliver

Publications and source records attributed to R T Oliver.

At least 37 records · Page 2Linked to original sources
PubMed2000

A medical research council randomized trial of single agent carboplatin versus etoposide and cisplatin for advanced metastatic seminoma. MRC Testicular Tumour Working Party.

The UK Medical Research Council conducted this trial of carboplatin chemotherapy in advanced seminoma to compare single agent carboplatin with a standard combination of etoposide with cisplatin. The use of single agent carboplatin was expected to be associated with reduced toxicity. A total of 130 patients with advanced seminoma were randomly assigned to treatment with either single agent carboplatin (C) at a dose of 400 mg/m(2)to be corrected for glomerular filtration rate outside the range 81-120 ml min(-1)and to be administered on day 1 of a 21 day cycle to a total of 4 cycles or to etoposide + platinum (EP). The trial was designed as an equivalence study aiming to exclude a reduction in the 3-year progression-free survival in patients allocated to carboplatin of between 10 and 15%, requiring initially a target accrual of 250 patients (90% power significance level 5% (one-sided)). The trial closed after 130 patients had been randomized following recommendation by an independent data monitoring committee. At a median follow-up time of 4.5 years, 81% of patients had been followed up for at least 3 years and 19 patients have died. The estimated PFS rate (95% Confidence Intervals (CI)) at 3 years was 71% (60-82%) in patients allocated C and 81% (71-90%) in those allocated EP; the 95% CI for the difference in 3 year PFS was - 6% to +19%. The hazard ratio of 0.64 (95% CI 0.32-1.28) favoured EP but the difference was not statistically significant (log rank chi-squared = 1.59 P = 0.21). The 3-year survival rate was 84% (75-92%) in those allocated C, and 89% (81-96%) in those allocated EP. The hazard ratio for survival was 0.85 with 95% CI, 0.35-2.10, log rank chi-squared = 0.12, P = 0.73. The trial has not demonstrated statistically significant differences in the major survival endpoints comparing single agent carboplatin with a combination of etoposide + cisplatin. This cannot be taken as an indication of equivalence since the limited size of this trial rendered it unable to exclude a 19% lower progression-free survival and survival in those treated with single agent carboplatin which would be important clinically. Standard initial chemotherapy for advanced seminoma should be based on cisplatin combinations and the role of carboplatin awaits the outcome of further studies.

Antineoplastic Agents↗
PubMed2000

Should high-dose chemotherapy be used to consolidate second or third line treatment in relapsing germ cell tumours?

Thirty consecutive patients with relapsing germ cell tumours (GCT) were treated with induction chemotherapy and high-dose chemotherapy consolidation (HDCT). Overall, 47% were progressionfree and 53% were alive with a median follow up of 40 months. Initially, HDCT was given as consolidation of third line VIP (etoposide/ifosfamide and cisplatin), following failure of a weekly cisplatin regimen. During 1995, paclitaxel was introduced into second line therapy with cisplatin and ifosfamide (TIP), with immediate consolidation using HDCT. At the same time the carboplatin dosing calculation was changed and an area under the curve (AUC) formula rather than by mg/m2 was used to calculate this. The main determinant of post-treatment renal dysfunction was pretreatment renal function rather than the AUC dose of carboplatin. Only a raised LDH prior to induction or absolute refractory disease in response to induction chemotherapy predicted poor survival following HDCT. In patients relapsing following HDCT, the outcome was poor with many patients relapsing in the central nervous system and other new sites of disease. Further responses were seen to chemotherapy or radiotherapy but these were not sustained. The failure to improve results when HDCT was used as second line rather than third line chemotherapy consolidation was disappointing and adds to further uncertainty of the role of this approach as far as timing and the ideal preparative regimen are concerned.

Adolescent↗
PubMed2000

Current opinion in germ cell cancer 2000.

