Cancer chemotherapy reports最新文献

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.

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.

Levels of putrescrine, spermidine, and spermine in urine were determined by means of a sensitive ion-exchange chromatographic method in patients with advanced solid tumor malignancies, in patients with diseases other than cancer, and in normal control subjects. Elevation above 2 SDS of the normal mean were found in varying number of patients in each tumor category. For those malignancies studied that involved more than 20 patients, the greatest incidences of increased excretion were 66% for spermine in patients with colon carcinoma and 50% for putrescine and spermidine in patients with bronchogenic carcinoma. The highest levels and greatest frequency of elevated polyamine levels were found in patients with Burkitt's lymphoma, and changes in clinical tumor status associated with treatment appeared to correlate well with polyamine levels in this disease. Abnormal amounts of polyamines were also excreted by some patients with diseases other than cancer, indicating that increased polyamine excretion is not restricted or specific to the neoplastic state. It was also found that the levels of polyamines were apparently not affected by the intake of meat or the diet eaten, and remained in a rather narrow excretion range for any one individual at different time intervals. This study was carried out as part of a program to determine and evaluate biologic materials present in body fluids that may be used to follow and evaluate response or progression of neoplastic disease in patients during treatment regimens. The results suggest that abnormal urinary polyamine levels may be characteristic of neoplastic growth for some patients with malignant disease. Further studies are necessary to determine if these compounds may be helpful in assessing disease status for patients with such solid tumor malignancies as colon and bronchogenic carcinoma although their potential as useful "biologic markers" appears less promising than originally anticipated.

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.