A quantitative approach to determining disease response during therapy using multiple biologic markers: application to carcinoma of the breast.

This analytical study was undertaken in an effort to develop a model for a quantitative approach to the evaluation of multiple biological marker levels in blood and urine as a means for determining tumor changes during treatment of patients with malignant disease. The potential biologic markers measured in patients with carcinoma of the breast consist of three urinary polyamines (putrescine, spermidine and spermine), three urinary nucleosides (pseudouridine, N2, N2-dimethylguanosine and 1-methylinosine), and plasma carcinoembryonic antigen (CEA). The distribution patterns of the seven markers measured pretreatment and five weeks after initiating therapy were examined by grouping the patients into the three categories of progression, stable, or regression based on their clinical response to treatment.

The pharmacokinetics of [3H]-vincristine in man.

The pharmacokinetics, metabolism, and excretion of aromatically labeled tritiated vincristine (VCR) was examined in 4 patients. Clearance of radioactivity from the blood was triphasic with half-life t1/2 values of 0.85, 7.

Distribution and excretion of (3H)vincristine in the rat and the dog.

The distribution and excretion of tritiated vincristine were studies in the rat and the dog. Biphasic curves for the disappearance of the drug from blood were found in both species, with an initial half-life of approximately 15 min and a secondary half-life of approximately 75 min. Tissue levels were high in 1 hr in the rat and declined rapidly, except in the brain where very low levels of drug were found at all times.

Alteration of methotrexate uptake in human leukemia cells by other agents.

The uptake of methotrexate (MTX) and the effect of drugs known to either inhibit or enhance MTX transport in L1210 murine leukemia were studied in man using blast cells from patients with acute myelogenous leukemia in vitro. MTX uptake was found to proceed slowly, requiring at least 160 min for cells to reach a "steady state" when extracellular MTX concentrations were 1 muM. Efflux of MTX from preloaded cells required 80 to 120 min and the nonexchangeable or tightly bound fraction was 40% of the total intracellular drug.