Despite its relative rarity compared with the common adult cancers, scientific and clinical interest in germ cell cancer is increasing. From the point of view of epidemiology, the controversy about the relative importance of intrauterine versus postpubertal risk factors has continued. Evidence to support the importance of intrauterine factors comes from reports from Norway, Canada, and the US, confirming the Danish observation that the rising incidence of germ cell cancer is linked to a birth cohort effect; evidence in support of the importance of postpubertal risk comes from three case/control studies demonstrating increased risk linked to postpubertal exposures such as pesticides, plastics, electromagnetic radiation, trauma, and infections. There has been increasing interest in human endogenous retrovirus K10 as a possible factor explaining genetic susceptibility and providing a linkage between the two groups of risk factors. In cytogenetics, progress was reported in identifying the deletion point of the suspected tumor suppressor gene responsible for the i12p marker chromosome abnormality and development of FISH probes for diagnostic purposes. In molecular biology, the importance of DNA repair deficiency in normal germ cells as a factor in the exquisite chemosensitivity of germ cell cancer has been high-lighted by a report demonstrating a low level of the xeroderma pigmentosa group A (XPA) protein and induction of resistance in vitro by adding XPA. In the clinic, progress in positron emission tomography scanning and laparoscopic lymph node staging are leading to changes in outlook on management of stage 1 cases and patients with small residual masses postchemotherapy. Salvage chemotherapy regimens integrating dose dense and vertical dose intensification strategies reported 60% progression-free survival. New drugs such as gemcitabine demonstrated continued therapeutic potential for chemotherapy in these tumors. A report demonstrating the inadequacies of hormone replacement after bilateral orchidectomy and a report of the first child born after testis-conserving therapy highlight the need for more attention to testis conservation as a quality of life issue. With the cure rates so high, the need for central referral is once again debated both for stage 1 and metastatic disease. With new ways of defining poor risk stage 1 patients and reports on impact of experience highlighting the worse outcome of patients treated in centers treating small numbers, views on this issue remain clearcut.

Clinical Trials as Topic↗
PubMed2000

Advanced testicular cancer presenting with phlegmasia cerulea dolens.

A case of fulminating deep venous thrombosis secondary to invasion of the inferior vena cava is described in a 45 year old man presenting with a germ cell tumour. Despite aggressive supportive care and emergency chemotherapy his late presentation caused his death. The case highlights the necessity for increased public education of the attendant risks in delayed presentation with a testicular lump.

Fatal Outcome↗
PubMed2000

CT assessment of tumour response to treatment: comparison of linear, cross-sectional and volumetric measures of tumour size.

Changes in cross-sectional area are currently used to assess tumour response to treatment. The aims of this study were to validate a helical CT technique for volume determination using a series of phantoms and to compare tumour responses indicated by one-, two- and three-dimensional measures of tumour size change in patients treated for germ cell cancer or lymphoma. All studies were performed on an IGE HiSpeed Advantage helical CT scanner with an Advantage Windows workstation. Phantom volumes were calculated using volume reconstruction software and compared with reference volumes determined by water displacement. 20 lymph node masses were studied on serial CT scans in 16 patients treated with chemotherapy for germ cell cancer or lymphoma. For each lesion the maximum diameter, maximum cross-sectional area and volume were determined before and after treatment. Tumour response was assessed using the standard World Health Organisation criteria (i.e. changes in cross-sectional area) and the newly proposed unidimensional response evaluation criteria in solid tumour (RECIST). The CT volume measurement error was 1.0-5.1% for regularly shaped phantoms larger than 35 cm3. In the assessment of treatment response there was 90% agreement between one-dimensional (1D) and two-dimensional (2D) measurements and 100% agreement between 2D and three-dimensional (3D) measurements. CT volume measurements are accurate and reproducible, particularly for larger structures. Assessment of tumour response using 1D, 2D and 3D measures had limited influence on the classification of treatment response. However, the impact of CT assessment of tumour response using 1D, 2D and 3D measurements on clinical decisions and patient outcome remains to be determined.

Adult↗
PubMed2000

Testosterone: its role in development of prostate cancer and potential risk from use as hormone replacement therapy.

