Cancer treatment reports最新文献

The pharmacokinetics of thiotepa administered as a continuous infusion over 4 days have been studied in 18 patients receiving high-dose thiotepa, cyclophosphamide, and autologous bone marrow reinfusion as treatment for advanced neoplasms. Patients received cyclophosphamide at a total dose of 6 g/m2 and thiotepa at a total dose of 180-900 mg/m2 over the 4-day infusion. Samples of plasma were obtained during and following infusion, and the plasma concentration of thiotepa was determined by the method of Egorin et al. For many patients (72%), peak concentrations of plasma thiotepa were achieved during the initial 24 hours of infusion and then declined an average of 29% by the end of the 96-hour infusion. The average total systemic clearance of thiotepa was 16.7 +/- 7.4 (SD) L/m2/hour [or 420 +/- 162 (SD) ml/kg/hr]. An inverse correlation between the average total systemic clearance and the dose of thiotepa was observed (P less than 0.01).

Infants with acute lymphoblastic leukemia (ALL) have a poor prognosis. Early disease recurrence, rather than excessive toxicity and complications resulting in limitation of therapy is the major factor responsible for this disappointing outcome. The CCG-192P trial was a groupwide pilot study of the Childrens Cancer Study Group for the treatment of ALL in patients at high risk for relapse, which was defined by wbc count greater than 50 X 10(3)/microliters at diagnosis. Because of the recognized poor prognosis, all infants less than 1 year of age were entered in this study regardless of wbc count at diagnosis. Therapy included intensive induction and consolidation followed by a cyclic, sequential maintenance program. The CNS prophylaxis consisted of intrathecal chemotherapy and cranial irradiation, which was deferred until patients were greater than 1 year of age. During the period January 1982 to January 1984, 27 infants ranging in age from 2 days to 11 months who had ALL were entered in this study; 71% had wbc counts greater than 50 X 10(3)/microliters, and 23% presented with CNS leukemia. Complete remission was achieved in 93% of the patients. The median duration of remission is 17 months. With a median follow-up of 43 months, the life-table estimate of event-free survival (EFS) is 36% at 4 years. A recently reported historical control group of infants with ALL who were treated with previous Childrens Cancer Study Group protocols demonstrated a median remission duration of 8 months and an estimated EFS of only 21% at 4 years. Toxicity and therapy-related complications were not observed more frequently in infants than in older patients treated with this protocol. However, EFS of infants was significantly worse than that of patients greater than 1 year of age (P = less than 0.001). All four CNS relapses occurred in patients who had received cranial irradiation. A wbc count less than 50 X 10(3)/microliters at diagnosis demonstrated significance (P = 0.03) as a favorable prognostic indicator in this small patient sample. Although these data are preliminary, they suggest that intensive therapy is reasonably well tolerated by infants and results in prolongation of remission duration and improved EFS.

Aversions that form towards foods after their ingestion has been associated with illness are termed learned food aversions (LFA). This adverse treatment side effect has been implicated in the anorexia of cancer and can compromise the quality of patients' lives. In an attempt to block the formation or ameliorate the manifestations of this treatment sequela, a nutritionally inconsequential "scapegoat" food was presented to patients just prior to their first course of therapy. The hypothesis was that treatment-related aversions would be targeted towards the scapegoat, thereby sparing acceptable and nutrient-dense items in the patient's typical diet. LFA were observed in 55.3% of 76 patients receiving chemotherapy for different cancers. Following formation of a scapegoat aversion, the incidence of LFA was only 11.1% (two of 18) during the 6-month follow-up period. In contrast, 48.4% (15 of 31) of the patients not exposed to the scapegoat formed LFA. More than twice as many patients with treatment-related LFA had a pretreatment histology of the problem, suggesting the presence of a subgroup of high-risk patients. Strategies for improving upon the present results are discussed.

We have treated 15 patients with locally advanced or metastatic breast cancer using the synthetic 19-norsteroid gestrinone (2.5 mg orally every 3 days). All patients had assessable disease and endocrine-sensitive tumors, as defined by a previous positive response to endocrine therapy. There were no objective responses. Six patients had disease stabilization and nine had progressive disease on treatment. Seven patients were given endocrine therapy after gestrinone and three have responded. Gestrinone has no significant antitumor activity in hormone-sensitive breast cancer. This, however, does not preclude its use in benign breast disease, particularly since other agents used for benign breast disease can mask occult primary carcinoma.

The effects of the synthetic antiprogestin mifepristone (RU486) on growth of dimethylbenzanthracene (DMBA)-induced mammary tumors in female rats were investigated. Prophylactic treatment with mifepristone (10 mg/kg/day) for 3 weeks starting from the day of first DMBA injection resulted in a doubling of the average tumor latency period (81 +/- 16 days, n = 17 treated, versus 39 +/- 5 days, n = 75 controls; P less than 0.005) and was accompanied by a significant growth retardation as shown by lower body weight increments. A 3-week therapeutic treatment of rats bearing mammary tumors was performed by administration of different dosages of mifepristone (2.5, 10, or 40 mg/kg/day) or megestrol acetate (2.5 or 10 mg/kg/day), with the luteinizing hormone-releasing hormone agonist buserelin (40 micrograms/kg/day), buserelin plus mifepristone (10 mg/kg/day), or by ovariectomy. The effects of treatment on tumor load, pituitary, adrenal and reproductive organ weights, steroid receptor contents of mammary tumors, and blood plasma hormone concentrations were investigated. Mifepristone and megestrol acetate treatment gave rise to inhibition of mammary tumor growth with all dosages studied, in which mifepristone was more potent than megestrol acetate (80%-90% vs 40% inhibition, P less than 0.01). In contrast, buserelin treatment and ovariectomy resulted not only in inhibition, but in tumor remission by about 50%. Combined treatment with buserelin and mifepristone gave the same tumor remission as resulted from ovariectomy or single treatment with buserelin. Estradiol-stimulated growth of the human mammary cancer MCF-7 cells in culture was fully abolished by mifepristone (3.6 X 10(-8) M) or tamoxifen (4 X 10(-8) M), whereas growth of MCF-7 cells under control incubation was not affected by either agent. Therefore, a direct inhibition of the growth of rat mammary tumor cells by mifepristone appears likely. Based on the effects of mifepristone on plasma hormone levels (increased: luteinizing hormone, estradiol, progesterone; unchanged: follicle-stimulating hormone, adrenocorticotropic hormone, corticosterone), organ weights (increased: pituitary, ovaries, uterus; unchanged: adrenals) and steroid receptor contents of mammary tumors (decreased: estrogen receptor and progesterone receptor contents), the main mechanism of action is probably a direct antiprogestational effect at the level of the mammary tumor cells through occupancy of the progesterone receptor.