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Biomedical subjects

E Frei

Publications and source records attributed to E Frei.

At least 325 records · Page 18Linked to original sources
PubMed1977

Adriamycin plus alkylating agents in the treatment of metastatic breast cancer.

A randomized trial of Adriamycin (A) in combination with melphalan (M), (MA therapy), and in combination with M plus cyclophosphamide (C) (MAC therapy), was initiated in 40 evaluable patients with metastatic breast cancer. Twenty-two patients demonstrated an objective response to therapy: 9/20 to the MA regimen, and 13/20 to the MAC regimen. For the 22 responders, median duration of response is not yet achieved for either complete or partial responders, at 10 and 9 months, respectively. The addition of the two alkylating agents to Adriamycin was superior to the single alkylating agent addition, both in total response rate and in completeness of response. Maintenance therapy, after achieving the maximum cumulative dose of Adriamycin, was provided by cyclophosphamide plus methotrexate and 5-fluorouracil (CMF). In 19 patients completing induction and entering maintenance therapy, only one relapse has developed with maximun follow-up at 15 months.

Adult↗
PubMed1977

Clinical and cytokinetic aspects of remission induction of childhood acute lymphoblastic leukemia (ALL): addition of an anthracycline to vincristine and prednisone.

Fifty-six untreated patients with childhood with acute lymphoblastic leukemia (ALL) were randomized to receive one of three remission induction regimens: vincristine and prednisone (VP), vincristine, prednisone and daunorubicin (VPD), or vincristine, prednisone and adriamycin (VPA). The complete remission rate was similar for all three groups. Although the anthracycline regimens caused somewhat more rapid leukemic cell reduction than the VP only group, this difference was not significant. Labeling index reduction between study days 1 and 5 was significantly greater (p less than 0.001) with an anthracycline than for the VP group, but there was no difference between the two anthracyclines. Granulocytopenia during induction was significantly increased (p less than 0.05) in both the VPD and VPA groups as compared with VP alone. A significantly higher rate of infectious morbidity (p less than 0.01) was associated with the addition of either anthracycline, but to date no significant differences in remission duration or survival have been observed. The addition of anthracyclines to VP for remission induction in childhood ALL has theoretical advantages, but may be undesirable because of increased morbidity.

Child, Preschool↗
PubMed1977

Weekly methotrexate-calcium leucovorin rescue: effect of alkalinization on nephrotoxicity; pharmacokinetics in the CNS; and use in CNS non-Hodgkin's lymphoma.

Urinary alkalinization with oral sodium bicarbonate has decreased the incidence of acute nephrotoxicity and subsequent myelotoxicity in 18 adults receiving high-dose methotrexate with calcium leucovorin rescue (MTX-LCV) weekly in doses of 1-7.5 g/m2. Close monitoring of 24-hour serum creatinine and MTX levels can predict patients at risk for serious toxicity. By a prompt (24-36 hours) increase in the LCV dose rate, hematologic and biochemical evidence of myelosuppression has been prevented. Kinetic parameters in serum and lumbar cerebrospinal fluid (CSF) were studied in two patients following iv injection of 3 and 7.5 g/m2 respectively. Lumbar CSF MTX concentrations greater than 1 muM are achieved. The half-life of MTX in the CSF (11.95 hours) is twice as long as the serum half-life. In the presence of carcinomatous meningitis, further delay in the clearance of MTX from the CSF was seen. With weekly MTX-LCV, there have been four objective responses in six patients with non-Hodgkin's lymphoma in CNS relapse, including complete regression in two. It is suggested that therapeutic concentrations can be achieved in the central nervous system following MTX-LCV.

Adult↗
PubMed1977

High-dose methotrexate with citrovorum factor in osteogenic sarcoma--progress report II.

Vincristine (VCR), high-dose methotrexate (MTX), and citrovorum factor (CF) were administered to 12 patients with classic osteogenic sarcoma with local control. Seven patients (58%) are free of pulmonary metastases for 2+-31/2+ years. With a second adjuvant program incorporating adriamycin (VCR, MTX, CF, and adriamycin), 16 of 20 patients are free of pulmonary metastases for 6+-18+ months. Five patients who developed pulmonary metastases were rendered free of disease by surgical resection. The VCR, MTX, and CF program was also administered at weekly intervals to eight patients with pulmonary metastases or unresected primary lesions. Two complete and one partial response were obtained in four patients with pulmonary metastases and three complete and one partial response were obtained in patients with primary lesions. This program was also administered in combination with radiation therapy to four patients who relapsed on conventional VCR, MTX, CF, and adriamycin therapy following surgical resection of pulmonary metastases. They remain free of recurrent disease for 2+-14+ months. There was no alteration in the incidence of toxicity when compared to earlier investigations. The results indicate that the VCR, MTX, and CF program has had a major impact on the management of osteogenic sarcoma.

Doxorubicin↗
PubMed1977

Combination chemotherapy of advanced non-Hodgkin lymphoma with bleomycin, adriamycin, cyclophosphamide, vincristine, and prednisone (BACOP).

