Biomedical subjects

G R Blackledge

Publications and source records attributed to G R Blackledge.

46 records · Page 3Linked to original sources

PubMed1988

Interim report of a randomized trial comparing Zoladex 3.6 mg depot with diethylstilbestrol 3 mg/day in advanced prostate cancer. The West Midlands Urology Research Group.

A study comparing Zoladex 3.6 mg depot with diethylstilbestrol (DES) 3 mg/day was initiated in August 1985. One hundred ninety-three patients with histologically confirmed prostate cancer T3/4 or M1 have been randomized up to 31 March 1987: 95 to Zoladex, 98 to DES. No patient had received prior systemic therapy. There is no bias in the treatment groups in terms of baseline characteristics. Median follow-up is 11 months, and the response rate at 12 months from randomization (CR + PR) for Zoladex is 70 +/- 9.4% and 50 +/- 10.1% for DES. Median time to best response is 6 months for Zoladex and 12 months for DES (using the Kaplan-Meier life table method). Subjective responses are 56 +/- 10.2% for Zoladex and 44 +/- 10% for DES. Five increases in bone pain were found after the first Zoladex treatment, as well as one increased ureteric obstruction. None required treatment withdrawal. Seventeen patients on DES were withdrawn due to adverse reaction (chi 2 = 4.33, 1df, p less than 0.05). Overall survival at 31 March 1987 is 84% for the Zoladex group and 78% for the DES group. This study has shown that Zoladex is superior to DES in achieving early tumor response in advanced prostate cancer, without causing serious complications warranting withdrawal of treatment.

Buserelin↗

PubMed1988

Survival following intestinal obstruction in ovarian cancer.

A retrospective survey of 38 ovarian cancer patients who developed radiologically confirmed intestinal obstruction was performed. Twenty-six patients underwent surgery. In the surgical treatment group, obstruction was not due to recurrent disease in six cases. The median survival for the group as a whole was 56 days. Patients in the operative group survived significantly longer than those in the non-operative group. There was an operative mortality of 15% and major postoperative morbidity was seen in 42%. Neither the site of the obstruction nor the type of operation influenced survival. No postoperative chemotherapy responses were seen in previously treated patients.

Adult↗

PubMed1987

Phase II study of Zoladex depot in advanced prostatic cancer with special reference to criteria of response and survival.

Zoladex is a potent decapeptide analogue of luteinising hormone releasing hormone (LHRH). The drug is formulated as a 3.6 mg depot dispersed in a matrix of d,l-lactide-glycolide copolymer, which is totally biodegradable. This formula releases drug continuously for at least 28 days and reliably suppresses serum testosterone into the castrate range. The effect of the depot was studied in 29 patients with locally advanced or metastatic carcinoma of the prostate. Average age at entry was 71 years (range 52-87) and follow-up was from 13.5 to 34.5 months (median 23). Endocrine studies showed that medical castration was maintained in all cases. Three patients experienced bone pain in the first month of treatment and two others had temporary nephrostomies for worsening ureteric obstruction. Subjective improvement was seen in 23/28 cases (82%). There were no complete responses, but partial response was seen in 24/28 (85.7%) using our own criteria, 24/28 (85.7%) using the criteria recommended by the British Prostate Group (BPG) and 15/28 (53.6%) using NPCP criteria. Stable disease was seen in 3/28 patients (10.7%) by our own or BPG criteria, and in 12/28 patients (42.9%) according to NPCP criteria. Progression of disease was measurable in 21 patients (72.4%) whatever criteria were applied; 11/29 (37.9%) have died, giving a median survival of 10 months (range 2.4-26). Following these encouraging results, a multicentre randomised comparative study with stilboestrol 3 mg daily is being undertaken.

Aged↗

PubMed1987

The role of prostate specific antigen in the baseline assessment of patients undergoing hormone therapy for advanced prostate cancer.

One hundred and thirty-nine patients with advanced prostate cancer were entered into a randomised trial to test the efficacy and tolerance of goserelin 3.6 mg depot (Zoladex) versus stilboestrol 3 mg/day. As well as the usual clinical and radiological assessments of extent of disease, we used an immunoradiometric assay of prostate specific antigen (PSA) (Hybritech Europe) and normal laboratory enzymatic assays of acid phosphatase (AP) and alkaline phosphatase (ALKP) for biochemical assessment. The upper limit of normal for PSA was taken as 10 micrograms/l. The range of PSA was wide and differed significantly from that of AP and to a lesser extent ALKP in metastatic cases. PSA outperformed both AP and ALKP in both the local and advanced groups in terms of sensitivity. There was no correlation, however, between histological grade and level of PSA, AP or ALKP (the latter in cases with bone disease). In patients with metastatic disease diagnosed by bone scan, nine patients had one abnormal site/one "hot spot", and all of these had a PSA greater than twice the normal upper limit. Early death due to prostate cancer was noted in four patients with levels of PSA greater than 2500 micrograms/l. PSA is more sensitive than either enzymatic AP or ALKP in both locally advanced and metastatic prostate cancer and is useful in identifying those advanced cases who have single lesions on bone scan. In this series PSA gave an overall sensitivity of 89%, compared with 63% for AP and 64% for ALKP in patients with metastatic disease.

