Value of estrogenic recruitment before chemotherapy: first randomized trial in primary breast cancer.

PURPOSE: Several preclinical studies showed that short-term pretreatment of breast cancer cells with estrogens can increase the antitumor efficacy of different cytotoxic drugs. Some early clinical studies in patients with advanced breast cancer did seem to support these findings. Therefore, the efficacy of estrogenic recruitment followed by chemotherapy was compared with that of chemotherapy alone in a randomized phase III study in women with lymph node-positive primary breast cancer. PATIENTS AND METHODS: Three hundred twenty-eight patients with stage II/IIIA breast cancer who were younger than 66 years of age were randomly allocated to chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (FAC) or FAC plus pretreatment with ethinyl estradiol (EE(2)). FAC (500, 50, and 500 mg/m(2), respectively) was administered intravenously once every 4 weeks for four cycles. EE(2) (0.5 mg) was administered orally, both 24 hours and immediately preceding FAC chemotherapy. RESULTS: Patient and tumor characteristics and chemotherapy dosages were comparable in both treatment groups. Of 318 assessable patients, with a median follow-up of 6.8 years, 177 patients had a relapse and 127 died. No significant differences were observed between the two treatment groups with respect to relapse-free, local recurrence-free, and overall survival according to univariate and multivariate analyses adjusted for age, menopausal status, tumor size, grade, number of positive nodes, and steroid-receptor status. The power for the detection of an increase of 50% in the median relapse-free survival was 80%. CONCLUSION: Estrogenic recruitment of breast cancer cells before FAC chemotherapy did not influence the efficacy of adjuvant chemotherapy in stage II/IIIA breast cancer patients after a follow-up of 6.8 years.

Bilateral neuralgic amyotrophy induced by interferon treatment.

Neurologic side effects of interferon therapy usually consist of diffuse involvement of the central and peripheral nervous systems. We describe a patient with hairy cell leukemia who developed bilateral neuralgic amyotrophy, sacral radicular irritation, and worsening of a preexistent polyneuropathy during treatment with recombinant interferon. A sample of the patient's cerebrospinal fluid showed an increased protein content and oligoclonal banding. Several weeks after discontinuation of interferon therapy, Mees-Beau lines became evident on the patient's fingernails. The findings in this patients, as well as those recently reported by others, show that focal neurologic disturbances may be induced by interferon therapy. The clinical picture of neuralgic amyotrophy is briefly reviewed.

Lymphocyte isolation from human spleen by counterflow centrifugation employing two different flow chambers on line.

Studies on splenic lymphocytes have hitherto been performed on single cell suspensions depleted of phagocytic cells by adherence to plastic or incubation with carbonyl iron. These techniques have the disadvantages of selective cell loss, suboptimal cell purification and cell activation. This paper describes purification of splenic lymphocytes by the use of counterflow centrifugation (CFC). The method was adapted to overcome pelleting of cells in the separation chamber to form a plug at the inlet and impede adequate flow. By combining 2 different separation chambers on line in 1 rotor this problem was overcome. Of all lymphocytes recovered after CFC 88.8 +/- 1.4% were collected in 2 pooled fractions with a purity of greater than or equal to 98% and a cell viability of 95%. After CFC, 80.8 +/- 12.1% of the viable cells loaded were recovered.

Erythrocyte repopulation after allogeneic bone marrow transplantation. Analysis using erythrocyte antigens.

Blood samples from 31 of 50 consecutive patients receiving bone marrow from an HLA-identical and mixed lymphocyte culture-nonreactive sibling were investigated for the presence of donor and autologous erythrocytes. Simple serological techniques using antigenic differences between donor and recipient and a blood transfusion policy taking these differences into account made this study possible. A total of 71% of the patients had donor erythrocytes demonstrable 4 weeks after bone marrow transplantation; almost all patients did so after 2 months. Disappearance or absence of donor red cells indicated poor patient prognosis. Persistence or reappearance of autologous erythrocytes in small percentages (0.05-10%) occurred without relapse of leukemia. Reappearance in high percentage (50-100%) indicated relapse.

Ceftazidime does not enhance cyclosporin-A nephrotoxicity in febrile bone marrow transplantation patients.

