Search PubMed⌕ Search

Biomedical subjects

R H Begent

Publications and source records attributed to R H Begent.

At least 127 records · Page 7Linked to original sources

The clinical value of imaging with antibody to human chorionic gonadotrophin in the detection of residual choriocarcinoma.

Choriocarcinoma can be imaged by external scintigraphy after intravenous administration of radiolabelled antibody directed against human chorionic gonadotrophin (HCG). The purpose of this study was to investigate whether antibody imaging was sufficiently sensitive and specific to improve the selection of patients for surgical resection of localised deposits of drug resistant or recurrent choriocarcinoma. Eighteen patients with raised serum HCG concentrations in whom the site of tumour was not known were investigated by antibody imaging and conventional imaging methods. When the tumour appeared localised, resection was attempted. Tumour was found at all sites in which both antibody imaging and conventional imaging methods were positive. Antibody imaging gave false positive results in 2 of 18 patients and false negatives in 5. Computerised tomography was false positive in one case and false negative in 2. In these patients, antibody imaging gave true negative and true positive results respectively. Of 8 patients with positive antibody imaging in whom resection was attempted, 5 achieved sustained complete response with up to five years follow up. It is concluded that antibody imaging is useful in selection of patients for surgery in drug resistant or recurrent choriocarcinoma.

Antibodies↗

Treatment of patients with poor prognosis anaplastic germ cell tumours (AGCT) of the testis and other sites.

Between 1977 and 1986, 170 male patients with anaplastic germ cell tumours (AGCT) completed chemotherapy with POMB/ACE (platinum, vincristine (oncovin), methotrexate, bleomycin, actinomycin D, cyclophosphamide and etoposide). By increasing the number of courses of POMB in 1979 we have been able to compensate for adverse prognostic factors. Since then each patient has received a minimum of three courses of POMB and 139 patients have completed therapy with an overall survival of 89%, and for those patients who had not received prior radiotherapy the survival is 92%. By increasing the number of courses of POMB, the initial serum concentrations of human chorionic gonadotrophin (hCG greater than 50,000 IU/I) and/or alpha-fetoprotein (AFP greater than 500 kU/l) have ceased to be poor prognostic variables. Neither stage at presentation nor the volume of metastatic disease is a major adverse prognostic variable using this chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Fertility after chemotherapy for male and female germ cell tumours.

Gonadal function was assessed in fifty-nine men and thirty-one women who had successfully completed chemotherapy with the POMB/ACE regimen for germ cell tumours. Seventeen (81%) of the twenty-one men who had not received paraaortic radiotherapy, whose original tumour bulk was less than 5 cm and whose duration of chemotherapy was less than 6 months, recovered spermatogenesis compared with twelve (32%) of thirty-eight patients who had either larger tumour masses or longer courses of chemotherapy, or both. All but one of the seventeen women in whom menstruation could have been expected to recur are now menstruating. This study suggests that the great majority of patients treated with POMB/ACE chemotherapy for germ cell tumours will recover fertility.

Adolescent↗

Fertility after chemotherapy for ovarian germ cell tumours.

Gonadal function was assessed in 17 women who successfully completed chemotherapy with the POMB/ACE regimen (cisplatin, vincristine [Oncovin], methotrexate, bleomycin/actinomycin D, cyclophosphamide, etoposide) for ovarian germ cell tumours, and had a remaining ovary and uterus. A 20-year-old girl has not yet recovered menstruation 5 months off chemotherapy. All the remaining women whose mean age at start of chemotherapy was 21 (9-38) are now menstruating with a median time of recovery of 41/2 months after completion of chemotherapy. Five women have so far conceived after chemotherapy resulting in three full term normal deliveries of healthy infants, one termination of pregnancy, two miscarriages and one continuing pregnancy. Gonadal function does not appear to be permanently impaired in the majority of patients receiving POMB/ACE chemotherapy for ovarian germ cell tumours.

Adolescent↗

Use of second antibody in radioimmunotherapy.

In this study, a second antibody was directed against the first antitumor antibody to accelerate clearance of the 131I-labeled first antibody and improve tumor to normal tissue ratios of radioactivity. The value of this method in improving the therapeutic index of radioimmunotherapy with 131I-antibody to CEA has been investigated in nude mice bearing xenografts of human colon carcinoma and in 5 patients with colorectal cancer. The xenografts did not become saturated with anti-CEA as the administered dose was increased to therapeutic levels. At these high dose levels, the second antibody increased tumor to blood ratios to a maximum of 155:1, 48 times the level in controls that did not receive the second antibody. In 5 patients given 50 mCi of anti-CEA, there was no significant toxicity with the second antibody; clearance of radioactivity was accelerated; and tumor imaging was enhanced. The second antibody appears to have the potential to improve the therapeutic index of radioimmunotherapy.

Animals↗

The value of carcinoembryonic antigen in clinical practice.

Carcinoembryonic antigen has been investigated as a tumour marker for over 20 years. It is not completely tumour specific but results can be used in decision making in certain well defined clinical situations. The most important is as a serum tumour marker and for radioimmunolocalisation in follow up of colorectal cancer.

Body Fluids↗

Successful management of metastatic and primary germ cell tumors in the brain.

Nine men and one woman with brain metastases from nonseminomatous germ cell tumors have been treated between 1977 and 1984. All the men had lung metastases. Nine patients had elevated serum values of human chorionic gonadotrophin (HCG), the level was greater than 40,000 IU/l in seven. They were treated with sequential combination chemotherapy either POMB/ACE or EP/OMB in which the methotrexate was given at a dose of 1 g/m2 and intrathecal methotrexate was given during courses not containing intravenous methotrexate. Eight of ten patients are alive, off treatment with no evidence of active disease, of whom five have been in remission and off treatment for more than 18 months. Two patients with primary intracranial nonseminomatous germ cell tumors were treated in a similar fashion. One patient died from enlargement of differentiated teratoma; the other is alive 9+ months off treatment with no evidence of disease. These results, which are better than any previously reported, indicate that chemotherapy is the preferred treatment of primary or metastatic nonseminomatous germ cell tumors of the brain and that only rarely will these patients benefit from surgery or radiotherapy.

