Cancer chemotherapy reports最新文献

Tissue concentration of 3H-actinomycin D have been determined in the rat, monkey, and dog after an iv dose of 0.6 mg/m2 body surface area. The drug-tissue half-life was determined for various tissues of the rat, monkey, and dog. A mean drug-tissue half-life of 47 hours was calculated for the tissues of the dog. Exceptions were the testis and brain. Significant concentrations of 3H-actinomycin D failed to accumulate in the brain. Although testis drug concentrations were lower than most other tissues evaluated, the drug-tissue half-life was significantly greater than that of other tissues. In all species studied 3H-actinomycin D was rapidly depleted from serum after iv dosage, with concomitant accumulation of drug in the tissues. 3H-actinomycin D was excreted via the biliary and urinary routes in all species studied. No metabolites of 3H-actinomycin D were detected in the bile or urine of the rat, monkey, or dog with the methods employed. When expressed on a body weight basis, body surface area doses were more than threefold greater in the rat than in the dog. However, the average ratio of concentration X time values (rat C X T/dog C X T) for 11 different tissues of the rat and dog was only 1.3. The results strongly suggest that an equivalent dose of actinomycin D, with dosage based on a body surface area basis, results in nearly equal tissue-drug exposure for most tissues in various mammalian species.

Children with acute lymphoblastic leukemia who had experienced only one relapse were reinduced into remission using a 6-week induction course of prednisone and vincristine. One hundred fifty-one children who achieved a second complete marrow remission were randomly assigned to one of three cyclophosphamide treatment groups for maintanence. Forty-one children received standard-dose cyclophosphamide (3 mg/kg/day), 55 received intermittent high-dose cyclophosphamide (10 mg/kg/day for 4 days out of 14), and 55 received a combination of oral cyclophosphamide (3 mg/kg/day) plus cytosine arabinoside (3 mg/kg/week im). The standard-dose cyclophosphamide regimen resulted in a remission maintenance time of 109 days and was the least toxic of the three maintenance regimens. Giving cyclophosphamide on an intermittent high-dose schedule or combining it with cytosine arabinoside did not increase the remission maintanence time (105 days).

Two dose schedules of guanazole were used in this phase I clinical study: intermittent prolonged 5-day infusion and intermittent iv bolus twice weekly. Ninety-seven treatment observations were analyzed for toxic effects resulting from the prolonged infusion and 42 from the twice-weekly bolus schedule. The main toxic effect was bone marrow suppressions, the frequency and severity of which were intensified by prior chemotherapy or radiotherapy and repetition of guanazole therapy. The leukocyte count was affected more than the platelet count. Partial responses were observed in four patients: two with lung carcinoma, one with prostate carcinoma, and one with melanoma. Further phase II clinical studies of guanazole are indicated.

Nineteen patients with various solid tumors were treated with Corynebacterium parvum for 10 consecutive days at doses ranging from 0.5 to 6 mg/m2. Major toxic effects included rigors and cyanosis, hypertension, headache, nausea, and vomiting. Toxicity was maximal during the first 3 days of treatment and decreased or even disappeared when, on subsequent days, increasing doses of the vaccine were given. Objective tumor regressions were observed in four patients.

The toxic effects of cytembena in beagle dogs and rhesus monkeys were investigated with the drug given as single or daily iv injections in doses ranging from 12.5 to 200 mg/kg/day to dogs and 6.25 to 50 mg/kg/day to monkeys. Renal tubular damage was a major drug- and dose-related finding in both species and was clinically indicated by an accompanying uremia, elevated serum creatinine, and proteinuria. In the kidney, the primary lesion was cellular necrosis and desquamation of the distal tubular epithelium in animals given the lowest toxic doses. More severe but similar histologic changes produced by this drug were further characterized by single dose studies in mice which showed renal mitochondrial swelling and disruption plus generalized cell swelling as progressive, subcellular developments which were well established 24 hours after treatment. Cellular regeneration in the renal tubular epithelium was found in dogs and monkeys retained 6 weeks for observation after treatment, although functional recovery was inconsistent. A toxic effect to lymphoid tissue was an additional finding which is described.