H.-E. Wander

Aminoglutethimide in the treatment of premenopausal patients with metastatic breast cancer

Eighteen premenopausal patients with progressive metastatic breast cancer were treated with aminoglutethimide (AG)/cortisone. All patients received 1000 mg AG per day in combination with 2 X 25 mg cortisone acetate. Complete (CR) and partial remissions (PR) were achieved in 27.8%, a no change (NC) in 16.7% and progressive disease (PD) in 55.5% of all cases. The clinical results show that AG/cortisone acetate is effective in the therapy of premenopausal as well as postmenopausal patients with metastatic breast cancer. One hormone receptor negative tumour completely responded. Contrary to postmenopausal patients whose low oestradiol levels continuously decrease, oestradiol levels in premenopausal patients were not influenced by treatment. A distinct suppression of the ovarian activity does not occur. Thus concluding, a mechanism--at least partially different from those in the postmenopause and not necessarily of endocrine nature--must exist in the premenopause. We, therefore, no longer think it justified to assert that the therapeutic effect of AG is merely based on medical adrenalectomy.

Phase II study with etoposide in previously untreated advanced breast cancer

SummaryA phase II study was carried out to evaluate the efficacy and safety of etoposide used as first-line chemotherapy for patients with advanced breast carcinoma. A total of 20 patients received 230 mg/m2 i.v. etoposide per day for 3 days (total, 690 mg/m2 per course) every 4 weeks. A total of 95 courses were given. Observed responses included 3 partial remissions (PR) and 14 cases of stable disease (NC). The median duration of response was 6 (PR) and 5.6 months (NC). Contrary to the severe hematological toxicity in heavily pretreated patients described in previous studies, no substantial problems were observed in this trial. No dose reduction was necessary, and only once did leukopenia lead to a 1-week delay in therapy. An increase in platelets up to a maximum of 685,000/mm3 was seen in all patients, particularly in those with bone metastases. No relation to the quality of remission or pretreatment was seen. Nausea, vomiting, and fatique were mild and transient, but alopecia occurred in all cases. One patient developed nonfatal anaphylactic shock after etoposide treatment.

Megestrolazetat in verschiedenen Dosierungen bei der Behandlung des metastasierenden Mammakarzinoms — Klinische und endokrinologische Untersuchungen

SummaryBoth medroxyprogesterone acetate (MPA) and megestrol acetate (MA) are effective in the treatment of metastatic breast cancer. Although the dose-dependent mode of actions of MPA have been extensively clarified, there is still some uncertainty regarding the mode of actions and dosage of MA. Thirty-three patients with metastatic breast cancer were treated with various dosages of MA under a phase-II study. Eight patients were given 200 mg, 9×400 mg, 10×600 mg and 6×800 mg MA daily per os. The LH, FSH, TBI, T3, T4, TSH, ACTH, aldosterone, testosterone, prolactin and cortisol levels were determined regularly during treatment to enable the investigation of the pharmacodynamics of MA. A complete remission was achieved in two patients, a partial remission in seven patients and there was no change in eight patients (total responder rate 51.5%). The clinical and endocrine changes therefore suggest that the dose-dependent mode of actions of MPA and MA are identical. Equivalent dosages of MPA are 1000–1500 mg per os and of MA 160–200 mg. Furthermore, similar relationships between the endocrine changes and remission behaviour of MA and MPA have been observed. Persisting tumour remissions are inevitable under cortisol suppression and normal prolactin, aldosterone and ACTH levels.Both medroxyprogesterone acetate (MPA) and megestrol acetate (MA) are effective in the treatment of metastatic breast cancer. Although the dose-dependent mode of actions of MPA have been extensively clarified, there is still some uncertainty regarding the mode of actions and dosage of MA. Thirty-three patients with metastatic breast cancer were treated with various dosages of MA under a phase-II study. Eight patients were given 200 mg, 9 X 400 mg, 10 X 600 mg and 6 X 800 mg MA daily per os. The LH, FSH, TBI, T3, T4, TSH, ACTH, aldosterone, testosterone, prolactin and cortisol levels were determined regularly during treatment to enable the investigation of the pharmacodynamics of MA. A complete remission was achieved in two patients, a partial remission in seven patients and there was no change in eight patients (total responder rate 51.5%). The clinical and endocrine changes therefore suggest that the dose-dependent mode of actions of MPA and MA are identical. Equivalent dosages of MPA are 1000-1500 mg per os and of MA 160-200 mg. Furthermore, similar relationships between the endocrine changes and remission behaviour of MA and MPA have been observed. Persisting tumour remissions are inevitable under cortisol suppression and normal prolactin, aldosterone and ACTH levels.

