Search PubMed⌕ Search

Biomedical subjects

G Blackledge

Publications and source records attributed to G Blackledge.

At least 73 records · Page 4Linked to original sources
PubMed1986

Pharmacokinetic and endocrinological parameters of a slow-release depot preparation of the GnRH analogue ICI 118630 (zoladex) compared with a subcutaneous bolus and continuous subcutaneous infusion of the same drug in patients with prostatic cancer.

Seventeen patients with advanced prostatic cancer were treated with the gonadotrophin-releasing hormone analogue DSer (tBU)6 AzaGly 10 GnRH (ICI 118630), either as a constant SC infusion, or in the form of a monthly SC slowrelease depot formulation, in which case patients were randomised to receive one of three doses. Six of these patients also received a 250-microgram SC bolus of ICI 118630, for pharmacokinetic studies, before starting the infusion or the depot. Drug levels were measured using a double-antibody radioimmunoassay. In contrast to the SC infusion, which gave a smooth serum 118630 level profile, drug release from the depot preparation was not constant, levels varying in a predictable manner throughout each 28-day period, reaching a peak proportional to the dose of ICI 118630 received, between days 15 and 18 of each cycle. With all methods of administration there was an initial rise in LH, usually followed by a rise in testosterone, after which the SC infusion and the depot were both effective in reducing serum LH to basal levels and testosterone into the castrate range within 1 month. It is too early to make any assessment of clinical response; however, depot treatment was well tolerated: Four patients experienced an initial flare in bone pain, probably related to the initial rise in testosterone, and twelve patients experienced flushing; one patient with pre-existing hydronephrosis and hydroureter developed renal failure, possibly related to a tumour flare reaction. No patients have experienced cardiovascular side effects or local reaction.

Buserelin↗
PubMed1986

Cyclophosphamide versus ifosfamide: preliminary report of a randomized phase II trial in adult soft tissue sarcomas.

One hundred and seventy-one patients with advanced soft tissue sarcoma entered a randomized crossover phase II study comparing cyclophosphamide (CYCLO) with a new analogue, ifosfamide (IFOS), both administered as 24 h i.v. infusions every 3 weeks. The doses used were CYCLO 1.5 g/m2 and IFOS 5 g/m2, with provision for dose escalation. All patients received mesna 400 mg/m2 as an i.v. bolus 4 hourly X 9 doses, commencing at the start of the oxazophosphorine infusion. Patients who had received previous chemotherapy were eligible provided this did not include a classical alkylating agent. There were 22 patients who were ineligible, and response could not be evaluated in 12 additional patients. IFOS produced two complete and ten partial remissions, for an overall response rate of 18%. CYCLO was significantly (P = 0.04) less active, producing one complete and five partial remissions, an overall response rate of 9%. Stabilization of disease was similar in both arms (27% and 24% respectively), but fewer patients showed progression on IFOS. The response rate was higher (20% vs 5%) for patients who had not received previous chemotherapy, and also for female compared with male patients (21% vs 5%). When only patients who had not received previous chemotherapy were considered, the respective response rates for IFOS and CYCLO were 24% and 15%. There were no responses in previously treated patients receiving CYCLO. There were four partial responses in 33 patients crossing from CYCLO to IFOS, but no responses in 18 patients receiving CYCLO after IFOS. Leucopenia was significantly more pronounced (P = 0.0004) with CYCLO, both after the first course and throughout treatment, although the incidence of severe infections, 6%, was the same in both arms. Nausea and vomiting were more severe with IFOS (P = 0.022), but other toxicities were mild. Grade 1 or 2 bladder (haematuria) or renal (rise in serum creatinine) toxicity was slightly more frequent with IFOS (7 vs 3 patients) and was a reason for stopping treatment for one patient in each arm. Three episodes of mild to moderate drowsiness after IFOS were reported, but no severe encephalopathy. A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination with such active agents as adriamycin.

Adolescent↗
PubMed1986

Prediction of ifosfamide/mesna associated encephalopathy.

Ifosfamide and mesna were administered to 77 patients with advanced malignancies. Seven (9%) experienced a severe but reversible encephalopathy. In 56% of patients in whom EEG data was available, characteristic changes were seen with or without mild clinical toxicity. Discriminant analysis identified low serum albumin concentration, high serum creatinine concentration and the presence of pelvic disease as variables which predispose patients to the development of severe encephalopathy. A nomogram has been constructed which can be used to determine the probability that an individual patient may be given ifosfamide and mesna safely. This has important implications for the clinical use of a highly active chemotherapy regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Phase II study of ifosfamide in cervical cancer.

