Randomized trial of low-dose chemotherapy added to tamoxifen in patients with receptor-positive and lymph node-positive breast cancer.

PURPOSE: To evaluate the outcome in patients with stage II hormone receptor-positive breast cancer treated or not treated with low-dose, short-term chemotherapy in addition to tamoxifen in terms of disease-free and overall survival. PATIENTS AND METHODS: A total of 613 patients were randomized to receive either low-dose chemotherapy (doxorubicin 20 mg/m(2) and vincristine 1 mg/m(2) on day 1; cyclophosphamide 300 mg/m(2); methotrexate 25 mg/m(2); and fluorouracil 600 mg/m(2) on days 29 and 36 intravenously) or no chemotherapy in addition to 20 mg of tamoxifen orally for 2 years. A third group without any treatment (postmenopausal patients only) was terminated after the accrual of 79 patients due to ethical reasons. RESULTS: After a median follow-up period of 7.5 years, the addition of chemotherapy did not improve the outcome in patients as compared with those treated with tamoxifen alone, neither with respect to disease-free nor overall survival. Multivariate analysis of prognostic factors for disease-free survival revealed menopausal status, in addition to nodal status, progesterone receptor, and histologic grade as significant. Both untreated postmenopausal and tamoxifen-treated premenopausal patients showed identical prognoses significantly inferior to the tamoxifen-treated postmenopausal cohort. Prognostic factors for overall survival in the multivariate analysis showed nodal and tumor stage, tumor grade, and hormone receptor level as significant. CONCLUSION: Low-dose chemotherapy in addition to tamoxifen does not improve the prognosis of stage II breast cancer patients with hormone-responsive tumors. Tamoxifen-treated postmenopausal patients show a significantly better prognosis than premenopausal patients, favoring the hypothesis of a more pronounced effect of tamoxifen in the older age groups.

Randomised phase II study of epirubicin-vindesine versus mitoxantrone-vindesine in metastatic breast cancer.

The purpose of this study was to compare the activity and toxicity of epirubicin-vindesine (EV) with mitoxantrone-vindesine (MV) in patients with metastatic breast cancer. A total of 295 patients was randomly allocated to treatment with vindesine 3 mg/m2 combined with either epirubicin 40 mg/m2 or mitoxantrone 10 mg/m2. All drugs were given by intravenous push, treatment cycles were repeated at 3-4 week intervals. 255 patients were available for response, and 283 for toxicity. EV and MV yielded similar objective response rates (34 and 26%, respectively), response durations, times to progression and survival. Median time to remission was 1.8 and 3.1 months (P = 0.006) with EV and MV, respectively. In patients with visceral metastases, response rate was higher with EV than MV (40 versus 23%; P = 0.03). Patients receiving MV had less nausea/vomiting (P = 0.007) and alopecia (P = < 0.001) of WHO grade > or = 2. Bone marrow, cardiac and other toxicities were mild with both treatments. The observed differences in activity and toxicity between the two regimens appear to have clinical relevance. EV proved to be more active in visceral disease and to be able to induce remissions more rapidly. Accordingly, patients with visceral metastases or severe tumour-related symptoms may benefit from epirubicin-based treatment. Subjective toxicities, i.e. nausea/vomiting and alopecia, were less frequent and severe with MV. Thus, MV may prove useful in patients with more indolent disease and appears to warrant phase III evaluation in such patients.

Clinical studies of Ukrain in terminal cancer patients (phase II).

Phase II of clinical studies was performed on 70 patients, ranging in age from 14 to 80 years, (27 male, 43 female) to determine the appropriate dose range for Ukrain and the clarification of dose/response relationships, in order to provide an optimal background for wider therapeutic trials. The following parameters were studied: physiological (pulse, blood pressure, temperature); biochemical, haematological and immunological. Electrolytes and trace elements were investigated, as well as neopterin, tumour markers, immune complexes, non specific blocking factors, development of tumours and metastases in quantitative respects (by X-ray, CT, scintigrams and US). The patients' general conditions were also assessed. Ukrain was given intramuscularly or intravenously every one, two, three, four or five days, or according to other schemata, in the dose range of 2.5, 5, 10, 15, 20 or 25 mg increasing (2.5 to 25 mg per injection), decreasing (25 to 2.5 mg per injection) and stable (5, 10, 15, 20 or 25 mg per injection). Duration of one course of therapy was between 10 days and 90 days. Intervals between courses ranged from 7 days to 3 months. In order to find dose/duration/interval/response-relationships, some cases were treated after chemoradiotherapy, some as adjuvant therapy to chemo-radiotherapy and alternatives such as iscador, and some as monotherapy. All patients were at terminal stages of their disease.

