High dose medroxyprogesterone acetate (MPA) treatment in metastatic carcinoma of the breast: a dose-response evaluation.

The results of controlled clinical trial that used high doses of medroxyprogesterone acetate (MPA) in the treatment of metastatic breast cancer are reported. Two treatment reigmens were used: regimen A, 500 mg daily with a total dose of 30 g; regimen B, 1,000 mg daily with a total dose of 60 g. The overall response rates were similar, with no statistically significant difference between the two treated groups. Regimen A (lower dosage group) reached a remission rate of 44%, whereas regimen B (higher dosage group) had a remission rate of 41%. The mean duration of response was 8 months with regimen A and 9 months with regimen B. The advantages of the lower dosage regimen as opposed to the higher dosage regimen of MPA in the treatment of advanced breast cancer are discussed.

PIP: A controlled clinical trial that used high doses of medroxyprogesterone acetate (MPA) in the treatment of metastatic breast cancer was conducted. Therapy consisted of 2 treatments: regimen A, 500 mg daily with a total dose of 30 g; regimen B, 1000 mg daily with a total dose of 60 g. From June 1975 to September 1976, 101 patients entered into the study and were randomly allocated into the 2 treatment groups. Both treatment groups were comparable in terms of age, menopausal status, free interval, and dominant site of lesions. Selection of patients was done according to the following criteria: histologically proved progressive metastatic carcinoma of the breast, without any treatment for at least 2 months; no prior hormonal manipulation; performance status 50 or more, and life expectancy longer than 3 months; measurable disease. Overall response rates were similar, with no statistically significant difference between the 2 treated groups. Regimen A reached a remission rate of 44%; regimen B had a remission rate of 41%. The mean duration of response was 8 months with regimen A and 9 months with regimen B. Both regimens were well tolerated. Clinical toxicity was mild with both dosages of MPA. The main side effect was gluteus abscess, with a higher incidence in group B. This was probably due to the greater amount of injected drug suspension in the 1000 mg/day regimen. The incidence of thrombophlebitis and vaginal bleeding was negligible.

Vinorelbine as single agent in pretreated patients with advanced breast cancer.

Vinorelbine is a new semisynthetic vinca alkaloid with high activity against breast cancer. In this multicenter clinical study we evaluated the activity and toxicity of vinorelbine as a single agent in 30 advanced breast cancer patients pretreated with anthracycline and/or mitoxantrone (24 with recurrent tumor, 6 with non operable cancers). Vinorelbine was given at a weekly dose of 20 mg/m2 for a minimum of 3 weeks. Treatment was continued until there was disease progression or evidence of serious toxicity. Predominant sites of metastasis were viscera (14 cases), soft tissue (11 cases) and bone (5 cases). A median number of 12 doses of vinorelbine (range 3-34) were administered to each patient. Objective responses were recorded in 11 of them and 15 had minimal responses or stable disease. Four patients showed progression of disease during vinorelbine chemotherapy. The median duration of response was 5 months (2-14). The median survival time was 7 months (2-20+): 9 months for responders and 5 months for those with stable or progressive disease. The most important and dose-limiting toxicity was represented by leukopenia. The compliance of patients was very good and the treatment was well accepted by them all including those with low performance status. In conclusion, this study provides further evidence that a weekly schedule with vinorelbine as a single agent is effective and well-tolerated also in pretreated advanced breast cancer patients.

[Calusterone (7-beta, 17-alpha-dimethyltestosterone) in the palliative treatment of advanced breast cancer]. / Il calusterone (7-beta, 17-alfa-dimetiltestosterone) nel trattamento palliativo del carcinoma mammario in fase avanzata.

Results in palliative treatment of advanced breast cancer with a new androgen, calusterone, are discussed. Sixty post-menopausal patients with metastatic breast carcinoma were treated with 200 mg per day at least three months. The overall response was 28% (17/60); better results seemed to be achieved in advanced post-menopausal patients with osseous and cutaneous lesions. These results agree with those reported by the Cooperative Breast Cancer Group. No undesirable side-effects were observed and calusterone was well tolerated.