Thirty patients with symptomatic, progressive squamous cell carcinoma of the uterine cervix no longer amenable to surgery or radiotherapy were entered in a phase II study of ifosfamide (IFX). Patients were treated with IFX (5 g/m2 iv given over 24 hours) and concomitant mesna (total dose, 9.2 g/m2 iv given over 36 hours) every 21 days. One complete response (duration, 10+ months) and nine partial responses were observed, with an overall median response duration of 6.5 months. The median survival of responding patients was 11 months. Objective response rates for lesions arising in previously irradiated sites (four of 22) were significantly lower than for lesions arising in nonirradiated sites (15 of 28) (P = 0.018). There were two treatment-related deaths: one due to leukopenia-associated infection in a patient with peritonitis and severe central nervous system toxicity and one due to central nervous system toxicity without complicating factors. One other patient developed severe but reversible encephalopathy. In all remaining patients hemorrhagic cystitis and hematological and gastrointestinal toxic effects were predictable and manageable. Treatment was delayed for 1 week due to toxicity on seven of 101 occasions: four of these delays were due to mild, reversible impairment of renal function and three were due to leukopenia. Complete though reversible alopecia occurred in 22 of 30 patients. The results indicate that IFX is active in cervical cancer and deserves further study in this setting.

Adult↗
PubMed1985

Phase II study of vincristine, mitomycin-C and mitoxantrone in advanced breast cancer: a preliminary report of response and toxicity.

Nineteen patients with advanced, previously treated breast cancer received treatment with vincristine 2 mg i.v., mitomycin-C 6 mg/m2 and mitoxantrone (Novantrone; dihydroxyanthracenedione) 12 mg/m2 i.v. every three weeks. Thirteen patients are evaluable for response and toxicity. Partial remission was seen in six patients, with soft tissue, bone and visceral metastases and static disease in a further four patients. Median duration of response has not yet been reached (8+ months). Toxicity was mild and predictable, with no patient experiencing severe nausea and vomiting, and only four of the patients requiring a wig for alopecia. Malaise and lethargy were common in those patients receiving more than three courses, and an increase in the mean corpuscular volume (MCV) together with a fall in haemoglobin were seen in patients receiving multiple courses of treatment. The study suggests that this combination is active, and may prove useful with other agents in the treatment of breast cancer.

Adolescent↗
PubMed1985

Sequential chemotherapy for advanced epithelial ovarian cancer: platinum combination cytoreduction followed by cyclophosphamide consolidation.

Thirty-six women with advanced epithelial ovarian cancer were treated with a combination of cisplatin, vinblastine and bleomycin followed by a consolidation regimen of intravenous cyclophosphamide. There was a 53% response rate in previously untreated patients with 25% complete clinical remissions. Sixteen per cent of previously untreated patients remain in a complete clinical remission of greater than 3 yr duration. In a multivariate analysis bulk tumor residuum was not a significant adverse factor in terms of survival, suggesting that intensive chemical cytoreduction followed by non-cross-resistant consolidation may overcome such prognostic variables.

Adult↗
PubMed1985

Assessment of bleomycin, adriamycin and mitomycin-C in the treatment of recurrent cervical cancer.

Twenty women with recurrent squamous cell carcinoma of the cervix were treated with bleomycin followed by adriamycin and mitomycin-C. Treatment was repeated every 28 days. In 18 patients who could be assessed there was one complete response and five partial responses (response rate 33%). Two partial responses were seen in 13 lesions arising from previously irradiated sites of disease (response rate 23%). Three complete responses and three partial responses were observed in 10 lesions arising from non-previously irradiated sites of disease (response rate 60%). In all responding cases tumour regression was noted before the end of the third cycle of treatment. Toxicity was predictable and manageable. These results suggest that chemotherapy may be used as a cytoreductive procedure before radical local treatment.

Adult↗
PubMed1984

A multivariate analysis of factors affecting survival in patients with high-grade histology non-Hodgkin's lymphoma.

One hundred and eleven patients with advanced-stage, high-grade histology non-Hodgkin's lymphoma were studied over a 7-yr period and were treated with one form of chemotherapy and radiotherapy. Multivariate analyses were carried out to identify factors which could predict a favourable prognosis. A complete response, low serum LDH and absence of clinical evidence of liver involvement were associated with long-term survival. The presence of 'B' symptoms, bone marrow involvement, low serum albumin and male sex predicted a reduced chance of achieving a complete remission. For those patients who achieved a complete response, the subdivision of histologies, particularly according to the Kiel classification, was the only significant factor predictive of prolonged relapse-free and overall survival. This confirms the importance of identifying different histological subgroups of lymphoma when considering treatment planning.

Aged↗
PubMed1984

A randomised study of adjuvant chemotherapy after mantle radiotherapy in supradiaphragmatic Hodgkin's disease PS IA-IIB: a report from the Manchester lymphoma group.

