Seventy-three patients with metastatic breast cancer, whose disease progressed on hormonal therapy with tamoxifen or aminoglutethimide, were treated with megestrol acetate, 160 mg/day. No complete responses were observed. Partial response was achieved in 3 patients (4%), for a median of 9 months (range 5-13). Thirty-five patients (48%) remained stable, for a median of 8 months (3-26). The remaining 35 patients (48%) had clear progression of their metastatic disease on therapy. Response to megestrol acetate was achieved in patients with metastases in bone and pleura only. There was no correlation between response to megestrol acetate and response to prior chemotherapy, prior tamoxifen therapy, previous treatment with aminoglutethimide, or hormone receptor status. The actuarial 24-month survival for all patients was 37%. The main side effects of megestrol acetate included weight gain (20% or over), pruritus, elevation of blood pressure, weakness, and vaginal bleeding; they were only occasionally observed. The objective improvement observed during this trial is disappointing; the only reasons to justify the use of megestrol acetate as second- or third-line hormonal therapy in patients with metastatic breast cancer, would be the relatively long duration of disease stabilization in a large proportion of patients, and the low toxicity observed with the drug.

Adult↗

PubMedDate not supplied

Functional and morphological alterations following isolated rat stomach irradiation. A model for estimation of radiation injury.

Exposure of the stomach to tumoricidal doses of radiation is associated with functional and morphological changes. The experimental data have been mainly obtained from studies of whole body irradiation of the stomach. We investigated the separate effect of irradiation on the surgically exposed stomach with doses of between 3 and 30 Gy. A dose-dependent decrease in free and total acidity was observed with relatively low doses (5-9 Gy). Serum pepsinogen and serum gastrin levels increased following irradiation with doses ranging from 5 to 15 Gy. Two phases of increased regenerative activity were documented (between the 1st and 3rd weeks and between the 4th and 8th weeks). No radioprotective effect was observed when sucralfate or misoprostol were utilized. Further investigations are mandatory in order to find an effective radioprotector for the irradiated stomach.

Animals↗

PubMedDate not supplied

Combination chemotherapy in metastatic tumors of unknown origin. 5-Fluorouracil, adriamycin and mitomycin C for adenocarcinomas and adriamycin, vinblastine and mitomycin C for anaplastic carcinomas.

Twenty-nine evaluable patients with metastatic carcinomatosis in whom initial workup failed to reveal the primary site were entered into this trial. Patients with histological evidence of adenocarcinoma (n = 15) received FAM, while patients with anaplastic carcinomas (n = 14) were given AVM. Pretreatment characteristics were similar for the FAM- and AVM-treated patients with regard to age and sex, but 47% of patients on FAM had liver metastases as compared with 36% for the AVM group. Of the 14 patients on AVM, 1 (7%) achieved a complete response lasting 16 months, and 3 patients (22%) achieved a partial response for 10, 12 and 20 months, respectively. No patient on FAM reached a complete response, and only two patients (13%) showed a partial remission for 7+ and 24 months, respectively. The median survival for the AVM patients was 8.5 months, not significantly different from a median of 5 months for the FAM-treated group. AVM caused substantial myelotoxicity, resulting in five hospitalizations for leukopenia and fever; the FAM regimen was better tolerated with no episodes of leukopenic fever. AVM appears to be more effective than FAM in the treatment of carcinomas of unknown origin. A higher response rate was achieved with AVM, despite the fact that patients on this combination had undifferentiated carcinomas and a larger proportion of three or more metastatic sites (36 vs. 13% on FAM), and received a lower percent of the planned dose than did the FAM patients. Further clinical trials to fully establish the role of vinblastine in the treatment of metastatic carcinomatosis of unknown origin seem warranted.

Adenocarcinoma↗

PubMedDate not supplied

Prognostic factors affecting treatment results with combination chemotherapy in metastatic breast cancer.

Seventy five patients suffering from metastatic breast cancer previously unexposed to chemotherapy were treated with Cyclophosphamide, Methotrexate and 5-fluorouracil (CMF) upon diagnosis of their first relapse. Dose Level I (85% or more of the planned dose) was given to 14 patients (19%); Dose Level II (66% to 84% of the planned dose) to 29 patients (39%); and Dose Level III (65% or less of the planned dose) to 32 patients (42%). Before initiation of treatment, 41 patients (55%) had a good performance status (PS greater than or equal to 80%) and 34 patients (45%) had a poor performance status (PS less than 80%) according to the Karnofsky scale. The overall response rate was 44%, including 17% complete responses. There was no significant correlation between response rates and the dose levels of chemotherapy. However, patients with a good performance status had a higher response rate (61%) compared with patients with a poor performance status (25%; p = 0.0025). The actuarial 3 year survival according to dose levels of CMF was 15%, 41% and 36% for Dose Levels I, II, and III, respectively (p = 0.34), but was 52% for patients with PS greater than or equal to 80% versus 14% for patients with PS less than 80% (p = 0.0001). These data indicate that the general condition of the patient at the time of initiation of CMF chemotherapy, as reflected by the performance status, may be of greater significance for the prediction of the ultimate treatment outcome rather than the total amount of chemotherapy delivered per se.

