Response of carcinoma of the prostate to withdrawal of flutamide.
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Biomedical subjects
Publications and source records attributed to C J Tyrrell.
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Trilostane and Aminoglutethimide, each given with a physiological replacement dose of hydrocortisone, were randomly allocated to 72 eligible postmenopausal advanced breast cancer patients; following treatment failure on either drug the patient continued with the other drug, if in a suitable clinical condition. Thirty-eight patients initially received Trilostane of whom 19 subsequently received Aminoglutethimide; 34 patients initially had Aminoglutethimide and seven of these then received Trilostane. Both groups of patients were comparable in all respects. There was no difference in the objective response rate to either drug, Trilostane 11/38 = 29%, Aminoglutethimide 12/34 = 35%, nor in the average time to disease progression for the two drugs, Trilostane 64 weeks, Aminoglutethimide 68 weeks. Of the 26 patients who received both drugs, four showed a response to both suggesting no cross resistance. Side effects were seen to both drugs in approximately half of the patients, but were mainly gastro-intestinal with Trilostane and rash and drowsiness with Aminoglutethimide. There was no evidence of cross over patient susceptibility to side effects.
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Casodex, a pure potent non-steroidal anti-androgen, has been shown in a phase II clinical trial program to be very well tolerated and to have fewer side-effects compared with other anti-androgens. The most commonly reported side-effects (prompted by direct questioning) were breast tenderness (63.4%), breast swelling (52.5%), and hot flashes (23.6%). Gastrointestinal disturbances, hepatic impairment, alcohol intolerance, and problems with light adaptation are not associated with Casodex treatment. In this study, Casodex (50 mg once daily) was evaluated in 267 patients, 130 of whom have received it for more than 1 year. On assessment of best objective response, 55.5% of patients showed partial regression, 15.6% stable disease, 17.1% progression, and 11.8% were not assessable. These results are comparable with other standard hormonal therapies for advanced prostate cancer.
Eighteen patients with advanced metastatic carcinoma of the breast who had been previously treated with other hormone therapy were treated with stanozolol in a pilot study to assess its efficacy and toxicity. In a heavily pretreated population of patients with advanced breast cancer, three patients (16.6%) had partial responses (PR) and five patients (27.7%) had stable disease (SD). Toxicity was far less than that expected with androgen therapy. Stanozolol should be investigated in large groups of patients to establish its role more fully in the management of metastatic breast carcinoma.
A prospective randomized trial was conducted to compare the effects of the nonsteroidal antiandrogen flutamide (250 mg. 3 times daily) plus the luteinizing hormone-releasing hormone analogue goserelin acetate (Zoladex) (3.6 mg. subcutaneous depot injection every 28 days) with goserelin acetate alone in advanced prostatic carcinoma. A total of 571 eligible patients, of whom 57% had distant metastases, showed no difference in subjective or objective response rates, interval to progression, treatment failure or survival after a median followup of 2 years. In the combination group more patients had an early decrease in elevated levels of tumor markers and the small number of patients with an increase in signs and symptoms within the first 4 weeks showed a significant decrease. However, increased gastrointestinal and hepatic toxicity in the combination group resulted in 44 patients being withdrawn from the trial. These results indicate that the combination of goserelin acetate with flutamide provides no long-term clinical benefit in patients with advanced prostatic carcinoma compared to goserelin acetate alone.
A total of 23 patients with previously untreated Hodgkin's disease received MOPP/ABVD hybrid chemotherapy and response to treatment and toxicity were assessed. Of these 14 (61% (95% confidence limits 38.5%-80%] achieved complete remission with chemotherapy alone, six (26% (10.2%-48.4%)) achieved partial remission and there were three treatment failures (13%). Toxicity was mainly haematological resulting in treatment delays and dose reductions. Those in partial remission after chemotherapy achieved complete remission with additional radiotherapy. So far five of the 20 who remitted (25%) have relapsed. We conclude that the haematological toxicity from this regimen compromises dose intensity. The results from using this hybrid regimen are not superior to those using MOPP or ABVD alone in our experience.
