Search PubMed⌕ Search

Biomedical subjects

E Frei

Publications and source records attributed to E Frei.

At least 307 records · Page 17Linked to original sources
PubMed1978

Acute lymphoblastic leukemia: treatment.

Over the past thirty years, major progress has been achieved in the treatment of ALL. Many of the concepts, definitions, and principles of chemotherapy have and continue to be derived from studies in ALL. Major and continuing progress is ongoing for the various categories of treatment; that is, remission induction, treatment at sites of high risk for relapse (e. g., pharmacologic sanctuaries), cytoreductive therapy during complete remission, and duration of treatment. Rapid improvement in our understanding of the pathogenesis of ALL and particularly the identification of immunologic and prognostic subcategories of ALL have major therapeutic implications which are in process of being realized. Current research is focused on the development of new chemotherapeutic agents, the more rational basis for the employment of chemotherapeutic agents in combination (cytokinetic, pharmacologic, and related studies), a better definition of the host-tumor relationship particularly with respect to immunologic response and iatrogenic manipulation of such responses, and in the area of supportive care and bone marrow transplantation.

Antineoplastic Agents↗
PubMed1978

Intermittent combination chemotherapy with adriamycin for childhood acute lymphoblastic leukemia: clinical results.

One hundred thirty-seven children with previously untreated acute lymphoblastic leukemia were entered into a new program that included intermittent combination chemotherapy featuring Adriamycin. Remission induction was initially randomized to vincristine and prednisone with or without an anthracycline. All children received asparaginase consolidation and central nervous system prophylaxis with cranial irradiation and intrathecal methotrexate. There were no primary failures of CNS prophylaxis. Complications were primarily infectious. Clinical evidence of cardiotoxicity and leukoencephalopathy were not observed. The time to enter complete remission and the presence of an anterior mediastinal mass at diagnosis were found to be statistically significant adverse prognostic factors, whereas presenting age and white blood count were not. With a median follow-up of 26 mo, and using life plot analysis, 65% of the children have remianed in continuous complete remission.

Adolescent↗
PubMed1978

Hepatobiliary metabolism and excretion of adriamycin and N-trifluoroacetyladriamycin-14-valerate in the rat.

In connection with mechanism of action studies with N-trifluoroacetlyadriamycin-14-valerate (AD 32), a superior Adriamycin (ADR) analog under development in these laboratories, serial bile samples were collected from male Sprague-Dawley rats given a single i.v. dose of either ADR (4 mg/kg) or AD 32 (20 mg/kg) and were analyzed for anthracyclines by thin-layer chromatography-fluorometry and high-performance liquid chromatography. For ADR, 20% of the administered dose was accounted for at 24 hr, whereas 80% of the AD 32 dose were excreted into the bile by this time. ADR underwent little biotransformation; 80% of the 48-hr cumulative fluorescence excretion was attributable to unchanged drug, one-half the remainder was adriamycinol, and the balance was polar conjugates. In contrast, AD 32 underwent extensive metabolism to N-trifluoracetyladriamycin, N-trifluoroacetyladriamycinol, and polar conjugates, mostly glucuronides of N-trifluoroacetyladriamycin and N-trifluoroacetyladriamycinol. Based on direct and indirect evidence, ADR was not a metabolite of AD 32.

Animals↗
PubMed1978

Thymidine rescue of high-dose methotrexate in humans.

Thymidine rescue was administered following 63 courses of high-dose methotrexate in 20 patients. In the first part of this study, the methotrexate was given as a 24-hr infusion and the dose was escalated from 0.14 to 8.54 g/sq m; in the second part, methotrexate was infused to maintain a serum concentration of 15 micrometer for 30, 36, or 40 hr. Thymidine rescue was started immediately after the end of the methotrexate infusions, and consisted of 8 g/sq m/day for 3 days or until serum methotrexate was below a toxic level. Mucositis and myelosuppression were the major toxicities. Neither was dose related. Serum methotrexate levels were proportional to the logarithm of the methotrexate dose. There was a mean 6-fold increase in thymidine concentration during rescue. However, thymidine levels prior to and during rescue were not related to the incidence of subsequent toxicity. Recovery of DNA synthesis in bone marrow cells was evident by nucleoside precursor incorporation at 24 hr after the start of rescue. Two of 16 evaluable patients achieved partial responses. This study indicates that thymidine is an effective rescue agent for high-dose methotrexate in humans.