Evidence from studies in patients with prostate cancer of intermittent hormone therapy combined with results from rechallenge of hormone resistant patients with testosterone demonstrate that the majority of prostate cancers retain a similar degree of dependence on male sex hormone milieu as normal prostate cells. Yet there has so far been no conclusive evidence, despite 34 studies, that levels of circulating testosterone in individuals developing prostate cancer are higher than in controls. The aim of this article was to critically evaluate this evidence and seek clues to other mechanisms whereby sex hormones could influence the development of prostate cancer. Additionally, epidemiological data were examined to investigate the interplay between sex hormone levels and environmental factors to help understand the development of prostate cancer and identify a safe way to provide hormone replacement therapy (HRT). Three overviews provide similar evidence that there is no significant difference in mean testosterone levels between patients and controls. However in the most recent review of studies, though there was no difference in means between cases and controls, there was a significant risk (adjusted odds ratio 2.34) for individuals identified by comparing incidence of prostate cancer in men in the upper and lower quartile of testosterone level. This report, taken with epidemiological data demonstrating that prostate cancer risk is increased by early age of onset of sexual activity and multiple nonspecific sexually transmitted diseases (STDs), has led to the hypothesis that the link between sex hormones and prostate cancer is indirect. Those individuals with high testosterone levels were more at risk of acquisition of multiple nonspecific STDs. This promotes transformation of prostate cells and damage to Leydig cells in the testis leading to there being no difference in testosterone compared with controls by the time the tumour is diagnosed. Because of the observed relationship between testosterone and prostate cancer development there has been anxiety about marketing HRT for men. Two observations support the view that the prostate cancer risks from use of testosterone hormone replacement may not be as great as first feared. Firstly, prostate cancers arising in men with low serum testosterone levels are more malignant and frequently nonresponsive to hormones. Secondly, breast cancers diagnosed in women on HRT though increased in number are less malignant possibly because of enhanced sensitivity to hormone therapy, and the situation may prove to be analogous with prostate cancer and testosterone replacement.

Animals↗
PubMed2000

Intermittent hormone therapy: its potential in early prostate cancer and intra-epithelial neoplasia.

This paper reviews results from a pilot study of 40 patients entered on intermittent hormone therapy having achieved a PSA complete remission. The median time to clinical progression and need for further hormone therapy was 14 month; and 88% of patients retreated are progression-free at 1 year and an overall 88% are alive at 3 years. There was some evidence that there was slower progression to require treatment in older patients and those who had been on treatment for more than 15 months. Since the overall survival in this study is better than that of patients with M0 disease on hormone therapy in the immediate arm of the MRC immediate vs. deferred therapy study, it is thought reasonable to justify progression to a randomised trial. This should also include all patients failing to achieve PSA complete remission in order to examine the issue of whether androgen withdrawal is required in the terminal treatment phase of hormone resistance patients to keep the hormone sensitive clone under control.

Androgen Antagonists↗
PubMed1999

Sixty percent salvage rate for germ-cell tumours using sequential m-BOP, surgery and ifosfamide-based chemotherapy.

BACKGROUND: In germ-cell tumours (GCT), there is continuing controversy over the relative merits of dose dense therapy (increased frequency over a given time) versus vertical intensification (increased dose per fraction). The value of using a cisplatin-based dose dense approach in the salvage setting has not been documented and in addition the role of methotrexate remains uncertain. This paper reviews results from our investigations of these issues. PATIENTS AND METHODS: Between 1987 and 1996, 65 patients with relapsing or refractory germ-cell tumour received weekly m-BOP (methotrexate, bleomycin, vincristine and cisplatin) as salvage therapy. Residual masses were excised if possible and patients progressing after this received cisplatin and ifosfamide based chemotheraphy with or without high dose chemotherapy (HDCT) consolidation. RESULTS: With a median follow-up of 33 months, 34% are progression free following m-BOP, 11% who had surgery for residual masses which showed viable cancers are progression free. A further 15% who progressed following m-BOP with or without surgery were rendered progression free by third-line therapy. CONCLUSIONS: The use of m-BOP as second line therapy with deferment of cisplatin and ifosfamide based treatment to third line therapy with consolidation of third line responses with HDCT, leads to an overall progression-free survival of 60%. It does not appear that M-BOP prejudiced the response to third line therapy suggesting a lack of cross resistance. The potentially lower risk of leukaemia and infertility from m-BOP requires further evaluation.