[Oral high doses of medroxyprogesterone acetate (MPA) in the treatment of advanced phases of breast and endometrial cancer]. / Il medrossiprogesterone acetato (MPA) ad alta dose per via orale nel trattamento delle fasi avanzate del cancro mammario ed endometriale.

The results of a pilot study on the use of oral medroxyprogesterone acetate (Provera-Upjohn) at high dose in a series of 50 consecutive women with advanced breast (30 cases) and endometrial carcinoma (20 cases) are reported. Patients with progressive disease, non liable to further conventional treatments, received MPA (500 mg/day orally) for 90 days. The evaluation of results have shown only partial responses: in 9/30 (30%) of women with disseminated breast carcinoma (median duration of response 10 months, median survival 15 months), and in 6/20 (30%) of patients with advanced endometrial carcinoma (median duration of response 15 months, median survival not reached at 28 months of follow-up). Even if with a lower response rate, as compared to the results obtained with parenteral formulation, the oral MPA maintains its therapeutic effectiveness in these hormonodependent tumors: easy to handle during the long term treatments, oral MPA could be a useful alternative also for maintenance therapy.

PIP: 30 patients with advanced breast carcinoma, and 20 patients with advanced endometrial carcinoma were treated with high doses, 500 mg./day, of MPA (medroxyprogesterone acetate) administered orally for 3 months. Evaluation of results showed responses in only 30% of women treated, independently of the type of carcinoma. In the breast carcinoma group median duration of response was 10 months, and median survival time 15 months; in the second group of patients median duration of response was 15 months, and median survival time was not yet reached after 28 months of follow-up. Negative side effects were gain of body weight and hypertension; oral MPA administration seems to have a lower response rate than parenteral administration; it is, however, easier to handle, and could present a useful alternative in maintenance therapy.

[Evaluation of the capacity of work using upper limbs after radical latero-cervical surgery]. / La valutazione della capacità lavorativa con gli arti superiori dopo intervento di svuotamento latero-cervicale.

Evaluation of arm work capacity after radical neck surgery. The aim of this paper is to describe an approach for the assessment of work capacity in patients who underwent radical neck surgery, including those treated with radiation therapy. Nine male patients, who underwent radical neck surgery 2 months before being referred to our Unit, participated in the study. In addition to manual muscle strength test, we performed the following functional evaluations: 0-100 Constant scale for shoulder function; maximal shoulder strength in adduction/abduction and intrarotation/extrarotation; instrumental. We measured maximal isokinetic strength (10 repetitions) with a computerized dynamometer (Lido WorkSET) set at 100 degrees/sec. During the rehabilitation phase, the patients' mechanical parameters, the perception of effort, pain or discomfort, and the range of movement were monitored while performing daily/occupational task individually chosen on the simulator (Lido WorkSET) under isotonic conditions. On this basis, patients were encouraged to return to levels of daily physical activities compatible with the individual tolerable work load. The second evaluation at 2 month confirmed that the integrated rehabilitation protocol successfully increased patients' capacities and "trust" in their physical capacity. According to the literature, the use of isokinetic and isotonic exercise programs appears to decrease shoulder rehabilitation time. In our experience an excellent compliance has been noted. One of the advantages of the method proposed is to provide quantitative reports of the functional capacity and therefore to facilitate return-to-work of patients who underwent radical neck surgery.

Work capacity of the upper limbs after mastectomy.