Aminoglutethimide and medroxyprogesterone acetate in the treatment of patients with advanced breast cancer: A phase II study of the association of medical oncology of the German cancer society (AIO)

One hundred twenty‐eight women with advanced metastatic breast cancer were treated with a combination of aminoglutethimide (AG) (1000 mg orally, daily) and medroxyprogesterone acetate (MPA) (1500 mg orally, daily for six weeks and thereafter 500 mg orally, daily; omitting cortisone substitution). AG/MPA did not lead to side effects other than those described under AG or MPA monotherapy. Mental and personality changes seem to be more severe and frequent under combined therapy than under monotherapy. Impairment of mental functions, depressive syndromes, fatigue, ataxia, skin rash, and transient increase of gammaglutamyl transferase appeared and disappeared within the first 4 to 6 weeks of treatment. Objective remissions of at least 3 months duration from initiation of therapy were seen in 21 of 128 patients (21.9%) (3.9% complete remission [CR], 18% partial remission [PR]). A no change (NC) status occurred in an additional 25.8%. The remission duration (mean and range) was 19 (10.5–54) for CR, 16.5 (4.5–52+) for PR and 6 (3–27) months for NC patients. The highest response rate was registered for patients with only bone involvement (PR, 11; and NC, 11 of 26 patients). There was a distinct correlation of response to prior systemic treatment, receptor status of the primary tumor, disease‐free interval, menopausal status, age and condition of the patient. PR was obtained in 4 of 20 patients with receptor‐negative primary tumors. These results justify a prospective trial comparing AG/MPA with other forms of endocrine therapy in selected patient subgroups.

Medroxyprogesteronacetat als Glucocorticoid in der Kombination mit Aminoglutethimid zur Therapie des metastasierenden Mammakarzinoms

Eine wesentliche Wirkung des Medroxyprogesteronacetats ist die intrinsische glucocorticoidartige Aktivitat. Bei der Therapie des metastasierenden Mammakarzinoms mit hochdosiertem MAP konnte die cortisolartige Wirkung des MAP auch im Rahmen einer Langzeittherapie nachgewiesen werden. MAP supprimiert uber die zentrale ACTH-Hemmung die endogene Cortisolsekretion. Die cortisolartige Wirkung in holier Dosierung reicht aus, um die obligate Cortisolsubstitution bei der Therapie mit Aminoglutethimid zu ersetzen. Dies ermoglicht die Kombination zweier endokrin wirksamer Pharmaka in der Therapie des metastasierenden Mammakarzinoms.

Medroxyprogesteronacetat in hoher Dosierung beim metastasierenden Mammakarzinom

Im Rahmen der Therapie des metastasierenden Mammakarzinoms wurde MAP in verschiedenen Applikationsformen und Dosierungen eingesetzt. Dabei wurden pharmakokinetische und pharmakodynamische Untersuchung