Between November 1983 and February 1986, 358 patients with previously untreated metastatic prostatic carcinoma entered a multicentre, randomised trial in the United Kingdom and the Republic of Ireland, in which the LHRH analogue Zoladex (ICI Pharmaceuticals PLC), administered subcutaneously every 28 days, was compared with orchiectomy. Both treatments were equally effective in lowering serum testosterone concentrations to within the surgically castrate range and this was accompanied by equivalent subjective and objective response rates and times to treatment failure. At a median follow-up of 2 years there was no difference in overall survival, confirming that Zoladex is an effective medical alternative to orchiectomy in patients with metastatic disease.
A series of 22 patients with advanced carcinoma of the prostate who had failed first-line hormonal therapy (orchiectomy, stilboestrol, luteinising hormone-releasing hormone agonist) were treated with 160 mg megestrol acetate daily. Treatment was well tolerated, side effects were minimal and 21 patients were evaluable. There were no complete or partial responses, although 8 patients had a good subjective response. In 6 patients the disease was stabilised for 6 to 12 months and there was a 40 to 50% reduction in their prostatic acid phosphatase (PAP) levels. It was concluded that megestrol acetate has a role as second-line hormonal therapy in the management of prostatic carcinoma.
Acinic cell carcinoma represents 2.5% of all parotid neoplasms. Experience in its management is limited and its initial clinical diagnosis may be incorrect. This paper examines six patients who received less than ideal primary surgical care. Duration of follow up ranges from 1.25 years to 10.5 years, mean 6.7 years. Prophylactic postoperative radiotherapy appears to be of marked benefit in preventing recurrence and cervical node metastases.
Raynaud's phenomenon of varying severity is not uncommon following cytotoxic chemotherapy especially when combinations including bleomycin are used. We present a case in which severe Raynaud's progressing to trophic ulceration was successfully managed by dorsal sympathectomy.
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Idarubicin (4-demethoxydaunorubicin: DMDNR) is an orally active analogue of daunorubicin that has shown promising activity in animal and early clinical studies. We gave idarubicin in a phase II study to patients with advanced breast cancer unresponsive to hormonal manipulation and in some cases to standard chemotherapeutic agents. Idarubicin was given orally every 21 days at a starting dose of 40 mg/m2 with dose escalation until myelosuppression occurred. Nadir blood counts showed that patient compliance was good. Of 33 patients studied, 32 are evaluable for response: 4 (13%) had partial responses (95% confidence interval 1%-23%) with a duration of response between 32 and 59 weeks; 8 (25%) had static disease for between 17 and 48 weeks; and 20 failed to respond. For patients not previously exposed to chemotherapy, the response rate was 3/19 (16%). Toxicity was mild, with little or no gastro-intestinal disturbance in the majority of patients, no severe haematological toxicity and little alopecia. Two patients however, were withdrawn from the study because of toxicity; one with a skin rash and one with severe vomiting. Idarubicin produces little toxicity when given orally at a dose of 40 mg/m2 every 21 days, but its activity in breast cancer is insufficient to justify its further use with this schedule. Further studies should be undertaken only if direct comparison can be made with doxorubicin.
Primary nasopharyngeal involvement with Hodgkin's Disease (HD) is a rare event. Most such cases are associated with other sites of involvement. In this paper we present a case of Stage 1 HD in the nasopharynx and review the literature.
Three patients with cardiac tamponade secondary to disseminated breast carcinoma were treated by pericardiocentesis followed by systemic cytotoxic chemotherapy. This approach controlled pericardial effusion in all the patients and extended their survival.
The markers for testicular cancer, alpha-fetoprotein and human chorionic gonadotrophin, were measured in spermatic vein and peripheral blood taken at the time of orchiectomy. In all cases where markers were produced by the tumour, concentrations were found to be higher in spermatic vein than in peripheral blood, presumably because the former drains from the site of the tumour and dilution in the circulation has not yet occurred. Such measurements could be of particular value in patients whose tumours produce such small amounts of marker(s) that they are below the level of detection in peripheral blood.