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Biomedical subjects

J H Waxman

Publications and source records attributed to J H Waxman.

17 recordsLinked to original sources

Kinetics, quantitative analysis and radioimmunolocalization using indium-111-HMFG1 monoclonal antibody in patients with breast cancer.

HMFG1 tumour associated monoclonal antibody IgG1 and F(ab')2 fragments were radiolabelled with indium-111 and used to study patients with breast cancer. In vitro and in vivo stability of the radiolabelled antibodies was shown to be satisfactory. Thirty patients with primary breast cancer underwent tumour resection and quantitative evaluation of the radioactivity in the tumour and normal tissues following administration of specific and non-specific antibodies. The mean tumour uptake of HMFG1 F(ab')2 fragments at 24 h was significantly higher (P less than 0.05) than the intact IgG but at 48 h there was no difference. The mean tumour uptake with the specific antibody was higher than the non-specific antibody of the same subclass (P less than 0.05). Lymph node metastases showed higher antibody uptake than the corresponding primary tumours (P less than 0.05). Fifteen patients with primary or metastatic breast cancer were investigated by external body scintigraphy using HMFG1 F(ab')2 fragments. Successful localisation was observed in approximately 50% of the primary and metastatic lesions with no false positive results. All the patients had observable concentration of 111In in the liver (20% of the injected dose), the kidneys and the spleen. Following i.v. administration, F(ab')2 fragments cleared from the blood more rapidly than the intact IgG. We conclude that HMFG1 F(ab')2 fragments can localise specifically and faster than intact IgG in breast cancer but the sensitivity of the radioimmunoscintigraphy is relatively low. This method needs further improvement before becoming clinically useful for detecting and staging breast cancer.

Adult↗

Two-monthly depot gonadotropin releasing hormone agonist (buserelin) for treatment of prostatic cancer.

The agonist analogues of gonadotropin-releasing hormone provide an alternate medical therapy for prostatic cancer. Current methods of administration of these analogues by daily injection or nasal spray is sub-optimal in an elderly population. We have performed a pharmacological and endocrine evaluation of a new depot preparation of one such analogue, buserelin, active for 2 months. Thirty patients with advanced symptomatic prostatic cancer were treated. Serum testosterone was suppressed for the duration of treatment which ranged up to 14 months. The release characteristics of the depot were consistent and showed minimal variation between patients. This 2-month preparation of buserelin offers and advantage to the patient with prostatic cancer, over current treatment regimens.

Adult↗

Failure to preserve fertility in patients with Hodgkin's disease.

The hypothesis that the "down-regulated" gonad is less vulnerable to the effects of cytotoxic chemotherapy for advanced Hodgkin's disease has been investigated. Thirty men and eighteen women were randomly allocated to receive an agonist analogue of gonadotrophin-releasing hormone prior to, and for the duration of, cytotoxic chemotherapy. Buserelin (d-Ser-[TBU]6 LHRH ethylamide) was prescribed in two different dosage schedules to twenty men, and in a single dosage schedule to eight women. A standard gonadotrophin-releasing hormone test (GnRH 100 micrograms) was performed 1 week prior to and on day 1 of each cycle of chemotherapy. In all patients peak luteinizing hormone responses to GnRH were suppressed throughout treatment. The higher of the two dosage schedules used in the men caused more effective suppression of luteinizing hormone, and both regimens led to an initial suppression of peak follicle-stimulating hormone responses to GnRH, which was not maintained. At follow-up assessment up to 3 years from the completion of treatment, all men treated with buserelin were profoundly oligospermic and four of the eight women were amenorrhoeic. All ten male controls were profoundly oligospermic, and six of nine female controls were amenorrhoeic. In the dosages and schedules investigated, buserelin was ineffective in conserving fertility.

Amenorrhea↗

EVA treatment for recurrent or unresponsive Hodgkin's disease.

Nineteen patients with recurrent or unresponsive Hodgkin's disease who had previously received combination chemotherapy comprising mustine or chlorambucil with vinblastine, prednisolone and procarbazine (MVPP or ChlVPP), were treated with a combination of etoposide, vincristine and adriamycin (EVA). Clinical remission (complete, CR + good partial, GPR) was achieved in eleven of the nineteen patients (58%). The remission rate was similar for patients who had previously responded well to chemotherapy and for those who had previously been poorly responsive. Six patients have relapsed between 3 and 5 months after completion of therapy. The remainder continue in remission, two without further therapy at 7 and 8 months, respectively, and three having had additional radiotherapy while in remission. Myelosuppression was the most important toxicity, but in general this was manageable. These results suggest that EVA may be non-cross-resistant with MVPP and ChlVPP and that it is of potential value in combination chemotherapy for previously untreated patients, even though it is unlikely to be curative when treatment with either MVPP or ChlVPP has failed.

Adolescent↗

The first clinical use of depot buserelin for advanced prostatic carcinoma.