Adolescent↗

Radioimmunolocalization and selection for surgery in recurrent colorectal cancer.

The value of radioimmunolocalization (RIL) of cancer depends on its performance in situations where the result determines the choice of management. A rise in serum carcinoembryonic antigen (CEA) values after apparently curative resection of colorectal cancer implies localized, resectable recurrence in some patients and widespread unresectable tumour in others. This study investigated the ability of RIL with radiolabelled antibody to CEA and a novel numerical method for analysis of results to determine the extent of disease in 31 patients with raised serum CEA but no physical signs of recurrence. Surgical exploration or conventional radiology later confirmed the presence of tumour in 94 per cent of sites which were positive by RIL. Negative RIL predicted the absence of disease in 53 per cent of patients. The investigation could discriminate between localized and disseminated disease and often performed better than conventional radiology. RIL appears useful in selection of patients for second look laparotomy.

Carcinoembryonic Antigen↗

Is ectopic production of human chorionic gonadotrophin (hCG) or alpha fetoprotein (AFP) by tumours a marker of chemosensitivity?

We have treated eight patients with various tumours producing hCG or AFP with the high risk gestational choriocarcinoma regimen EMA/CO. Marker response was seen in two of three tumours producing AFP and in all of five tumours producing hCG. Three further patients were treated with EpPt/OMB, a regimen used in relapsed germ cell tumors. All responded biochemically. All complete biochemical responses were accompanied by anatomical response. These responses may reflect particular sensitivity in the marker producing tumours and marker measurements would identify this subgroup. These findings do not preclude the possibility that these cytotoxic regimens may have activity against a wide range of solid tumours.

Antineoplastic Combined Chemotherapy Protocols↗

Current optimum management of anaplastic germ cell tumours of the testis and other sites.

Between 1977 and 1985, 149 male patients with anaplastic germ cell tumours (AGCT) completed chemotherapy with POMB/ACE (platinum, vincristine (oncovine), methotrexate, bleomycin, actinomycin D, cyclophosphamide and etoposide). By increasing the number of courses of POMB in 1979, we have been able to compensate for adverse prognostic factors. Since then each patient has received at least three courses of POMB and 118 patients have completed therapy. The overall survival rate since 1979 is 89% and for the 100 patients who had not received prior radiotherapy it is 92%. We established that an initial serum concentration of human chorionic gonadotrophin (HCG greater than 50,000 iu/l) and/or alphafetoprotein (AFP greater than 500 ku/l) indicated a poor prognosis. Between 1977 and 1979 the survival rate in 12 patients in this category was only 45%. After increasing the number of courses of POMB, the survival rate rose to 89% in 31 patients. However, patients who had received prior radiotherapy and who presented with high tumour markers (HCG greater than 50,000 iu/l and/or AFP greater than 500 ku/l) continue to have a poor survival rate (20% in five patients). With this chemotherapy, 14 of 16 patients (88%) presenting with liver metastases and 6 of 7 patients (86%) presenting with brain metastases are in complete remission. Neither the stage at presentation nor the volume of metastatic disease was a major adverse prognostic variable. We believe that POMB/ACE chemotherapy, followed by surgery in selected cases, is currently the best treatment for patients with AGCT.

Antineoplastic Combined Chemotherapy Protocols↗

Developments in chemotherapy for medium- and high-risk patients with gestational trophoblastic tumours (1979-1984).

Identification of various prognostic factors at the start of chemotherapy allows patients with gestational trophoblastic tumours to be categorized into low-, medium- and high-risk groups so that they can be given the minimum treatment necessary to eliminate their disease. Most patients in the low-risk category can be treated with minimal toxicity using a methotrexate/folinic acid regimen and these patients are not considered in this report. Before 1979 patients in the medium-risk category were treated with a sequence of drugs which included, hydroxyurea, methotrexate, 6-mercaptopurine, actinomycin D, vincristine and cyclophosphamide. Since 1979 etoposide has been substituted for vincristine and cyclophosphamide. The 76 patients treated between 1979 and 1983 are all alive and in remission 1.1.85. Three patients (4%) relapsed and required retreatment and all are in remission. Fifty-six patients in the high-risk group, most at risk of developing drug resistance, were treated with a regimen incorporating etoposide with methotrexate, actinomycin D (EMA) and vincristine and cyclophosphamide (CO). EMA and CO were given on alternate weeks, resulting in an overall survival rate of 84%. Patients who had received prior chemotherapy had a survival rate of 74% and a relapse rate of 19% compared with 93% survival and 3% relapse rate in those who had not received prior chemotherapy. Toxicity with the EMA/CO regimen was significantly less than with an earlier regimen (CHAMOCA) used in the high-risk group.

Adult↗

Preparation and properties of mouse monoclonal antibody (W14A) to human chorionic gonadotropin.

A mouse monoclonal antibody, W14A, has been prepared which reacts with intact human chorionic gonadotropin and its beta-subunit, showing less than 2% cross-reactivity towards the alpha-subunit and 0.5% cross-reactivity towards the beta-subunit of luteinizing hormone. The reagent is suitable for the radioimmunolocalization of choriocarcinoma and trophoblastic teratoma in humans. A preliminary radioimmunoassay has been developed.

Animals↗