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Biomedical subjects

J B Block

Publications and source records attributed to J B Block.

At least 37 records · Page 2Linked to original sources
PubMed1984

Abnormal deoxyuridine suppression as a rapid predictor for antimetabolite chemosensitivity: correlation with in vitro tests of growth inhibition.

The deoxyuridine (dU) suppression test, which estimates the activity of the de novo pathway to DNA synthesis from dU, was evaluated as a predictor of antimetabolite growth inhibition. Observations of growth inhibition were made using flask cell culture and soft agar clonogenic assay and correlated with results of the rapidly performed dU suppression test in human (SK-L7) leukemia cells, in methotrexate-sensitive and -resistant murine (L1210) leukemia cells, and in human tumor explants. The concentration of methotrexate resulting in a positive dU suppression test was closely correlated with the methotrexate concentrations required for growth inhibition in flask and soft agar culture systems. The fact that the dU suppression test can be rapidly interpreted in 4 hours compared to the longer period required for clonogenic assay suggests that further evaluation of this procedure as a rapid predictor for clinical antimetabolite response is warranted.

Animals↗
PubMed1984

Influence of hydrazine sulfate on abnormal carbohydrate metabolism in cancer patients with weight loss.

Thirty-eight patients with advanced cancer and weight loss were tested in a prospectively randomized, double-blind, placebo-controlled trial to evaluate the influence of hydrazine sulfate on carbohydrate metabolism in cancer cachexia. All patients had an initial 3-day inpatient metabolic evaluation including: standard 5-hr p.o. glucose tolerance test, hormone studies, and total glucose production by infusion of [6-3H]glucose. After 30 days of treatment with capsules containing either placebo or hydrazine sulfate in a 60-mg, 3 times/day dosage, inpatient evaluation was repeated. A total of 62 metabolic inpatient evaluations were performed. The pretreatment characteristics of age, sex, prior therapy experience, nutritional parameters and tumor types were comparable in placebo and hydrazine treatment groups. On initial evaluation, abnormal glucose tolerance and increased glucose production were frequently seen. Serial assessment of glucose tolerance showed no improvement after 30 days of placebo treatment. However, the glucose tolerance was significantly improved in patients receiving 30 days of hydrazine sulfate [2-hr glucose; initial 169 +/- 24 (S.E.) mg/dl versus final 128 +/- 12 mg/dl; p less than 0.05]. In addition, the rate of total glucose production was significantly decreased after 30 days of hydrazine sulfate compared to placebo treatment (2.46 mg/kg/min versus 3.07 mg/kg/min, respectively; p less than 0.05). Toxic effects of hydrazine sulfate were minimal. Our results suggest that hydrazine sulfate can influence the abnormal carbohydrate metabolism associated with weight loss in patients with cancer.

Adult↗
PubMed1983

Doxorubicin and CCNU with or without vincristine in patients with advanced refractory breast cancer. A randomized trial.

Thirty-five patients with advanced breast cancer refractory to initial chemotherapy were randomized to receive two-drug doxorubicin-CCNU or three-drug doxorubicin-CCNU-vincristine (VCR) treatment. Doxorubicin (25-40 mg/m2) and VCR (1.4 mg/m2) were given intravenously every 21 days; CCNU (65-90 mg/m2) was given orally every 42 days. Patients with liver or bone marrow metastases initially received the lower range doses. All patients failed prior chemotherapy with cyclophosphamide and 5-FU with or without methotrexate and prednisone; 67% received prior hormonal therapy. Pretreatment patient characteristics were comparable in both groups. Objective responses (greater than 50% reduction in tumor size) were seen in 7 of 18 patients (39%) on the VCR containing arm and in 8 of 17 patients (46%) on the doxorubicin-CCNU arm. Survival was not improved by VCR addition with overall survival on the doxorubicin-CCNU arm, approximately 10% greater at all intervals (median 9.1 versus 7.0 months; not statistically significant). However, neurotoxicity was significantly greater in the VCR arm (36% versus 0%; P less than 0.05). In advanced breast cancer, no benefit to VCR addition was seen in prior randomized studies of first-line combinations where VCR was the treatment variable. Such results, combined with our experience with VCR in a salvage regimen, question the value of VCR addition to combination regimens in advanced breast cancer.

Breast Neoplasms↗
PubMed1982

Doxorubicin cytotoxicity enhanced by local anesthetics in a human melanoma cell line.

Local anesthetics may influence cell membrane structure and permeability. An established human melanoma cell line (SHG) derived from malignant ascites was used to evaluate the growth-inhibitory effects of local anesthetics (procaine and lidocaine) as well as of doxorubicin at incubation temperatures of 37.5 degrees C and 40 degrees C. In this system, procaine and lidocaine inhibited growth at 0.82 mg/ml and doxorubicin inhibited growth at 28 ng/ml. Noninhibitory concentrations of procaine (0.64 mg/ml) when combined with noninhibitory concentrations of doxorubicin (10 ng/ml) resulted in marked growth inhibition. Incubating temperatures of 40 degrees C enhanced all effects of procaine and doxorubicin on cell growth. These results suggest that clinically achievable concentrations of local anesthetics enhance doxorubicin cytotoxicity.

Cell Line↗
PubMed1982

Clinical and pharmacokinetic effects of combined warfarin and 5-flourouracil in advanced colon cancer.