Intensive short-term chemotherapy in patients with advanced breast cancer

SummaryAiming at a high complete remission rate with an intensive induction regimen, 27 patients with advanced breast cancer were given three cycles of VAC chemotherapy consisting of vinde-sine 3 mg/m2 i.v. on days 1 and 12, adriamycin 40 mg/m2 i.v. on days 1 and 12, and cyclophosphamide 200 mg/m2 p.o. on days 3–6 and 14–17 together with medroxyprogesterone acetate (MPA) 1,500 mg p.o. daily during the induction phase and 1,000 mg p.o. thereafter until relapse. These VAC double cycles were repeated twice with 3-weekly intervals for a total induction period of 15 weeks. In responders, including no change, the chemotherapy was discontinued thereafter, and the patients were observed until relapse with a maintenance therapy of MPA 1,000 mg p.o. daily.A complete remission (CR) was achieved in 8 (29.6%) and a partial remission (PR) in 13 (48.2%) of the 27 patients (CR + PR 77.8%). A no change (NC) status was found in 6 patients (22.2%). There were no nonresponders. The median duration of the CR was 20 (5–42) months with two patients still in CR at 33 and 36 months, of the PR 8.3 (4–13.5) months, and of the NC 6.7 (2–13) months. The treatment was tolerated without life-threatening toxicity or interval prolongation by all patients. No dose-limiting cardiac toxicity was observed in these patients regularly controlled by left ventricular ejection fraction (LVEF). The high response rate of this intensive induction regimen warrants further investigation. Complete remission was achieved only in patients without previous chemotherapy, with marked tumor regression after the first chemotherapy cycle and when there was no extensive bone involvement.

Monotherapy with idarubicin (4-demethoxy-daunorubicn) in advanced breast cancer (ABC)

Patients who have been treated successfully for metastases from breast cancer invar iab ly suffer from fur ther metastases. Due to th is less than sat is fac tory resul t 2 none cross-react ive chemotherapies were introduced in 1976 namely Adriamycin and Vincr is t ine in addit ion to Cyclophosphamide, Methotrexate and Fhorourac i l as part of the so cal led Second-line therapy. The remission rate has been subsequently reported to be between 20 an 50 %. A paucity of information ex is ts for drugs used in Th i rdl ine therapies. We have treated 40 pts. undergoing the Th i rdl ine treatment, 15 experienced a new remission, 13 of which were par t ia l remissions and 2 were complete remissions. Tumorreduction was observed in 8 pts, although th is reduct ion was less than 50 %. The average remission rate was 6.5 months however remissions up to 19 months were observed. In spi te of the massive Second-line therapy which normally included 2 cy tos ta t ic agents, hormone and radiat ion therapy, general to le ra t ion was good. The most prominent sideef fect were bone marrow t o x i c i t y and erythropoesis. Blood transfusions were therefore indicated for those patients in remission who undergo long-term chemotherapy. Th i rdl ine therapy in metastasizing breast cancer with MitomycLn, V incr is t ine and Prednison resulted in a 37 % remission rate with a good subject ive tolerance to the s ide-ef fects of the drugs.

Leucocyte nadir adapted chemotherapy (LNAC) in patients (PTS) with advanced breast cancer (ABC) (VAC/MPA versus VEC/MPA)

Patients who have been treated successfully for metastases from breast cancer invar iab ly suffer from fur ther metastases. Due to th is less than sat is fac tory resul t 2 none cross-react ive chemotherapies were introduced in 1976 namely Adriamycin and Vincr is t ine in addit ion to Cyclophosphamide, Methotrexate and Fhorourac i l as part of the so cal led Second-line therapy. The remission rate has been subsequently reported to be between 20 an 50 %. A paucity of information ex is ts for drugs used in Th i rdl ine therapies. We have treated 40 pts. undergoing the Th i rdl ine treatment, 15 experienced a new remission, 13 of which were par t ia l remissions and 2 were complete remissions. Tumorreduction was observed in 8 pts, although th is reduct ion was less than 50 %. The average remission rate was 6.5 months however remissions up to 19 months were observed. In spi te of the massive Second-line therapy which normally included 2 cy tos ta t ic agents, hormone and radiat ion therapy, general to le ra t ion was good. The most prominent sideef fect were bone marrow t o x i c i t y and erythropoesis. Blood transfusions were therefore indicated for those patients in remission who undergo long-term chemotherapy. Th i rdl ine therapy in metastasizing breast cancer with MitomycLn, V incr is t ine and Prednison resulted in a 37 % remission rate with a good subject ive tolerance to the s ide-ef fects of the drugs.

Panmyelopathie unter Aminoglutethimid

Aminoglutethimid hemmt im adrenalen und nicht-adrenalen Gewebe die Ostrogensynthese und wird erfolgreich in der Behandlung des metastasierenden Mammakarzinoms eingesetzt. Als seltene, aber ernste Nebe