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Biomedical subjects

R H Begent

Publications and source records attributed to R H Begent.

At least 109 records · Page 6Linked to original sources
PubMed1989

EMOP/CA chemotherapy for the treatment of aggressive non-Hodgkin's lymphomas.

From October 1983 to June 1987, 32 patients with aggressive non-Hodgkin's lymphomas (diffuse centroblastic, lymphoblastic and Burkitt type) were treated with the weekly alternating EMOP/CA schedule, total duration 12 weeks. There were six bulky stage II, nine stage III and 17 stage IV patients, median age 54 years (range 19-75). The complete remission rate was 59% (95% confidence limits 40-76%) and the partial remission rate 28% providing an overall response rate of 87%. With a median follow up time of 33 months (range 18-56) the relapse-free survival of those patients achieving a complete remission is 52% and the overall survival for the 32 patients treated is 27%. The CR rate for patients with stage IV disease was 47% and for those with stage II and III disease was 73% of whom 81% remain in remission. EMOP/CA chemotherapy produces acceptable results in stage II and III aggressive non-Hodgkin's lymphomas but is inadequate therapy for stage IV disease.

Adult↗
PubMed1989

Antibody distribution and dosimetry in patients receiving radiolabelled antibody therapy for colorectal cancer.

The distribution of iodine-131 (131I) labelled antibody to carcinoembryonic antigen (CEA) has been studied in 16 patients with colorectal cancer. Levels of tumour and normal tissue radioactivity were measured by serial gamma-camera imaging and counting of blood and urine. Maximum concentrations were found in tumour 8 h after administration and varied up to 9-fold in different patients. Higher levels were found on average in tumour than in any other tissue. Liver, lung and blood were the other tissues in which antibody was concentrated relative to the rest of the body. Antibody cleared from all these tissues over 1 week. Second antibody directed against the antitumour (first) antibody was given 24 h after first antibody in order to accelerate clearance from the blood. This increased the tumour to blood ratio but had little effect on other tissues. Cumulative radiation dose to tumour and normal tissue was estimated. In patients with the most efficient localisation the tumour to body ratio was 20:1 and tumour to blood ratio 5:1. This may be sufficient for effective therapy of cancer in patients selected for efficient antibody localisation. The data may be used to estimate the effect of different therapeutic strategies. For instance, in the time after second antibody administration the average tumour to blood ratio of radiation dose was 11:1, suggesting that two phase systems in which the therapeutic modality is given after a good tumour to normal tissue ratio is obtained may be effective for the majority of patients.

Antibodies, Neoplasm↗
PubMed1989

Long-term outcome in patients with germ cell tumours treated with POMB/ACE chemotherapy: comparison of commonly used classification systems of good and poor prognosis.

We analysed outcome in 206 consecutive male patients treated for metastatic non-seminomatous germ cell tumour (NSGCT) of testicular or extragonadal origin treated with the POMB/ACE (cisplatin, vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide, etoposide) regimen after division into prognostic groups by commonly used clinical classification systems and definitions of adverse prognosis. The adverse prognostic groups of all classification systems and definitions examined showed similar, but only moderate, sensitivity (71-81%) and specificity (52-56%) in predicting death. A simple definition of poor prognosis based on raised initial levels of serum tumour markers alpha fetoprotein (aFP) and human chorionic gonadotrophin (hCG) proved at least as useful (sensitivity 80%, specificity 55%) as other more complicated systems in predicting failure to achieve long-term survival. Comparison of survival between ultra-high dose cisplatin-based combination chemotherapy and patients treated with POMB/ACE shows no advantage from this more toxic approach. This suggests that good results in adverse prognosis patients can be achieved using conventional dose regimens administered intensively.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

The effect of intensity of administered treatment on the outcome of germ cell tumours treated with POMB/ACE chemotherapy.

In order to assess the importance of the intensity of administration of chemotherapy in the management of advanced germ cell tumours we have calculated indices of chemotherapy. These have been used to compare the treatment given to patients who subsequently relapsed with matched controls who did not relapse. Two of these indices (alpha and beta) are derived from the doses of drugs whose dose is varied (cisplatinum, methotrexate and etoposide). These indices showed significant variation between cases and controls. Indices gamma and delta are derived from drugs whose dose is not varied. They showed no significant differences between the two groups. These results emphasise the importance of ensuring that patients with these curable cancers receive adequate doses of chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Lumbar pain in stage 1 testicular germ cell tumours: a symptom preceding radiological abnormality.