Acid Phosphatase↗

PubMed1987

Serial urinary cyclic guanosine monophosphate measurements in the assessment of response to treatment in epithelial ovarian cancer.

Serial measurements of urinary cyclic guanosine monophosphate (cGMP) were performed in 47 patients with epithelial ovarian cancer. In 30 patients, the pre-chemotherapy cGMP level was above the range for normal controls (marker positive); the remainder were within the normal range. Marker positive patients demonstrated a 96% correlation of disease regression with a fall in marker level and a 75% correlation of disease progression with a rise in marker level. The corresponding correlations in the marker negative group were 41% and 39%. Marker positive patients also demonstrated a rise in marker before clinical recognition of disease progression in six of 11 instances whereas only one of nine instances in marker negative patients showed such a rise. Patients with evidence of static disease had normal and stable marker levels.

Chlorambucil↗

PubMed1986

Phase II evaluation of megestrol acetate in previously treated patients with advanced breast cancer: relationship of response to previous treatment.

Thirty-seven patients with advanced breast cancer were treated with megestrol acetate 160 mg daily. All patients except two had been heavily pre-treated with hormonal therapy; eight patients also received chemotherapy. Complete and partial responses occurred in 25% with a mean duration of 5 months (range 2-24 months). A further 38% of patients had static disease for 2 months or greater. Seven patients had previously received medroxyprogesterone acetate, and responses were seen even in patients who had failed to respond to this therapy. This was thought to be due to the higher levels of progestogenic activity which can be routinely achieved with megestrol acetate. Toxicity was minimal, and we would therefore consider that megestrol acetate should be the progestogen of choice in advanced breast cancer.

Adult↗

PubMed1986

Random urinary cyclic 3',5' guanosine monophosphate in epithelial ovarian cancer: relation to other prognostic variables and to survival.

Random urinary cyclic guanosine monophosphate (cyclic GMP) has been measured in a control group of 83 women and in 92 women with histologically proven epithelial ovarian cancer. Forty-eight cancer patients (53%) had levels greater than the mean +2SD of the control population. There was no correlation between urinary cyclic GMP and tumour histology, degree of differentiation or stage. Patients with gross residual disease after laparotomy had higher postoperative levels. This degree of sensitivity in addition to poor specificity for ovarian cancer renders this marker unsuitable for screening purposes. While residual disease state after surgery was found to be the best single predictor of survival, an elevated urinary cyclic GMP level before chemotherapy was found to be an independent adverse prognostic variable.

Adolescent↗

PubMed1986

Haemorrhage and perforation of gastrointestinal neoplasms during chemotherapy.

Gastrointestinal haemorrhage and perforation are known complications of cytotoxic therapy for chemosensitive tumours involving the wall of the gut, in particular non-Hodgkin's lymphoma. These complications can be avoided by aggressive surgery before chemotherapy is started. When they do occur, early operative intervention is essential to reduce morbidity and mortality. We report 4 cases in whom delay in diagnosis and surgery led to 3 deaths and suggest a policy for the management of such cases in the future.

Adult↗

PubMed1985

A radioimmunoassay for GnRH agonist analogue in serum of patients with prostate cancer treated with D-Ser (tBu)6 AZA Gly10 GnRH.

A radioimmunoassay is described for D-Ser (tBu)6 AZA Gly10 GnRH (ICI 118630) in serum of prostate cancer patients treated chronically with this peptide to produce a medical castration. With 125I-118630 as the label, and an anti-GnRH serum, the specificity of the assay is directed to the N-terminal end of the peptide, and putative degradation products have less than 6% cross-reactivity. The assay appears specific for intact 118630 which, after subcutaneous administration of 250 micrograms, has a half-time of disappearance from the serum of 4.9 +/- 0.4 h and a volume of distribution of 13.7 +/- 0.8 litres. Continuous subcutaneous infusion of 120 micrograms 118630/d gave stable serum concentrations of between 2-3 ng/ml for up to 63 d which were very similar to values predicted from pharmacokinetic analysis of the analogue clearance rate. This contrasts with the "peak and trough' pattern of serum 118630 levels measured in two subjects after 118630 administration from a subcutaneous implant containing 3.6 mg of peptide in a biodegradable formulation. Serum 118630 levels peaked at between 6-8 ng/ml 15 d after the implant and fell to less than 1 ng/ml at 29 d, immediately before the next implant. Serum 118630 levels following a second 3.6 mg implant were almost identical with respect to absolute concentration and time to peak value as after the first implant. This assay will be of value not only for evaluation of the pharmacokinetics of GnRH analogue release from new long-acting formulations, but also for correlation of serum peptide concentrations with pituitary gonadotroph desensitization.

Buserelin↗

PubMed1984

Second-look laparotomy in the management of epithelial ovarian carcinoma: an evaluation of fifty cases.

Fifty patients with ovarian cancer had a second-look laparotomy performed after chemotherapy. Complete histologic response was confirmed in 12 patients, microscopic disease was found in 12 patients, and macroscopic disease was found in 26 patients. Fifteen patients with macroscopic disease had total tumor clearance at second look. Surgical response to chemotherapy was found to correlate well with disease volume at the onset of chemotherapy. The operation is a safe, accurate technique for assessing the ovarian cancer patient. The findings and outcome probably depend upon the timing of the procedure. Any survival benefit from the operation remains to be proved.

Adult↗