Cancer patients are now more often long-term survivors and their needs for returning to social and productive activities have become a primary focus of intervention. The purpose of the present study was to propose an objective evaluation test for predicting endurance capacity in breast cancer patients after surgery, in order to optimize return to work or previous daily activities, and for monitoring changes during rehabilitation. Twenty female patients (mean age: 44 +/- 5), who underwent radical breast surgery 2 months before being referred to our Unit, participated in the study. In addition to the measures of the circumferences in the arm-forearm and manual muscle strength test, we performed the following functional evaluations: 0-100 Constant scale for shoulder function; instrumental evaluation of daily/occupational upper limb activities (Lido WorkSET). We monitored the mechanical parameters, the perception of effort, pain or discomfort, and the range of movement while performing a 3-minute steady daily/occupational task chosen by the subject. Patients were asked to perform the 3-minute test at three different intensities ("moderate", "somewhat hard", "hard") until the perception of fatigue, pain or discomfort was rated > 3 on the 10 point Borg's scale. The 'power-duration' product (Watt x min) defined by the three tests (see Fig. 1) represented the individual tolerable work load, since subjective indicators of pain/discomfort remained within tolerable limits during the exertion. On this basis, patients were encouraged to return to levels of daily physical activities compatible with the individual tolerable work load. The second evaluation, although no statistical analysis was performed, confirmed that the "guided" daily activity in a 2-month period increased patients' capacities and "trust" in their physical capacity.

Multidisciplinary treatment for central nervous system tumours with nitrosourea compounds.

The authors report the results of a controlled clinical trial in patients with primitive and metastatic CNS tumours treated with combined therapy: surgery, radiotherapy, and chemotherapy (BCNU or CCNU). A total of 102 patients were treated, 50 with BCNU, and 52 with CCNU. The overall response (R. + P.R.) was 68% for the BCNU group, and 65% for the CCNU group. No significant differences were found between the two types of treatment, either in terms of response or in terms of quality and length of survival.

Accumulation of 99m Tc-Sn-pyrophosphate in pleural effusions.

Accumulation of 99m Tc-Sn-pyrophosphate in pleural effusions has been evaluated in 56 patients grouped as follows: 8 with bacterial effusion (Group A), 27 with malignant effusion treated by local and/or parenteral antitumor chemotherapy (Group B), 21 with malignant effusion treated only by supportive therapy (Group C). Results, expressed as effusion to plasma PPi ratio, ranged from 0.1 to 0.28 in group A, from 0.04 to 0.64 in group B and from 0.60 to 1.73 in group C, with significant differences among the three groups. In no case was uptake found in cells of the sediment. Chemical analysis (including total and ionized calcium, total protein, acid and alkaline phosphatase) of plasma and exudate in neoplastic patients showed a slight, but significant, difference between groups B and C as regards plasma-effusion gradient for total calcium and acid phosphatase. Negative correlation also exists between effusion to plasma PPi ratio and plasma-exudate gradient for ionized calcium in neoplastic patients. The data support the hypothesis that acid phosphatase content and calcium gradient are among the factors involved in the mechanism of PPi accumulation in pleural effusions.

Ethinyl estradiol and medroxyprogesterone treatment in advanced breast cancer: a pilot study.

Twenty patients with disseminated breast cancer unresponsive to conventional chemotherapy and chemohormonotherapy were treated with an alternating sequential schedule of ethinyl estradiol and medroxyprogesterone on the basis of correlations between hormones and estrogen and progestin receptors. Of 19 evaluable patients, six underwent partial or complete remission, while five others showed minor responses.

PIP: A pilot study was conducted on 20 patients with disseminated breast cancer previously unresponsive to conventional chemotherapy and chemohormonotherapy. The 20 women were treated with ethinyl estradiol orally on days 1 and 2, medroxyprogesterone on days 3-9. After a 2-day interval, the sequential cycle was repeated. 10% of the women had complete remission and 20% more had partial remissions. More than 1/4 had minor remissions and 10% had their disease stabilized. Side effects with the therapy were practically absent. The rationale for the sequential therapy was suggested by interactions among hormones and receptors and the priming activity of estrogens on progesterone receptors. These preliminary results indicate that an alternated sequential therapy of ethinyl estradiol and medroxyprogesterone may be useful in managing advanced cancer.