Vindesine-epirubicin versus vindesine-mitoxantrone in metastatic breast cancer.

UNLABELLED: The present study was designed to assess the toxicity and efficacy of two chemotherapy protocols in patients with metastatic breast cancer. Starting in December 1985, 230 patients were randomized to receive vindesine (V) (3 mg/m2 i.v.) and mitoxantrone (M) (10 mg/m2 i.v.) or V and epirubicin (E) (40 mg/m2 i.v.) every 3 weeks x 3 and every 4 weeks thereafter. Patients were stratified according to site of disease (visceral, bone or soft tissue dominant) and prior therapy. Patient groups were comparable with respect to menopausal status, age, estrogen receptor status and disease-free interval. About two-thirds of the patients presented with visceral recurrence and 30% with bone lesions: only 8% had soft tissue metastases. RESULTS: We observed a significant difference (p = 0.003) in the frequency of alopecia (WHO grade 3-4, 36% vs. 60% favoring regimen VM); gastrointestinal and hematologic side effects and neurotoxicity were mild and similar for both groups. In 182 evaluable patients there was a 26% response rate (CR + PR. UICC criteria) for VM and 35% for VE (not significant). NC was observed in 37% and 43% of patients treated with VM or VE respectively. There was no significant difference between these two groups with regard to time to progression and survival. The median time of follow-up was 8 months and therefore too short to draw definite conclusions. Both regimens were well tolerated and seem to be equally effective, although the response rate for VM and VE was lower than expected.

Steroid hormone receptors and prognosis in breast cancer.

The importance of steroid receptors for the prognosis of mammary carcinoma has been evaluated by investigating the course of disease in 163 patients for a median follow up time of 66 months after mastectomy. Multivariate analysis including estrogen receptor (ER), progesterone receptor (PgR), the presence of 8S and 4S ER together or 4S ER only, and the lymph node status revealed only the latter to have significant (p less than 0.001) predictive potency. Lymph node positive (N-pos) patients had a 3.3 (1.7-6.2) fold risk of death and 2.8 (1.7-4.7) fold risk of recurrence relative to node negative (N-neg) patients. When we compared overall survival (OAS) and disease-free survival (DFS) in the various receptor-positive groups with the groups that displayed neither ER nor PgR, significant differences in prognosis were only seen in N-neg patients. PgR did not turn out to be a better prognostic factor than ER, nor was the 8S ER a sign of increased OAS and DFS compared to total ER. However, the number of patients in this group was too small to allow a definite statement.

[Sonographic detection of intracystic breast tumors]. / Sonographischer Nachweis intrazystischer Mammatumoren.

While simple breast cysts account for the most common benign lesions of the breast, intracystic tumours, which most frequently occur as papillomas and papillary adenocarcinomas, are rare. In this paper we report on the clinical picture of these tumours, using our own material, and discuss the relevance of sonography in pre-operative diagnosis compared to conventional examination techniques such as mammography and pneumocystography.

[Comparison between the biochemical and histochemical determination of hormone receptors in breast carcinomas]. / Vergleich zwischen biochemischer und histochemischer Hormonrezeptorenbestimmung bei Mammakarzinomen.

The hormonal sensitivity of breast cancer on one hand indicates the prognosis and on the other determines the therapeutical procedure when metastases appear. It also seems to be important in the choice of adjuvant therapy. Therefore the analysis of hormonal receptors in our opinion is at least as important as the histological typification of the carcinoma. As there was a trend recently showing up the so-called histochemical steroid-receptor-assay which is much less complicated than the biochemical (quantitative) method, we investigated the value of this fluorescence-microscopical assay by means of parallel determinations. In the results of 157 patients of the last three years we found differences in 45% of all oestrogen-receptor-determinations and in 50% of 29 progesterone-receptor-determinations. This indicates that the histochemical assay is most probably not representative. There is serious doubt about the possibility to document the hormone receptor by this method at all. Therefore it does not seem advisable at the moment to waive the biochemical receptor determination.

[Combined surgical and radiological therapy of pancreatic cancer--case report--future aspects]. / Chirurgisch-radiologisch kombiniertes Therapieverfahren beim Pankreaskarzinom--Falldemonstration--Zukunftsaspekte.

On the basis of the literature [1, 3-5], combined surgical management and intraoperative radiotherapy of carcinoma of the pancreas is demonstrated and illustrated by a case report and further aspects are discussed.