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K D Bagshawe

Publications and source records attributed to K D Bagshawe.

At least 91 records · Page 5Linked to original sources
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

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

Use of CA-125 to predict survival of patients with ovarian carcinoma. North Thames Cooperative Group.

The prognostic value of serum CA-125 measurements was assessed in 54 patients with advanced ovarian adenocarcinoma. All patients received a minimum of two courses of carboplatin as part of the North Thames Cooperative Group trial. With a minimum follow-up of 6 months, 37 patients (69%) have clinical evidence of progressive disease and 28 have died. The absolute prechemotherapy level of CA-125 was of no value in predicting which patients would develop progressive disease. However, the change in CA-125 levels from before chemotherapy to 1 month later, after one course of carboplatin, could be used to divide patients into different prognostic groups. The best discrimination was found by dividing the patients into those who showed a greater than sevenfold decrease in CA-125 levels and those who showed a smaller change. Eight of 14 (58%) patients with a greater than sevenfold decrease in CA-125 levels remain disease-free compared with three of 36 (9%) patients with a lesser fall (P = .0005). The change in CA-125 levels during the first month of chemotherapy may indicate which patients should be offered alternative or symptomatic therapy and which should continue with the currently available toxic chemotherapy.

Antibodies, Monoclonal↗
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

Second antibody for improvement of antibody imaging: liposome-entrapped and free preparations in animal and human studies.

When anti-tumour antibodies are given systematically for tumour imaging or therapy, second antibody directed against the first (anti-tumour) antibody can be used to accelerate clearance of first antibody, thus improving discrimination between tumour and normal tissues. Liposome-entrapped, and free second antibodies (LESA and FSA, respectively) have been compared in an animal tumour model system and in patients with cancer. Nude mice bearing xenografts of human colon carcinoma were given goat antibody to carcino-embryonic antigen (CEA) as first antibody and horse anti-goat second antibody. Patients with gastrointestinal carcinomas received i.v. 131I-labelled goat anti-CEA or mouse monoclonal 17-1A first antibody and unlabelled horse angi-goat or rabbit anti-mouse second antibody, respectively. Antibody distribution was studied by serial gamma camera imaging. The effectiveness of LESA and FSA depended on dose. Tumour-to-blood ratios were increased up to eight-fold by either method in animals. Tumour imaging was enhanced among 15 patients with gastrointestinal cancer and tumour was correctly identified at five sites where it was not seen by a background subtraction method. No significant toxicity occurred in patients nor in rabbits studied for evidence of immune complex mediated disease. LESA and FSA appear to be equally effective.

Animals↗
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 activity of methotrexate in advanced non-seminomatous testicular germ cell tumours.

The single agent activity of methotrexate in non-seminomatous germ cell tumours (NSGCT), and thus the rationale for its inclusion in combination regimens, has never been documented clearly. We have therefore reviewed all patients with NSGCT treated in this hospital from 1967 to 1970. Seventeen patients were identified who had a rising HCG excretion and who were treated with methotrexate alone as first line chemotherapy. Nine patients (53%) obtained a partial remission and a further seven patients a reduction in HCG production that was less than one log. Methotrexate is an active agent in testicular germ cell tumours and should be of particular value in treating CNS disease where intrathecal treatment may be required.

Adolescent↗
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

Urinary gonadotrophin peptide--isolation and purification, and its immunohistochemical distribution in normal and neoplastic tissues.

A urinary gonadotrophin peptide (UGP) was isolated and purified from semi-purified human chorionic gonadotrophin (hCG), prepared from pregnancy urine. The peptide showed hCG-B subunit activity and no hCG-alpha subunit activity as demonstrated by binding studies with the relevant antibodies. It had a molecular weight significantly less than hCG-B subunit. The peptide was linked to thyroglobulin and this conjugate used to immunise rabbits and mice. A radioimmunoassay (RIA) using 125I-UGP and the rabbit antiserum (AK12) was used to monitor chromatographed urine fractions from patients with ovarian carcinoma, seminoma and hydatidiform mole. UGP was also found in the urine extract of a healthy male, but at a much lower level. In each case the UGP detected had the same molecular weight as the pregnancy preparation and appeared to be the main gonadotrophin constituent in those urine samples. Initial immunohistochemical screening of normal and neoplastic tissues with the rabbit antibody (AK12) showed reactivity with some tumours including carcinomas of the lung, ovary, cervix and breast as well as trophoblastic and germ cell tumours. Reactions with non-neoplastic tissues were confined to some specialised epithelia and macrophage populations. A more comprehensive immunohistochemical study was made using a monoclonal antibody to UGP (2C2), with a monoclonal antibody to conformational hCG (INN 13) and another monoclonal antibody to free B subunit (1E5) as controls. Similar patterns of reactivity were produced by the AK12 and 2C2 antibodies in both neoplastic and non-neoplastic tissues. Additional tissues were investigated with the three monoclonal antibodies. The 2C2 antibody reacted with 93% (77/83) of tumours examined; the INN 13 antibody reacted with only the syncytiotrophoblast cells of choriocarcinoma, hydatidiform mole, placental site trophoblastic tumour, and in one case of seminoma; the 1E5 reactivity was confined to only choriocarcinoma syncytiotrophoblast cells.

Chorionic Gonadotropin↗
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

A cytotoxic agent can be generated selectively at cancer sites.

Attempts to improve the selectivity of anti-cancer agents by conjugating them to antibodies directed at tumour associated antigens have demonstrated tumour localisation but only limited therapeutic success. We report here the advantage of a 2-stage approach in which the first component combines the selective delivery of antibody with a capability to generate a cytotoxic agent from a second subsequently administered component. A bacterial enzyme, carboxypeptidase G2 (CPG2) was conjugated with F(ab')2 fragment of a monoclonal antibody directed at beta subunit of human chorionic gonadotrophin (beta-hCG) and injected into nude mice bearing hCG producing CC3 xenografts of human choriocarcinoma. Time was allowed for the conjugate to localise at tumour sites and clear from blood before injecting para-N-bis (2-chloroethyl) aminobenzoylglutamic acid. Cleavage of the glutamic acid moiety from this molecule by CPG2 released a benzoic acid mustard. Growth of the tumour which is resistant to conventional chemotherapy was markedly depressed by a single course of treatment. This demonstrates for the first time the potential of an antibody directed enzyme to activate an alkylating agent and to eradicate an established human cancer xenograft.

4-Aminobenzoic Acid↗
PubMed1988

Genetically homozygous choriocarcinoma following pregnancy with hydatidiform mole.

Genetic studies have been made in two cases of primary choriocarcinoma from patients in whom the antecedent pregnancy was a hydatidiform mole. Restriction fragment length polymorphisms of the DNA from the tumour, the patient and her partner were examined and in both cases the tumours were shown to be androgenetic in origin, having only paternal polymorphisms. While one tumour was shown to be heterozygous, two different paternal alleles being demonstrated with some probes, the other tumour was shown to be homozygous for all informative polymorphisms examined. Thus choriocarcinoma can follow complete hydatidiform mole which may be either heterozygous or homozygous.

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↗