Seventy-three patients with advanced non-Hodgkin lymphoma were treated with bleomycin, Adriamycin, cyclophosphamide, vincristine (Oncovin) and prednisone (BACOP), administered intensively during a 7-wk induction course followed by intermittent cycles every 3 wk for a total of 28 wk. The objective response in 44 evaluable nonleukemic patients with diffuse histology was 86%, with 66% achieving a complete remission (CR), varying from 80% for diffuse poorly differentiated lymphocytic (DPDL) to 56% for diffuse histiocytic (DH) lymphoma. In patients with nodular histology 89% (8/9) achieved a CR with a projected 75% of patiients in CR at 14 mo. Median follow-up from time of CR for nodular histology was 17 mo. The projected median duration of CR in diffuse histology was 14 mo. with median survival 14 mo. Patients with a partial response survived a median of 7 mo, compared to 3 mo for nonresponders. Of 29 patients with diffuse histology, 17 (59%) have remained disease free for 5-34 mo with a median follow-up of 12 mo. Survival beyond 20 mo has been projected for 42% of patients with diffuse histology (58% with DPDL and 32% with DH). The central nervous system (CNS) was involved in a total of 11/44 (25%) patients with diffuse histology, including 5 with primary CNS relapse. BACOP resulted in a higher CR rate and longer survival than a previous three-drug program (COP), especially in patients with diffuse histology.

Adolescent↗
PubMed1977

Selective incorporation of L-3,4-dihydroxyphenylalanine by S-91 Cloudman melanoma in vitro.

The incorporation of precursors of the biopigment melanin into melanotic and amelanotic S-91 Cloudman melanoma, mouse fibroblast L-929, and Chinese hamster ovary cells was studied. Tyrosine did not selectively accumulate in pigmented cells compared to that in nonpigmented control cells. Inhibition of protein synthesis with cycloheximide provided an estimate of the partition of tyrosine between protein (95%) and pigment biosynthesis (5%). L-3,4-Dihydroxyphenylalanine, a more proximal precursor of melanin, was selectively incorporated into pigmented cells up to 60 times that of control lines. alpha-Melanocyte-stimulating hormone and theophylline, agents that enhance pigmentation, further increased the incorporation of L-3,4-dihydroxyphenylalanine into melanocytic cells. A unique property of melanoma cells thereby has been defined that may permit a selective chemotherapeutic and diagnostic approach.

Cells, Cultured↗
PubMed1977

The prevention of methotrexate toxicity by thymidine infusions in humans.

Continuous i.v. thymidine (TdR) was given to 12 patients with metastatic cancer in an attempt to prevent methotrexate (MTX) toxicity. MTX was infused in 27 courses with progressive dose increase from 80 mg/sq m for 24 hr to 6 g/sq m for 72 hr. TdR at 8 g/sq m/day was infused concurrently and continued 24 to 48 hr beyond MTX infusion. The median pretreatment serum TdR level was 0.19 micron. With TdR infusion, the median level was 1.5 micronM. Serum TdR fell with a half-time of 8 to 10 min after a pulse dose or cessation of infusion. Spinal fluid TdR equaled serum TdR levels after 2 hr of infusion. Less than 2% of administered TdR appeared in urine. MTX serum levels were proportional to dose infused, ranging from 80 to 100 micronM with 2 g/sq m/day. The half-time for MTX clearance from serum was 4 to 8 hr. Spinal fluid MTX reached equilibrium at 3 to 12% of serum levels by 4 hr. Bone marrow dysfunction during MTX infusion was prevented by TdR as determined by labeling indices and cytofluorographic analyses. Toxicity was not seen in patients with normal MTX clearance using 48-hr infusions of MTX where TdR was continued for an additional 48 hr after the MTX infusion had ended. However, 3 of 6 courses of MTX at 6 g/sq m over 72 hr led to toxicity. Toxicity was reversible in 2 patients, 1 of whom was retreated with a similar dose duration of MTX without toxicity when TdR was continued beyond the end of the MTX infusion for 48 hr instead of the usual 24 hr. The 3rd patient with toxicity died of progressive disease and thrombocytopenia 19 days after treatment. No TdR-related toxicity or unusual MTX toxicity was detected. Antitumor effects were noted in 4 patients. TdR offers significant protection against MTX toxicity and deserves further clinical study.

Adult↗
PubMed1976

Multidisciplinary treatment for macrometastatic osteogenic sarcoma.

Using a co-ordinated multidisciplinary approach with surgery, radiation therapy, and chemotherapy, 14 out of 21 patients with metastases from osteogenic sarcoma were rendered free of disease for over two to over 18 months. Most patients had pulmonary metastases, two had bony metastases, and one had metastases in the iliac nodes. As part of this multidisciplinary approach weekly high-dose methotrexate was given and caused tumour regression in seven out of 15 patients. After all clinical evidence of disease had been removed high-dose methotrexate was administered every two to three weeks as maintenance treatment. To assess the efficacy of treatment the results were compared with those in a historical control group of 82 consecutive patients who developed pulmonary or other metastases. The results in the study group were significantly better. This experience may be similar to that in Wilms's tumour, where actinomycin D has increased the cure rate when administered as adjuvant therapy after treatment of localised or overt metastatic disease.