Adult↗

PubMedDate not supplied

Aminoglutethimide as second line endocrine therapy in advanced breast cancer.

Eighty five patients suffering from metastatic breast cancer, whose disease progressed on hormonal therapy with tamoxifen, were treated with aminoglutethimide. The overall objective response rate was 33%, with a median duration of response of 8 months. Even patients who failed to respond to tamoxifen responded to aminoglutethimide. Objective response was achieved in all metastatic sites, except for lung. Subjective improvement was observed in 75% of the patients. In spite of the fact that initial toxicity was high (70%), side effects of aminoglutethimide were transient, and treatment had to be discontinued in only 4 patients. The results of this trial indicate that aminoglutethimide is an important addition for the treatment of metastatic breast cancer, especially in patients with positive hormone receptors.

Adult↗

PubMedDate not supplied

First, second and third line chemotherapy programs in metastatic breast carcinoma.

The experience with three different chemotherapeutic regimes used as first, second and third line treatment in metastatic breast carcinoma is reported. Cyclophosphamide, Methotrexate and 5-fluorouracil (CMF) were given to 117 previously untreated patients. Objective remission was seen in 49%, including 8% with complete remission (CR) for a median duration of response lasting 16 mo. CMF plus vincristine and prednisone (CMFVP) was given to 88 patients who had failed on CMF therapy. Twenty-three percent achieved an objective remission, complete (CR) in 6% and partial (PR) in 17%, and another 28% improved I), giving a Cr+PR+I rate of 51% with remission lasting a median of six months. Finally, 23 patients who failed on CMFVP chemotherapy were given adriamycin, bleomycin, vinblastine and dimethyl-triazo-imidazole-carboxamide (ABVD) as tertiary chemotherapy; 17% achieved PR and 13% improved for a median period of nine and seven months, respectively, with a median survival of eight months for this subgroup--compared with only 4.5 months for 12 patients who progressed on this third line treatment. All three regimens were relatively well tolerated. Six patients, however, developed a fatal septic shock while leukopenic on CMFVP. Cardiac and pulmonary toxicity have not been observed. The sequential administration of chemotherapeutic regimens as reported here offers the opportunity for repeated remission in patients with active metastatic breast carcinoma and results in prolonged survival for responders.

Adult↗

PubMedDate not supplied

Treatment of locally advanced breast carcinoma with high-dose external beam supervoltage radiotherapy.

Between 1960 and 1978, 85 patients with locally advanced T3-4N0-3M0 carcinoma of the breast were treated with 5,000 to 8,000 rad of external beam supervoltage radiotherapy. Initial clinical eradication of the tumor was observed in 76 of 87 cases (87%), but the actuarial probability of local control at 6 yr was only 53%. Furthermore, the actuarial probability of disease-free survival was 25% at 5 year and 13% at 10 yr. Most of the patients eventually succumbed to metastatic breast carcinoma and the actuarial survival at 5 yr was 43% and at 10 yr, 16%. The addition of adjuvant low-dose chemotherapy, given to 13 patients, did not affect the rates of local control, survival or disease-free survival. The most common long-term complication was extensive and deforming radiation-induced fibrosis of the treated breast. The actuarial probability of 10-yr survival without a local recurrence and without severe fibrosis of the treated breast was only 17.5%. The role of adjuvant high-dose chemotherapy in the treatment of locally advanced breast carcinoma and the possible use of improved radiotherapy techniques to achieve a more effective long-term local control and a more desirable cosmetic end result are discussed.

Adult↗

PubMedDate not supplied

Immune complex-like materials in sera of patients with breast cancer: detection by complement-consumption assay.

Sera of patients with breast cancer were tested for the presence of immune complexes by a complement-consumption assay. To increase the concentration of immune complexes and thus improve the chances of their detection, sera were first ultracentrifuged and the sedimented material was assayed. Sera were considered to be positive if they consumed at least 75% of the hemolytic activity under the conditions of the test. Of the 60 patients tested, 45% were positive as compared with 13.5% positive sera among health blood bank donors. The presence of immune complexes could not be correlated with the extent of disease, the age of the patients, treatment or lack of treatment at the time of the test, or the time that had elapsed since diagnosis. In a few control tests, treatment of samples with DNase had no effect on their anticomplementary activity, whereas reduction with 2-mercaptoethanol abrogated the activity. These results strengthened the assumption that the substances binding complement were indeed immune complexes.

Adult↗

PubMedDate not supplied

Prognostic factors affecting response to aminoglutethimide in advanced breast cancer.

An analysis of 122 patients with advanced breast cancer treated with aminoglutethimide was carried out. Forty-one patients (34%) achieved a complete response or partial response (CR + PR), while 81 patients (66%) remained stable or progressed (S + P). A number of variables were analyzed for their prognostic importance in terms of response to aminoglutethimide. These variables were dominant site of metastases, disease-free survival, estrogen receptor status, age, response to prior tamoxifen, response to chemotherapy administered for metastatic disease, and dose of aminoglutethimide. The most important factors in predicting response were found to be prior response to tamoxifen and a longer disease-free survival after diagnosis.

Adult↗