Adult↗
PubMed1978

Serial studies of cardiac function in patients receiving adriamycin.

A total of 283 adult and pediatric patients treated with drug combinations which include adriamycin (ADM) had at least one cardiac evaluation; 103 patients had two or more serial studies after a baseline evaluation. Changes in systolic time intervals, echocardiographically determined ejection fractions, and electrocardiographic voltage correlated with increasing cumulative ADM dosage. However, the incidence of congestive heart failure among these patients was less than 2%. It is estimated that 22%-31% of these patients would not have completed a cumulative dose of greater than 450 mg/m2 of ADM if the drug had been discontinued on the basis of these tests, using previously published criteria for cessation of treatment. Thus far, however, no adverse effects have been observed from the completion of planned courses of therapy. The clinical significance of serial changes in noninvasive tests is therefore uncertain. While such changes may reflect subclinical anthracycline cardiotoxicity and clinical cardiotoxicity can reliably be diagnosed, the utility of routine, serial noninvasie testing in planning conventional-dose anthracycline therapy is questionable.

Adolescent↗
PubMed1978

A therapeutic trial of maytansine.

A phase II clinical trial of maytansine, a stathmokinetic ansa macrolide, was undertaken in 70 patients. The maximally tolerated dose was 2.0 mg/m2 repeated at 21-day intervals. Gastrointestinal and central neurologic toxicity were dose limiting. No myelosuppression was noted. Two patients demonstrated transient responses. Therapeutic results from four other clinical trials were reviewed. Although additional clinical trials may be warranted in patients with bladder and small cell carcinoma, at the dose schedule reported, maytansine does not appear to possess a broad spectrum of antitumor activity. Additional clinical trials should be limited.

Adolescent↗
PubMed1977

L-dopa: selective toxicity for melanoma cells in vitro.

In a study of the effect of L-dopa, an intermediate in the biosynthesis of the pigment melanin, on the growth of human and murine melanoma cells a highly selective inhibition of growth was observed for pigmented cell lines (S91A and human melanoma) as compared to the nonpigmented control cells (amelanotic melanoma S91B, mouse fibroblast L929, and Chinese hamster ovary). There was a correlation between toxicity and the extent of incorporation of radioactively labeled L-dopa by each line.

Cell Division↗
PubMed1977

Weekly high-dose methotrexate-citrovorum factor in osteogenic sarcoma: pre-surgical treatment of primary tumor and of overt pulmonary metastases.

Vincristine-high-dose methotrexate-citrovorum factor (VCR-MTX-CF) was administered preoperatively at weekly intervals to eight patients, four with primary tumors and four with pulmonary metastases. These patients had not received prior VCR-MTX-CF treatment. A similar treatment program was administered to five patients with pulmonary metastases who had received prior VCR-MTX-CF. Among the eight patients who had not received prior VCR-MTX-CF, complete responses were obtained in three with primary tumors (this was followed by surgical excision) and two with pulmonary metastases. Partial responses occurred in two additional patients. Partial responses were also obtained in two patients who had received VCR-MTX-CF. Chemotherapy and surgery in one patient with an extremity lesion resulted in preservation of the limb and useful function. The major toxicity was anorexia and weight loss. Other side effects included stomatitis, myelosuppression, hepatitis and transient renal impairment. The weekly program was highly effective when compared to responses obtained with the tri-weekly schedule utilized in previous studies.

Bone Neoplasms↗
PubMed1977

Prognotic significance of pretreatment proliferative activity in adult acute leukemia.