Twenty-five patients with advanced measurable adenocarcinoma of the colon were treated with 5-fluorouracil (FUra), 15 to 20 mg/kg/week i.v., plus warfarin p.o. at a dosage which maintains therapeutic levels of anticoagulation. Sixty-four % of patients achieved either objective response (20%) or stable disease (44%). Overall median survival was 19.2 months. Three patients (all with intraluminal lesions) developed gastrointestinal blood loss requiring transfusion and discontinuation of anticoagulation. The interaction between warfarin and FUra as measured by plasma levels was investigated in seven rabbits and three patients. Plasma samples were obtained for 2 hr after FUra administration, both before and after anticoagulation with warfarin. FUra was measured by gas chromatography, and warfarin was assayed using a thin-layer chromatographic fluorescence method. In rabbits, prolongation of FUra plasma t1/2 was seen with high (0.6 mg/kg/hr) but not low (0.025 mg/kg/hr) rates of warfarin infusion. In patients, FUra t1/2 was not changed by therapeutic warfarin anticoagulation. Thus, (a) plasma clearance interaction between FUra and warfarin does not occur in patients receiving therapeutic levels of anticoagulation; (b) FUra and warfarin anticoagulation can be safely given and frequently result in stable disease status for patients with advanced colon cancer. Further trials of this combination are warranted in adenocarcinoma of the colon.

Adenocarcinoma↗
PubMed1979

Chemotherapy of unresectable or recurrent metastatic malignant melanomas: an update.

Satisfactory chemotherapeutic management of malignant melanomas in advanced stages must await development of more active agents and combinations of them than are presently available. The development of entirely new means of treatment by hormones, heat, and adjuvants like amphotericin B may improve the efficacy of currently available agents.

Amphotericin B↗
PubMed1979

Status report of 376 mycosis fungoides patients at 4 years: Mycosis Fungoides Cooperative Group.

The frequency and prognostic importance of various characteristics of patients registered by the Mycosis Fungoides Cooperative Group between November 1974 and December 1977 are reported. Variables which were considered include demographic and historical factors, symptoms, extent of disease, and other physical findings. A staging system which is based on the extent of skin involvement and the number of nodal sites clinically involved is described. Finally, a description of therapeutic results to date for patients randomized into Mycosis Fungoides Cooperative Group protocols is presented.

Adult↗
PubMed1978

Phase II clinical trial with high-dose methotrexate therapy and citrovorum factor rescue.

One hundred and thirty-four patients with advanced malignant disease were treated with 496 infusions of high-dose methotrexate (HD-MTX) followed by citrovorum factor rescue. Most patients had failed to respond to previous combination chemotherapy. The overall response rate was 29% with 33 partial responses and six complete responses observed in patients with a variety of tumors. Plasma MTX levels were monitored in all patients during each course of therapy in order to identify those patients with delayed plasma MTX clearance. Patients with abnormally slow rates of plasma MTX decay received escalated doses of citrovorum factor rescue in order to prevent drug-induced toxicity. In general, during this study HD-MTX was well-tolerated. Because serious toxicity was neither frequent, severe, nor unpredictable, its use was not limited. HD-MTX should now be evaluated in well-designed controlled clinical trials to compare its antitumor activity to that of conventional- or standard-dose MTX regimens in diseases where HD therapy appears to have efficacy.

Adolescent↗
PubMed1977

Pharmacokinetics of high-dose methotrexate with citrovorum factor rescue.

The methotrexate (MTX)-plasma concentrations of 172 high-dose infusions over the range of 50-200 mg/kg were measured over the 72-hour period following the beginning of infusion. Pharmacokinetic analysis shows that a biexponential function adequately describes the plasma decay for all doses. The distribution of plasma clearances over the patient population at a given dose has been characterized by a biexponential clearance function and associated time-dependent variance. It is found that when each of the plasma clearance functions are scaled by their respective dose, the 1 SD bands about the resulting unit dose curves overlap throughout their time ranges and are therefore insignificantly different from one another. Thus, the plasma clearance over the 50-200-mg/kg range may be represented by a single dose-scalable biexponential model with half-lives of 1.8 +/- 0.1 and 8.4 +/- 0.5 hours. For a given maximum allowable plasma-MTX level (eg, 10(-5) M at 24 hours), the variance of the clearance distribution is shown to predict the expected fraction of patients who will require intensified rescue. Urinary clearance has been determined at 104 +/- 8 ml/minute over the dose range of 50-300 mg/kg and only 60% of the MTX was excreted in the urine by 72 hours.

Adolescent↗
PubMed1976

High dose methotrexate therapy of solid tumors: observations relating to clinical toxicity.

In clinical studies performed during 111 infusions of high dose methotrexate (MTX) we have evolved a clinical and laboratory protocol which permits such therapy without prohibitive risk to the patient. The plasma MTX data obtained indicate that pharmacokinetic disposition is dose related during these infusions and that such data are useful in identifying patients at risk from serious toxicity.

Adolescent↗
PubMed1976

Local delayed cutaneous hypersensitivity reactions in breast cancer patients with and without removal of axillary lymph nodes.

Fifty-five patients were sensitized to dinitrochlorobenzene (DNCB). Two weeks later they were challenged. The minimal concentration yielding 2+ reactivity and one dilution above and below were then applied to the anterior chest wall on both the operated and nonoperated sides. Using multinomial chi-square statistical analysis, we found that the operated and nonoperated sides evidenced equal reactivity. Futhermore, the absence of axillary lymph nodes did not diminish the reactivity in the operated area. These data support the contention that maintenance of local cellular immunity, as assessed by DNCB skin test reactivity, is systemic and counters the argument that regional lymphadenectomy impairs local and/or systemic cellular immunity.

Animals↗