In a series of 114 stage 1 testicular tumour patients managed by a surveillance policy there have been 26 relapses. Three of these patients presented with lumbar pain as the first sign of relapse. All 3 were tumour marker non-producers and the onset of pain pre-dated radiological abnormality by up to 4 months. Stage 1 surveillance patients who develop lumbar pain must be considered to be at high risk of relapse to avoid delay in diagnosis which may prejudice survival.

Adult↗
PubMed1989

Doppler time velocity waveform studies of the uterine artery and uterus.

This study describes a reliable and reproducible method of obtaining Doppler frequency shift waveforms from the uterine artery based on observations in 26 non-pregnant women. The waveforms were detected easily but direct display of the vessel was inconsistent. The values of the pulsatility index calculated from the waveforms had a mean of 3.25 (SD 0.83). The standard error of the mean was 0.16 and based on this, the 95% reference range was 1.21 to 5.29. The stage of the menstrual cycle did not affect the pulsatility index nor was there any significant difference between subjects who were nulliparous and those who had had previous pregnancies. These results show that Doppler ultrasound can be applied to the non-pregnant uterus and the data presented may be used as a baseline for the study of uterine pathology.

Adult↗
PubMed1989

The role of low-dose methotrexate and folinic acid in gestational trophoblastic tumours (GTT).

Between 1964 and 1986, 487 patients with gestational trophoblastic tumour (GTT) were treated with methotrexate and folinic acid. The patients comprise two groups: between 1964 and 1974, 126 patients were treated but were not systematically stratified using a prognostic score before the start of treatment. These patients formed part of the 317 women who were analysed to identify a number of prognostic variables (Bagshawe 1976). Retrospective analysis of these 126 patients using these prognostic factors showed that in the true low-risk group 85/88 (96%) are alive while 20/22 (91%) of the medium-risk group and only 5/16 (31%) of the high-risk group are alive. Overall the survival was 110/126 (87%) with a minimum follow-up of 14 years. From 1974 all patients were stratified on admission into prognostic groups. Of the true low-risk patients 347/348 survived (99.7%); 13 patients were underscored and treated as low risk when they should have been treated as medium risk, 12 (92%) of these are alive, but nine (69%) needed to change treatment because of drug resistance. While the overall survival in the 1974-1986 group was 359/361 (99%) with a minimum follow-up of 16 months, the survival in all patients (1964-1986) was 469/487 (96%). Although the survival in these patients is excellent it should be noted that 69/348 (20%) low-risk patients had to change treatment because of the development of drug resistance, and a further 23 (6%) needed to change treatment because of drug-induced toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Weekly alternating etoposide, methotrexate, and actinomycin/vincristine and cyclophosphamide chemotherapy for the treatment of CNS metastases of choriocarcinoma.

Twenty-five patients with CNS metastases of choriocarcinoma were treated with a regimen incorporating etoposide, methotrexate, and actinomycin (EMA) alternating weekly with vincristine and cyclophosphamide (CO). The dose of methotrexate was increased to 1 g/m2. Eighteen patients presented with CNS metastases, or developed them on inappropriate treatment started elsewhere. Following EMA/CO chemotherapy, three patients died within the first 3 weeks, one is alive with active disease, one died with drug resistance, and 13 (72%) patients are surviving disease-free. Two of seven patients (29%) who developed CNS metastases on treatment with EMA/CO or relapsed after EMA/CO are disease-free after additional chemotherapy and surgery. The contribution toward survival of the craniotomy in six of 18 patients treated initially or early with EMA/CO remains unclear, but was crucial to those patients with drug resistance.

Adult↗
PubMed1989

Clinical value of imaging using antibody to alpha fetoprotein in germ cell tumours.