The agonist analogues of the gonadotrophin-releasing hormone now provide an alternate medical treatment of prostatic cancer. For effect repeated administration is required, either by five or six times daily intranasal or once daily subcutaneous treatment. There is an obvious disadvantage to such regimens in elderly patients who may have difficulty complying with therapy. In order to circumvent these difficulties, sustained release formulations of the agonist analogues have been synthesized. We report the first clinical use of a long-acting formulation of D-Ser (TBU)6-LHRH Ethylamide (buserelin) using a novel polymer material. Twelve symptomatic patients with previously untreated carcinoma of the prostate were treated with depot buserelin, administered once monthly. In all patients, depot buserelin suppressed serum testosterone into the range seen in castrate men at a rate equivalent to that provided by five times daily intranasal therapy. No significant increase in serum testosterone, luteinizing hormone or follicle-stimulating hormone concentrations occurred during the period of follow-up. Long-acting formulations of buserelin offer an advance in the management of prostatic cancer with agonist analogues of the gonadotrophin-releasing hormone.

Aged↗

The treatment of postmenopausal women with advanced breast cancer with buserelin.

Repeated administration of long-acting analogues of gonadotrophin-releasing hormone down-regulates the pituitary gonadotrophins and gonadal hormones. The activity of these compounds in premenopausal women with breast cancer has been previously noted. In an attempt to cause a highly selective medical hypophysectomy 18 consecutive postmenopausal women with symptomatic advanced breast cancer were treated with intranasal buserelin in divided dosages of either 600 or 1000 micrograms daily. The pituitary gonadotrophins were suppressed in all patients, without objective evidence of response. This is in contrast with an earlier finding that the long-acting analogues of gonadotrophin-releasing hormone were effective in postmenopausal patients with breast cancer.

Adenocarcinoma↗

A long term follow-up of patients with advanced prostatic cancer treated with buserelin.

Thirty consecutive patients with newly diagnosed symptomatic, locally advanced or metastatic prostate cancer were treated with intranasal buserelin, a long-acting analogue of gonadotrophin releasing hormone, in divided dosages of either 600, 1000 or 1200 micrograms daily. Suppression of testosterone occurred in 1 of 5 patients treated with 600 micrograms daily and in all of 25 patients receiving 1000 or 1200 micrograms regimens. Two of 5 patients treated with the 600 micrograms regimen and 23 of 25 patients receiving the higher dosage regimens showed subjective and objective evidence of response. Follow-up was from 1 to 31 months. During this period 11 patients have relapsed. The mean duration of remission was 16 months. Buserelin offers an effective alternative of equivalent efficacy to conventional treatments for prostatic cancer, without any significant side effects.

Buserelin↗

Treatment with gonadotrophin releasing hormone analogue in advanced prostatic cancer.

Repeated administration of long acting analogues of gonadotrophin releasing hormone diminishes gonadal function and in men decreases testosterone concentrations; for this reason the effect of the analogue buserelin was studied in prostatic carcinoma. Twelve consecutive patients with newly diagnosed locally advanced or metastatic carcinoma of the prostate were treated. Each patient received intranasal buserelin in divided dosages of either 600 or 1000 micrograms daily. Suppression of the gonadotrophins and testosterone occurred in all patients. Objective and subjective signs of regression of disease were seen in nine patients. Buserelin offers an effective treatment of metastatic prostatic cancer without the side effects and cardiovascular risks associated with oestrogen treatment.

Administration, Intranasal↗

Treatment of advanced prostatic cancer with buserelin, an analogue of gonadotrophin releasing hormone.

Twenty-two consecutive patients with newly diagnosed symptomatic, locally advanced or metastatic prostate cancer were treated with intranasal buserelin, a long-acting analogue of gonadotrophin releasing hormone, in divided dosages of between 600 and 1000 micrograms daily. Suppression of testosterone occurred in 1 of 5 patients treated with 600 micrograms daily and in all 17 patients receiving 1000 micrograms daily. Two of 5 patients treated with the 600 micrograms regimen and 16 of 17 patients receiving the 1000 micrograms regimen showed subjective and objective evidence of disease regression. Follow-up was from 1 to 16 months (mean 7.1 months); 6 patients have relapsed during this period. Buserelin offers an effective alternative medical treatment of carcinoma of the prostate and, apart from impotence, does not have the side effects of oestrogens.

Administration, Intranasal↗

Gonadal function in Hodgkin's disease: long-term follow-up of chemotherapy.

A long-term study of gonadal function was conducted in 46 men and 28 women in prolonged remission of advanced Hodgkin's disease after cyclical combination chemotherapy with nitrogen mustard, vinblastine, prednisolone, and procarbazine. The mean follow-up was 6.9 years. Azoospermia or profound oligospermia occurred in 36 of the men, but late recovery was occasionally observed. Testosterone secretion was preserved. Amenorrhoea and gonadal hormone deficiency developed in 22 of the women and never recovered. Partial or complete chemical sterilisation and gonadal hormone deficiency is currently a consequence of cure of advanced Hodgkin's disease in most patients.

Adolescent↗

OPEC chemotherapy (vincristine, prednisolone, etoposide and chlorambucil) for refractory and recurrent Hodgkin's disease.

Fifteen adults with refractory or recurrent Hodgkin's disease were treated with a combination of: vincristine, prednisolone, etoposide and chlorambucil (OPEC). All had previously received mustine, vinblastine, procarbazine and prednisolone (MVPP) and seven had subsequently been treated with alternative regimens. Responses were achieved in four, but complete remission in only one. Toxicity was considerable and five died of treatment related complications. Only two are alive (one in complete remission) more than three years after therapy. The toxicity of the OPEC regimen outweighed its benefit in this group of poor prognosis patients.

Adolescent↗