Ceftazidime was used as monotherapy for 30 febrile episodes in 28 patients, who underwent allogeneic bone marrow transplantation and who were treated concomitantly with the immunosuppressive agent cyclosporin-A. Ceftazidime did not enhance the well established nephrotoxicity of cyclosporin-A as measured by serum creatinine levels or creatinine clearance. Although an increasing number of Gram-positive infections in these patients warrants vigilance, ceftazidime as initial empirical monotherapy proved to be successful in 95% of all febrile post-transplantation patients. All Gram-negative and 69% of the Gram-positive infections were cured with ceftazidime alone. The overall clinical cure rate was 72%, with microbiological clearance in 63%. This compares favourably with aminoglycoside containing schedules and avoids the aminoglycoside associated nephrotoxicity.

Phase I study of recombinant human interferon alpha-2C in patients with chemotherapy-refractory malignancies.

Twenty-two patients with advanced haemopoietic and other malignancies were treated intramuscularly with recombinant interferon-alpha 2C in a daily escalating dose. The most common side-effects were flu-like symptoms. Two patients showed severe neurotoxicity, which was completely reversible in 1 case. Doses above 30 X 10(6) IU/day were poorly tolerated and could only be achieved in a minority of the patients. Objective tumour responses were documented in malignant lymphomas, hairy cell leukaemia, and renal cell carcinoma.

Modification of stimulated lacrimal gland flow by sympathetic nerve impulses in rabbit.

This study was undertaken to determine if sympathetic nerve impulses modify lacrimal gland fluid (LGF) flow, which was continuously recorded from a cannula in the excretory duct of the lacrimal gland in rabbits anesthetized with pentobarbital sodium. The preganglionic trunk of the superior cervical ganglion was stimulated with electrical stimuli during pilocarpine-induced and reflexly induced secretion. Stimuli equal to or 6-8 times stronger than the intensity that produced maximal pupil dilation caused inhibition followed by poststimulus enhancement of LGF flow when the prestimulus LGF flow was greater than 3.0 mul/min. When the prestimulus LGF flow was less than 0.8 mul/min, the stronger stimulation enhanced LGF flow but the weaker stimulation produced inhibition followed by poststimulus enhancement of LGF flow. Although no measurements of lacrimal gland blood flow were made, the alterations in these responses, which occurred during alpha- and beta-adrenergic blockade, were consistent with the changes in sympathetically induced blood flow that occur during alpha- and beta-blockade in other organs.

Prognostic factors in adult patients with acute leukemia at first relapse.

The case histories of 252 adolescent and adult patients with acute leukemia diagnosed and treated between 1975 and 1985 are analyzed with special attention to prognostic factors determining the second complete remission (CR) rate. A first CR was achieved in 65% of cases, 60% for acute myelogenous leukemia (AML), and 75% for lymphoblastic leukemia (ALL). In 86 patients a relapse occurred (50 AML, 36 ALL), and 50% of them entered a second CR after reinduction therapy. Median survival after first relapse of these reinduction-responders was significantly prolonged in comparison to the reinduction-nonresponders for both AML (15 versus 2 months) and ALL (11 versus 3 months). Median duration of the first CR of the reinduction-responders was significantly longer than that of the second CR (13 versus 6 months). The major determinant for the probability to obtain a second CR after reinduction therapy was the duration of the first CR. The latter was significantly longer in the reinduction-responders than in the nonresponding group (13 versus 5 months). Furthermore patients younger than 40 years, and those who relapsed after ending the maintenance therapy, tended to have better chances to achieve a second CR. Rapid achievement of the first CR, and sex of the patients seemed not to be of predictive value. The authors conclude that aiming for a second CR is worthwhile in young patients who relapse after a long first CR.

Altered intracellular enzyme activity of monocytes and lymphocytes in Hodgkin's disease.

To evaluate metabolic functionality of monocytes and lymphocytes in Hodgkin's disease (HD) we studied 3 enzymes of the intermediary metabolism, G-6-PDH, PHI, ICDH, and the acid hydrolases, NAG and ACP. These enzymes were measured in purified cell fractions of 9 patients with advanced disease and 11 normal controls. The cells were isolated with cell scatter-monitored counterflow centrifugation. Enzymes were measured in the cell lysates by means of fluorimetric microassays. In the monocytes of HD patients a significantly increased G-6-PDH activity was found (P less than 0.01), indicating an enhanced activity of the hexose monophosphate shunt. The other enzymes showed no clear differences compared to normal controls. The lymphocytes of HD patients showed a significantly augmented activity of both G-6-PDH (P less than 0.001) and PHI (P less than 0.01), pointing to an increased HMPS and glycolytic activity. These findings are in support of an enhanced metabolic activity of both monocytes and lymphocytes in HD.