Adolescent↗
PubMed1976

New multiple-agent chemotherapy (B-DOPA) for advanced Hodgkin's disease.

B-DOPA (Bleomycin (B), D-imidazole carboxamide (D), Oncovin (O), Prednisone (P), Adriamycin (A) is a program developed for the treatment of Hodgkin's disease resistant to MOPP therapy. Twenty unselected patients were treated by the following dose schedule: B, 4 mg/m2 days 2 and 5; D, 150 mg/m2 days 1 to 5; O (vincristine), 1.5 mg/m2 days 1 and 5; P, 40 mg/m2 days 1 to 6; A, 60 mg/m2 day 1. Each course, was repeated at 3 to 4 week intervals to maximum adriamycin dose of 450 mg/m2. All patients had received prior MOPP therapy and six had received prior radiotherapy. Fifteen of the 20 patients entered into the study were evaluable for response. There were nine (60%) complete responders and three (20%) partial responders. The median duration of complete remission was 14+ months with six of nine patients remaining in remission to a maximum of 21 months. The median survival of the nonresponders was 3 months. B-DOPA is an effective combination chemotherapy regimen for advanced Hodgkin's disease in patients who have previously received MOPP treatment, including patients who are refractory to MOPP therapy. The B-DOPA program or modifications thereof, may be integrated into primary treatment programs for advanced Hodgkin's disease.

Adult↗
PubMed1976

Development of an effective treatment program for childhood acute lymphocytic leukemia: a preliminary report.

The development of an effective therapeutic regimen for acute lymphocytic leukemia (ALL) of childhood is described. By careful surveillance of toxicity and efficacy, positive modifications of treatment strategy were achieved without resorting to classically randomized trails. Teh resultant protocol utilizes vincristine-prednisone induction followed by asparaginase consolidation, intensive intermittent combination maintenance chemotherapy with adriamycin as a major component, and cranial radiotherapy plus intrathecal methotrexate for central nervous system prophylaxis. Preliminary analysis suggests that this regimen may result in prolonged continuous complete remission in at least 80% of children with ALL.

Adolescent↗
PubMed1976

Cell cycle synchronization of human lymphoid cells in vitro by 2,3-dihydro-1h-imidazo[1,2-b]pyrazole.

2,3-Dihydro-1H-imidazo[1,2-b]pyrazole (IMPY), a DNA synthesis-inhibitory drug, reversibly arrests growth of human lymphoblasts in vitro. DNA distribution histograms of cultures exposed to 0.5 to 2.0 mM IMPY show accumulation of cells with G1-early S DNA content. On reincubation in fresh medium, cell cycle traverse is resumed by the blocked cells in a synchronized manner. Maximum incorporation of [H3]thymidine into DNA (174 to 220% of control) and labeling indexes (72 to 86%) are seen after 4 hr of incubation, and a major increase in cell number is seen between the 9th and 13th hr. DNA distribution histograms of cells reincubated in fresh medium (after double block), show an initial increase in the number od cells with S-G2-M DNA content and a corresponding decrease in the number of G1-early S cells. After 4 hr of reincubation, a gradual increase in the number of G1-early S cells was seen as the earlier blocked cells completed cell cycle traverse and mitosis. Cells exposed to 2.0 mM IMPY took approximately 2 hr longer to traverse than did cells exposed to 0.5 mM IMPY.

Cell Division↗
PubMed1976

Effect of adriamycin on the cell cycle traverse and kinetics of cultured human lymphoblasts.

Exposure of cultured human lymphoblasts to adriamycin (ADM) (0.1 mug/ml for 24 hr or 0.5 mug/ml for 1 hr) leads to an accumulation of cells with the DNA content of late S and G2. Higher concentrations of ADM (0.5 to 10 mug/ml) inhibit cell cycle traverse. Effect of ADM on cell cycle traverse, cell growth, and incorporation of labeled precursors into DNA is dependent on drug concentration and length of exposure to ADM. Synchronized cells in G1 or G2 part of the cell cycle are less sensitive to ADM than cells in S phase. Similarly, plateau-phase cells are less sensitive to ADM than cells from log-phase cultures.

Cell Division↗
PubMed1976

Differences in cellular uptake and cytofluorescence of adriamycin and N-trifluoroacetyladriamycin-14-valerate.

Adriamycin-specific fluorescence appears slowly in living cells and is localized in nuclei and chromosomes. N-Trifluoroacetyladriamycin-14-valerate, a recently synthesized adriamycin analog, differs from the parent anthracycline in the rapid appearance of its fluorescence in the cytoplasm of living cells and the lack of any fluorescent binding to nuclei and chromosomes.

Cell Line↗