Germ cell tumours (GCT) producing alpha fetoprotein (aFP) can be imaged by external scintigraphy after intravenous administration of radiolabelled antibody directed against aFP. Antibody imaging (AI) by this method was used in an attempt to guide surgical resection of deposits of drug-resistant or recurrent GCT. 30 patients with GCT and raised aFP in whom site of tumour was not known were investigated by AI and conventional imaging methods. All but one were heavily pretreated. Where tumour appeared localised, resection was attempted. Tumour was found in all sites positive by both AI and conventional imaging. AI produced false-positive results in one of 30 patients and false-negative results in 9 patients. Computerised tomography was false-positive in one case and false-negative in three. In these patients, AI gave true-negative and true-positive results, respectively. Of 11 patients with positive AI in whom resection was attempted, 6 achieved sustained complete response with up to 5 years follow-up. We conclude AI and conventional imaging methods to be complementary in selection for surgery of patients with drug-resistant or recurrent GCT.

Adult↗
PubMed1988

Single agent etoposide in gestational trophoblastic tumours. Experience at Charing Cross Hospital 1978-1987.

Two hundred and two patients with gestational trophoblastic tumours (GTT) were treated using single agent etoposide. Patients were divided into low, medium and high risk groups using a prognostic index. Initial chemotherapy commenced with etoposide in 101 patients and 94 were accessible. Partial response (PR), defined by a log fall in serum human chorionic gonadotrophin (hCG) concentration within 1 week, occurred in 63 patients (67%) and was more common among low (5/8; 63%) and medium risk (47/64; 73%) than high risk patients (11/22; 50%) although these differences were not significant (P greater than 0.05). No patient showed a sustained rise in hCG level after etoposide and 91 (97%) showed some decrease. Ninety-one (97%) of these patients remain alive and well with median follow-up of 63 months but 29 (31%) required more intensive combination therapy. Of three deaths, two were due to progressive disease and drug resistance. Among 101 patients who had received previous chemotherapy when etoposide was first administered, response to etoposide was accessible in 39. Of these, PR occurred in 18 (46%) and only one patient progressed after etoposide. With a median follow-up of 35 months, survival in this group is 92% (36/39). All deaths were due to progressive disease and drug resistance. Single agent etoposide is very active in GTT but should be used in combination chemotherapy for patients presenting with adverse prognostic factors.

Adult↗
PubMed1988

Cyclosporin A prevents the anti-murine antibody response to a monoclonal anti-tumour antibody in rabbits.

Repeated therapy of cancer with mouse monoclonal antibodies frequently produces antibodies directed against the administered antibody. We have investigated the ability of cyclosporin A (CsA) and the use of ultracentrifuged antibody to prevent the formation of anti-antibodies in rabbits. Courses of CsA, 20 mgkg-1 day-1, were given intramuscularly for 6 days to rabbits and a mouse monoclonal anti-human chorionic gonadotrophin antibody was given intravenously on day 2 with or without ultracentrifugation to remove microaggregates. The whole course was repeated after an interval of two weeks. Rabbit anti-mouse antibody production was prevented in all 8 animals that were given CsA and ultracentrifuged preparation (non UC-W14). Anti-mouse antibody was produced by all the animals that were not given CsA. A further dose of mouse antibody eight weeks after CsA demonstrated that immunological recovery had occurred in all four animals re-challenged with non UC-W14 but only 3/7 animals given an UC-W14 preparation. This suggests that CsA and ultracentrifugation facilitate the induction of immunological tolerance. The complete suppression of antibody production which could be achieved justifies a clinical trial of CsA and ultracentrifugation of antibody.

Animals↗
PubMed1988

Repeated antitumour antibody therapy in man with suppression of the host response by cyclosporin A.

Antibody targeted therapy of cancer results in anti-antibody production which prevents repeated treatment. Cyclosporin A (CsA) has been used to suppress this response in patients treated with a radiolabelled antibody to carcinoembryonic antigen (CEA). Patients with CEA producing tumours received a minimum of two courses consisting of an injection of radiolabelled antibody and CsA, 24 mg kg-1 day-1, for 6 days; each course was given at 2 week intervals. Two weeks after the completion of the second course the mean human antimouse antibody (HAMA) levels were 3.5 micrograms ml-1 (s.d. 2.7) in 3 patients receiving CsA and 1,998 micrograms ml-1 (s.d. 387) in 3 patients not receiving the drug. Clearance of antitumour antibody was accelerated and tumour localisation absent when HAMA levels exceeded 30 micrograms ml-1. With lower levels of HAMA in the CsA-treated patients, further antitumour antibody accumulated in the tumour after each dose. Further therapy with antitumour antibody and CsA lead to the development of HAMA, but this was less than 25% of the amount in patients not given CsA. In this preliminary study up to 4 times as many doses of antitumour antibody could be usefully given when CsA was used. This increases the potential for effective antibody targeted therapy of cancer.