A statistical analysis of the prognostic significance of eight pretreatment variables was undertaken for 71 previously untreated adult patients with acute leukemia seen at M.D. Anderson Hospital over a 5 1/2-year period. None of the patients had received any prior therapy. Nearly all of the patients (68 of the 71) were treated with 4- or 5-day courses of arabinosyl-cytosine alone or in combination with cyclophosphamide, vincristine (oncovin) and prednisone (COAP). The pretreatment variables studied were age at diagnosis, the percent labeling index of the bone marrow leukemic cells, diagnosis, the highest temperature prior to start of treatment, the marrow clot section cellularity and smear differential percent of blasts, percent absolute marrow leukemic cell infiltrate and absolute number of blasts X 10(3)/mm3 in the peripheral blood. Fifty-one patients had acute myeloblastic leukemia (AML) and 20 patients had acute lymphoblastic leukemia (ALL). Using a statistical regression model approach, the only variables found to be of significant prognostic importance with respect to the probability of complete remission for AML patients were the pretreatment percent labeling index, the age of the patient and the highest temperature prior to start of treatment. Unlike AML, the initial percent labeling index did not appear to be of prognostic significance for ALL patients. AML patients with high labeling indices (larger than or equal to 9%) and young patients in general (especially those less than 40 years old) had the best remission rates. With respect to the length of complete remission and survival for all patients, the only important variables were the pretreatment percent labeling index and the age of the patient, respectively. Once in complete remission, an initially high labeling index was an unfavorable sign with respect to length of remission, regardless of the patient's diagnosis. The results of this study are supportive of studies in experimental systems demonstrating the importance of cytokinetic factors in the administration of chemotherapy and suggest that such factors may be of clinical importance in selecting approaches to therapy.

Adult↗
PubMed1977

Rationale for combined therapy.

The presence of micrometastatic disease at the time of diagnosis is the major cause of failure in the treatment of cancer. The mechanisms, biology, and biochemistry of tumor metastases at an experimental level are being effectively studied. Potential control points and therapeutic implications are emerging. These are being employed in the construction of clinical trials involving adjuvant chemotherapy. This is part of combined modality treatment in which the best of treatment design to achieve local control (surgery and/or x-ray) is combined with systemic treatment (chemotherapy and/or immunotherapy) designed to irradicate microscopic metastases. The evolution of such studies in patients with breast cancer and osteogenic sarcoma over the past five years is presented. Disease-free survival has improved as a result of adjuvant chemotherapy for both of these diseases. While a longer follow-up will be required to determine more precisely the impact of multi-disciplinary treatment on these and other diseases, the short-time results are promising.

Animals↗
PubMed1977

Lack of effectiveness of combined 5- fluorouracil and methyl-CCNU therapy in advanced colorectal cancer.

Fifty-two patients with advanced colorectal cancer were treated with a combination of 5-Fluorouracil (FU) plus methyl-1,3-cis (2-chlorethyl)-1-nitrosourea (MeCCNU). The treatment schedule program consisted of 5-FU, 300 mg/m2 i.v. bolus, daily for 5 days, repeated at 5-week cycles. MeCCNU was administered at a dose of 150 mg/m2 orally on day 1 of the initial 5-day course of FU and repeated at 10-week intervals. Eighty-four percent (44/52) of the patients with advanced measurable disease developed progressive disease by 4 months or one and a half cycles of therapy. Only two patients had definite partial regression of tumor over the period of observation. The median survival of all patients measured from the onset of treatment was 9 months and is comparable to literature reports of untreated advanced colorectal cancer. This therapeutic trial of combined FU and MeCCNU, employing a dose-schedule distinct from but comparable to previous studies has failed to confirm the substantial response rate reported by other investigators and reinforces the need for exploring new drugs and combinations of drugs in advanced colorectal cancer. The use of sequential plasma CEA determinations as a primary monitor of therapy is discussed in relationship to clinical trials and guidelines for determining significant quantitative changes in plasma CEA levels are recommended.

Carcinoembryonic Antigen↗