Adolescent↗
PubMed1999

Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumours.

The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. 'Progressive disease' included patients who had progressed after a previous partial or complete remission as well as patients who failed primary therapy. Salvage chemotherapy consisted of 'conventional' platinum-based chemotherapy. Prognostic factors for survival were assessed by uni- and multivariate analyses. The resulting prognostic model was validated in an independent data set of 66 similar patients. For all 164 patients the median time from start of induction chemotherapy to progression was 10 months (range: 0-99). Thirty-eight (23%) patients relapsed after 2 years. The 5-year survival rate for all progressing patients was 30% (95% confidence interval 23-38%). In the univariate analysis the following factors most importantly predicted a poor prognosis: progression-free interval < 2 years: initial poor prognosis category (MRC criteria), < CR to induction chemotherapy, initial treatment early in the 1980s and treatment given at a 'small' centre. Three prognostic factors remained in the multivariate analysis: progression-free interval, response to induction treatment and the level of serum human chronic gonadotrophin (hCG) and alpha fetoprotein (AFP) at relapse. One hundred and twenty-four patients could be classified on the basis of these characteristics, Those patients with progression-free interval < 2 years, < CR to induction chemotherapy and high markers at relapse (AFP >100 kU l(-1) or hCG >100 IU l(-1)) formed a poor prognosis group of 30 patients, none of whom survived after 3 years. Patients with at most two of these three risk factors formed a good prognosis group of 94 patients (76%) with a 47% (37-56%) 5-year survival. Thirty-eight patients from the good prognosis group with a progression-free interval of >2 years had a 2-year survival of 74% (60-88%) and 5-year survival of 61%. These prognostic groups were validated in the independent data set, in which 5-year survival rates in the good and poor risk groups were 51% and 0% respectively. One-third of patients progressing during or after platinum-based induction chemotherapy for metastatic germ cell malignancy may be cured by repeated 'conventional' platinum-based chemotherapy. Good prognosis parameters are: progression-free interval of > 2 years, CR to induction treatment and normal or low serum markers at relapse (hCG < 100 IU l(-1) and AFP < 100 kU l(-1)). The results of high-dose salvage chemotherapy should be interpreted on the background of these prognostic factors.

Adolescent↗
PubMed1999

Risk factors for testicular germ cell tumours by histological tumour type. United Kingdom Testicular Cancer Study Group.

There are two main histological groups of testicular germ cell tumours, which may have different risk factors. Some authors have analysed potential risk factors by histological group but few consistent differences have been identified. In this paper we examine risk factors for pure seminoma and other tumours using data from the United Kingdom case control study of testicular cancer. Seven hundred and ninety-four cases were included in the study, each with a matched control; 400 cases had pure seminoma tumours, and 394 had other testicular tumours. The risk of seminoma associated with undescended testis was slightly higher than that for other tumours (odds ratio of 5.3 compared with 3.0). When split at the median age at diagnosis, this difference was greater in men aged 32 and over (odds ratio of 11.9 compared with 5.1) than in the younger men (3.0 compared with 2.5). Risks associated with testicular or groin injuries were higher in the non-seminoma group, as was the risk for a history of sexually transmitted disease. The protective effect of a late puberty was more marked for tumours of other histologies. Some differences were also detected for participation in sports. Whilst some of the differences detected may have arisen by chance, the stronger association between undescended testis and pure seminoma has been identified by a number of other studies and may reflect a genuine difference in aetiology.

Adult↗
PubMed1999

The management of residual masses after chemotherapy in metastatic seminoma.