Adult↗
PubMed1988

Bone disease in testicular and extragonadal germ cell tumours.

Of 297 patients with metastatic testicular and extragonadal germ cell tumours (GCT), bone involvement was detected clinically in 3% (7/251) of those at first presentation and in 9% (4/46) of relapsed cases. This difference was not statistically significant (95% confidence limits -2%; +14%). Concurrent systemic metastases, commonly involving lung (7/11 cases) and para-aortic lymph nodes (6/11), were present in all patients with bone disease. All affected patients had localized bone pain and lumbar spine was the most frequent site involved (9/11). Spinal cord compression occurred in two patients while a third developed progressive vertebral collapse after chemotherapy and required extensive surgical reconstruction. At median follow-up of 4 years, survival among patients presenting with bone disease (6/7) was similar to overall survival in the whole group (84%) and appeared better than in those with liver (18/26, 69%) or central nervous system (6/9) metastases at presentation. Back pain in metastatic germ cell tumours is often due to retroperitoneal lymphadenopathy but lumbar spine osseus metastases must be recognized early if severe potential complications, such as spinal cord compression, are to be avoided. In this series, bone metastases were not seen in the absence of widespread systemic disease suggesting all solitary bony lesions in GCT patients should be biopsied.

Adolescent↗
PubMed1988

Safety of surveillance in the management of stage I anaplastic germ cell tumours of the testis.

A study was made of 46 patients with anaplastic germ cell tumours of the testis with no evidence of disease elsewhere as judged by computed tomography (CT) of thorax and abdomen, ultrasound and tumour marker measurements. A repeat CT 3 months after the first and clinical examination with chest X-ray and tumour marker measurements ensured that the 30.7% of patients who relapsed were detected promptly enough for them all to enter complete remission. Lymphography as part of the staging did not reduce the relapse rate. There was no difference between this group and a comparable group who underwent radiotherapy to para-aortic lymph nodes.

Biomarkers, Tumor↗
PubMed1988

Quantitation in 131I-radioimmunotherapy using SPECT.

Quantitation from planar imaging and single photon emission computed tomography (SPECT) were compared in phantom studies and in patients receiving therapeutic doses of 131I-labelled anti-CEA. During the reconstruction of the data for SPECT quantitation attenuation correction and a correction for Compton scatter were used. The limitations of both methods were examined using the phantom studies and it was shown that practical SPECT quantitation could be achieved in patients given therapeutic doses of 131I-labelled anti-CEA, and furthermore, that SPECT appeared to give a more accurate estimate of the activity concentration.

Carcinoembryonic Antigen↗
PubMed1987

Surgery, chemotherapy and whole abdominal radiotherapy in the management of advanced ovarian carcinoma.

A pilot study on 35 women was performed to determine the feasibility of giving whole abdominal radiotherapy after surgery and chemotherapy for Stage III and IV ovarian adenocarcinoma. The planned duration of therapy was only 6 months from diagnosis. Chemotherapy consisted of four courses of cis-platinum 100 mg/m2 alternating every 10-12 days with four courses of methotrexate 300 mg/m2 and cyclophosphamide 500 mg/m2 followed by folinic acid rescue. Twenty-nine of 35 (83%) patients were shown at second look surgery after chemotherapy to have residual tumour deposits no more than 2 cm in diameter. The usual radiotherapy dose was 2400 cGy in 20 fractions over approximately 4 to 5 weeks, with kidney shielding, and was generally well tolerated. Three patients failed to complete radiotherapy, two because of progressive disease and one because of persistent nausea and vomiting. During radiotherapy the white blood count fell below 2.0 X 10(9)/litre in seven patients (26%), and in eight patients (30%) the platelet count fell below 75 X 10(9)/litre. However, the white blood count nadir of 1.5 X 10(9)/litre was reached by 1300 cGy and the platelet nadir of 45 X 10(9)/litre was reached by 1400 cGy and both then levelled or recovered despite continuing radiotherapy. The median follow up since diagnosis is 26 months. Four of 12 patients with no tumour detected at second look operation have relapsed compared with 13 of 15 patients who had detectable tumour. Toxicity of this multi-modality therapy was acceptable.

Abdomen↗