One hundred and fourteen untreated patients with pathological stage (PS) IA-IIB supradiaphragmatic Hodgkin's Disease were randomised to mantle radiotherapy alone (55) or mantle radiotherapy followed by 6 courses of adjuvant chemotherapy with mustine, vinblastine, prednisolone and procarbazine- MVPP (59). Patients excluded were those outside the age range 16-65 years and those with massive mediastinal disease precluding laparotomy. Bulk disease was defined as a mass of lymph nodes measuring five centimetres or more in any axis. Mediastinal bulk was present if the ratio of the maximum width of mediastinal disease to the maximal chest diameter was more than one third. All patients achieved a complete remission. Median duration of follow-up was 62 months (range 16-97). The relapse free survival (RFS) was 81%; 69% for radiotherapy alone and 93% for adjuvant chemotherapy (P = 0.002). RFS was also shown to be adversely affected by B symptoms (P = 0.0003), bulk disease (P = 0.018), abnormal CXR (P = 0.037), and increasing stage (P = 0.039). Age, sex, histology, and number of sites involved had no significant effect upon RFS. A Cox multivariate analysis showed that only three variables had a significant adverse effect on RFS - radiotherapy alone, the presence of bulk disease, and B symptoms. The overall 5 year survival was 93% with no statistically significant difference between the two treatment groups (P = 0.54). Survival was adversely affected by three variables - B symptoms (P = 0.02), the presence of bulk disease (P = 0.002), and pathological stage (P = 0.05). High risk groups for relapse are those with bulk and B symptoms. This analysis has shown that RFS was significantly improved by adjuvant chemotherapy, but that overall survival was not.

Adolescent↗
PubMed1984

A randomized study comparing chemotherapy alone with chemotherapy followed by radiotherapy in patients with pathologically staged IIIA Hodgkin's disease.

This paper reports the five-year follow-up (range, 1-8 years) of 56 patients with pathologic stage IIIA Hodgkin's disease randomized for chemotherapy alone or chemotherapy followed by radiotherapy to previous areas of disease (26 treated with mustine, vinblastine, procarbazine, and prednisolone [MVPP] alone, 30 with MVPP and radiotherapy). Of the 56 patients 53 (95%) achieved a complete remission with chemotherapy and of these only five (9%) have relapsed; three died of Hodgkin's disease. There was no improvement in relapse-free survival associated with the uses of radiotherapy following chemotherapy but in view of the small numbers of relapses and the excellent results following chemotherapy alone, a significant improvement could not be expected. The use of MVPP alone can be recommended as an alternative therapy for patients with stage IIIA Hodgkin's disease. This avoids both the physical and psychologic morbidity associated with the high relapse rate following extensive primary radiotherapy and the necessity of combined modality treatment for about half these patients. The question of whether radiotherapy should be given to areas of previous bulk following chemotherapy has not yet been answered in this trial which is continuing.

Adult↗
PubMed1984

Phase II evaluation of bleomycin in patients with advanced epithelial ovarian cancer.

Twenty-four patients received bleomycin twice weekly im. Treatment was given for 3 weeks initially, and if there was no evidence of disease progression treatment was given for another 3 weeks. Four patients had partial responses of 2, 4, 4, and 5 months' duration. Three patients had stable disease which did not progress for at least 4 months. There were ten patients with ascites; three of these showed a significant reduction in the amount of ascites present during treatment. There was a partial reduction of tumor in one of these patients. Toxicity was minimal with this regimen, and bleomycin deserves further study in the treatment of ovarian cancer.

Adenocarcinoma↗
PubMed1983

The effect of combination chemotherapy on ovarian function in women treated for Hodgkin's disease.

Ovarian function has been studied in 44 adult females who previously received quadruple chemotherapy (MVPP) for Hodgkin's disease. The median age at treatment was 23 years, and the length of time between completion of treatment and study ranged from 6 months to 10 years (median, 30 months). Seventeen women maintained regular menses, 10 developed oligomenorrhea, and 17 developed amenorrhea. At treatment, the 17 women who subsequently developed amenorrhea were significantly older (median, 30 years) than those who maintained regular menses (median, 22 years) or developed oligomenorrhea (median, 23 years). All patients older than 36 years at the start of treatment stopped menstruating during chemotherapy. The cause of the menstrual disturbance in these patients was chemotherapy-induced ovarian damage characterized by high serum gonadotrophin and low serum estradiol concentrations. After completion of treatment there were 17 pregnancies, which resulted in 9 normal infants, 3 terminations, and 4 spontaneous abortions. Nine patients took the combination oral contraceptive pill throughout chemotherapy; however, subsequently 4 developed amenorrhea and 3 oligomenorrhea, suggesting that these patients had not been protected from chemotherapy-induced ovarian damage. Estrogen replacement therapy was of definite benefit in the symptomatic patients with premature ovarian failure.

Adolescent↗