OBJECTIVE: To review our experience in management of residual masses after chemotherapy for metastatic seminoma. PATIENTS AND METHODS: The study comprised a review of 107 patients with metastatic seminoma, treated with initial chemotherapy from 1978 to 1996. Forty-three patients had residual masses detected by computed tomography after chemotherapy, while 64 achieved a complete response. Residual masses were classified radiologically as <3 cm or >/=3 cm and as well- or poorly defined. Of the patients with residual masses, 19 underwent surgery, while 24 were observed. RESULTS: Viable cancer was present in six of 11 patients with well-defined residual masses of >/=3 cm (positive histology in three of six undergoing surgery and site relapses in three of five observed), one of 14 patients with poorly defined masses of >/=3 cm (negative histology in nine undergoing surgery and site relapse in one of five observed), and in none of 17 patients with residual masses of <3 cm (negative histology in four undergoing surgery and no site relapses in 13 observed; one additional patient in this group died from treatment complications). CONCLUSION: Patients with a complete response after chemotherapy, a residual mass of <3 cm and a poorly defined residual mass of >/=3 cm can be observed, reserving intervention for recurrent or progressive disease. Well-defined residual masses of >/=3 cm should be resected because there is a 55% likelihood of persistent tumour.

Humans↗
PubMed1999

Germ cell cancer.

The publication of the proceedings of Fourth Workshop on Carcinoma in situ was an impressive leap in our understanding of the interaction between prenatal and postpubertal factors in the development of germ cell cancer as well as increased insight into the molecular events that are involved in the development of these tumors. From this work, physicians are increasingly accepting that estrogen-mediated prenatal priming of germ cells generates a predisposition to postpubertal cyclin D2-driven initiation of full mitotic cell cycle replication of a tetraploid p53-expressing meiotically arrested pachytene spermatocyte that is under increased gonadotrophin drive because of testicular atrophy inducing events. From this new knowledge, new markers, eg, FGF4, CD30, and OCT-4, of embryonal carcinoma cells are identifying alternative ways of identifying poor risk tumors and leading to renewed interest in study of histopathology of these tumors. With greater attention to late events and increasing confirmation that chemotherapy is better than radiation even in seminoma and that seminoma is more chemosensitive than nonseminoma, a renewed clinical need exists for improved pathologic definition to reduce unnecessary usage of chemotherapy and maximize its benefits. With the failure of vinblastine, ifosfamide, and cisplatin to show any benefit over BEP (bleomycin, etoposide, and cisplatin) in the Southwest Oncology Group trial, re-examination of approaches to treatment of poor risk disease is emphasized as the priority for future trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

A lesson in the management of testicular cancer in a patient with a solitary testis.

Five per cent of patients with germ cell tumours of the testis will develop a further tumour in the contralateral testis. Standard treatment in such cases is a second orchidectomy, resulting in infertility, hormone replacement, and psychological morbidity. In this case report we explore the role of testis conservation in these patients and also show that there is a risk of removing a potentially normal testis if a histological diagnosis is not sought prior to orchidectomy.

Adult↗
PubMed1999

Profile of placental alkaline phosphatase expression in human malignancies: effect of tumour cell activation on alkaline phosphatase expression.

Cellular alkaline phosphatases (ALP) are increasingly recognised as important markers for monitoring tumour cell behaviour in human malignancies. Colorimetric, flow-cytometric, and immunocytochemical assays were employed to assess the influence of activation on expression of cellular ALP in human tumour cell lines. The results showed the following: (1) Testis tumour biopsies (16/16) unlike bladder (0/14) and head and neck (0/16) tumours showed positive staining for ALP, particularly the placental type, i.e. PLAP, although this was not always present on all the cells of non-seminoma biopsies. (2) The intensity of ALP expression differed widely in tumour cell lines. Based on biochemical analysis, the profile of ALP fell into two categories: (a) low expressing (MW 70 kD, placental type ALP) like Hep2 and KB lines, and (b) those expressing both low and high molecular (MW 95 kD) bands like testis lines Tera II and Ep2102. In all cases treatment of tumour cell lysates with heat prior to biochemical analysis showed the disappearance of the higher and sharpening of the lower molecular weight ALP band. (3) Exposure of tumour cells to epidermal growth factor (EGF) expressing EGF receptor led to a decreased ALP expression by as much as 54% as assessed by biochemical or flow-cytometric techniques. These data demonstrated that testis tumour tissues and cell lines expressed ALP which were different from others. The data also showed that exposure of tumour cell lines expressing EGFr to EGF resulted in suppression of ALP expression. These observations are consistent with the notion that EGFr and PLAP expression may be taken as a marker of proliferation and differentiation in human malignancies, respectively.

Alkaline Phosphatase↗
PubMed1999

Standardization and potential use of HPLC for detection of cellular placental alkaline phosphatase using established tumour cell lines and fresh tumour biopsies.

Placement alkaline phosphatase (PLAP) is one of the cellular phosphatases (ALP) expressed in patients with testis cancers, particularly in seminomas. Using various techniques including Western blot and high-performance liquid chromatography (HPLC) systems and ATC2, a newly developed specific anti-PLAP monoclonal antibody (Mab), the presence of active form of PLAP in lysates prepared from testis tumour fragment and tumour cell lines, was studied. This was carried out following isolation of PLAP from biological samples using CNBr Sepharose-conjugated ATC2 beads. The results showed that: (1) The target for the newly developed Mab ATC2 was PLAP. (2) The ATC2-conjugated bead system was an efficient method for isolating pure PLAP. (3) Diethylamine (DEA), in contrast to urea and glycine, was the most efficient for separation of PLAP from ATC2-conjugated beads, as the isolated molecule did not lose any phosphatase activity and there was very little uncoupling of the ATC2 Mab from the beads. (4) ATC2-conjugated CNBr beads could pick up PLAP from a solution containing standard PLAP and lysates prepared from tumour cell lines or testis tissue fragments positive for the PLAP. (5) HPLC profile of testis tumour lines and testis tumours showed two distinct peaks with ALP activity, one at retention time 7-8 min (corresponding to 95 kDa molecule) and one at 12-13 min corresponding to 70 kDa molecule). These data demonstrated the potential use of various biochemical methods in combination with HPLC for isolation of the fully functional molecules with ALP activity from different samples including lysates prepared from patients with testis cancer. The nature of ALP activity at 95 kDa is being investigated as no such molecule has been reported previously. These techniques might have an important implication for an early detection of germ cell tumours, particularly in patients with equivocal ultrasound.

Alkaline Phosphatase↗
PubMed1998

Postchemotherapy residual masses in germ cell tumor patients: content, clinical features, and prognosis. Medical Research Council Testicular Tumour Working Party.

BACKGROUND: In a retrospective study that included a detailed histopathologic review, the clinicopathologic features of patients with germ cell tumors (GCT) and resectable residual masses after chemotherapy were assessed. METHODS: Histologic material from 153 patients was available for review. Recorded details included primary histologic diagnosis, location, size and number of metastases, marker levels before and after chemotherapy, and completeness of surgical excision. A median of seven histologic sections per resection were reviewed by two pathologists independently (and together when disagreement occurred). In each case, details were recorded regarding fibrosis, necrosis, hemorrhage, embryonal carcinoma (undifferentiated teratoma), yolk sac tumor, choriocarcinoma (trophoblastic tumor), differentiated teratoma (mature and immature), dysplasia in somatic tissues, and non- germ cell tumor (GCT) malignancies. The percentage of the sample that each of these components comprised was also estimated. RESULTS: The median postchemotherapy follow-up time was 7 years, and 38 of 153 patients (25%) experienced disease progression. In a multivariate analysis, incomplete resection of all residual masses (in 38 patients) and the presence of malignant elements (in 23 patients) were independent risk factors for progression. In the subset of patients in whom all masses were completely resected, the presence of embryonal carcinoma (undifferentiated teratoma) was the single most significant risk factor for progression. Seven percent of patients had this factor, which was associated with a 2-year progression free survival rate of 12.5%, compared with 88.0% where this component was absent. CONCLUSIONS: Progression free survival can be predicted well by the completeness of excision of residual masses and the presence of malignant germ cell elements. The latter confers a relatively poor prognosis even if all of these elements are completely resected.

Disease-Free Survival↗