摘要:

The survival rate for patients with malignant gliomas is poor. We describe the results of a prospective study using concomitant chemoradiotherapy, neutron boost, and adjuvant chemotherapy for patients with malignant gliomas. Forty-two patients with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) were treated with postoperative photon radiation 45 Gy/25 fraction (fxs) with concomitant continuous intravenous infusion of 5-fluorouracil at 300 mg/m2/day×5 days and hydroxyurea 0.5 g orally every 12 hr for 6 days for 5 consecutive weeks, followed by a neutron boost of 450 N cGy/6 fxs delivered twice weekly. Adjuvant chemotherapy with procarbazine, CCNU, and vincristine (PCV) was given up to 1 year or until tumor progression. Thirty-four patients (81%) had GBM and 8 patients (19%) had AA. Sixteen patients (38%) were ineligible for the neutron boost because of large tumors or poor performance status and instead received a photon boost with concomitant chemotherapy for a total dose of 60–65 Gy to the tumor. The overall median survival is 68 weeks at a median follow-up of 203 weeks (range 166–302 weeks for the 11 patients remaining alive); 7/8 patients with AA are alive, 2 of these with progressive disease. For AA the median survival is not reached at a median follow-up of 203 weeks (range 166–302 weeks for the 7 patients alive with AA). Time to tumor progression for the 1 dead patient with AA was 35 weeks and the other 2 patients failed at 171 weeks and 179 weeks following treatment. The median survival for the 34 patients with GBM was 62 weeks; 4/34 patients with GBM are alive at 285, 238, 216, and 206 weeks. Multivariate survival analysis in the 34 patients with GBM revealed age and Karnofsky performance status as important prognostic factors. Extent of surgery and neutrons did not affect survival. Concomitant chemoradiotherapy was well tolerated by all patients. The only toxicities observed were mucositis×grade II in 3 patients (7%) and mild myelosuppression in 1 patient (2.4%). Adjuvant PCV was well tolerated. Continuous concomitant chemoradiotherapy was well tolerated by all patients with acceptable side effects. The survival rate for the patients with GBM suggests no significant impact on the prognosis for these patients. Patients with AA did well; however, the patient numbers are small.

ISSN:0735-7907    

DOI:10.3109/07357909509024906

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

A phase II trial of 5-fluorouracil (5-FU) [250450 mg/m2/day×5 days as an intravenous (IV) bolus] combined with calcium leucovorin (500 mg/m2/day×5 1/2 days by continuous IV infusion) administered on a 28-day schedule was performed in 15 patients with advanced hepatocellular carcinoma. The median age was 58 years; performance status ranged from 50 to 100%. Of 15 evaluable patients, 1 (7%) had a partial response lasting 2.4 months; 8 (53%) had stable disease with a median duration of 5.7 months; and 6 (40%) had progressive disease with a median time to progression of 2.7 months. Median survival was 3.8 months. Treatment with 5-FU and calcium leucovorin was moderately well tolerated; 9% of the treatment courses were complicated by grade 3 or 4 hematological toxicity, and 10% of the courses were complicated by grade 3 or 4 gastrointestinal toxicity. Despite the efficacy of the combination of 5-FU and leucovorin in advanced colorectal cancer, our results document the general resistance of hepatocellular carcinoma to modulated 5-FU.

ISSN:0735-7907    

DOI:10.3109/07357909509024907

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

This phase I trial evaluated a high-dose, short-term infusion of zidovudine (AZT) following oral leucovorin (LV) and bolus 5-fluorouracil (FUra). Thirteen patients with metastatic cancer received 30 cycles of therapy. Plasma monitoring demonstrated a dose-dependent increase in peak plasma levels of AZT through the range of dose levels, from 104.3±8.7μM at the 1.5 g/m2dose of AZT to 1312.6±165.9μM at the 11.0 g/m2dose. While AZT did not potentiate the usual clinical toxicities of LV plus FUra, an unexpected finding of symptomatic hypotension during the AZT infusion was the dose-limiting toxicity in this trial. One partial response was observed in a previously untreated patient with metastatic colorectal cancer. The maximal tolerated dose of AZT, 7.0 g/m2over 2 hr, is recommended for future phase II evaluation of this novel combination.

ISSN:0735-7907    

DOI:10.3109/07357909509024908

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Previous work in our laboratory showed that UFT (mixed compound of tegafur and uracil, molar ratio 1:4, respectively) caused the prolonged reduction of dTTP in L1210 leukemia cells in comparison with S-fluorouracil (S-FU). The purpose of this study was to assess the effect of UFT on cell cycle distribution and thymidylate synthase activity of a leukemia cell line as compared with 5-FU. UFT and 5-FU were orally given to BDFl mice bearing L1210 ascites tumor on day 3 after the tumor inoculation. Cell cycle distribution patterns at 24 hr after the drug administration showed a higher percentage of S phase in tumor cells treated with UFT than in those treated with 5-FU. Until 6 hr after the oral administration of the drugs, UFT inhibited the incorporation of [3H]deoxyuridine into DNA more long than 5-FU did. These results indicated that UFT has longer and stronger inhibitoiy effects on DNA replication than 5-FU in vivo under the employed experimental conditions (i.e., low and single doses of these fluorinated pyrimidines).

ISSN:0735-7907    

DOI:10.3109/07357909509024909

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Canine lymphoma is a spontaneous, naturally occurring disease that is a model for non-Hodgkin's lymphoma in humans. Chemotherapy with antineoplastics results in a high rate of remission; however, relapse and clinical drug resistance are usually seen within 8–10 months. The P-glycoprotein product of the mdr gene is thought to function as an ATP-driven membrane drug efJlux pump and appears to play an important role in tumor cell resistance. To assess the role of mdr gene products in drug resistance in canine lymphoma, membrane preparations of lymphoma cells from 31 dogs with high-or intermediate-grade lymphoma were subjected to Western blotting for detection of P-glycoprotein. In this study, one of 30 samples taken from dogs prior to receiving chemotherapy expressed detectable levels of P-glycoprotein. P-glycoprotein was also detected in biopsy samples from 3 of 8 dogs that had become resistant to chemotherapy. This pattern of expression is similar to that in human non-Hodgkin's lymphoma. These studies suggest that canine lymphoma is a useful model for studying multidrug resistance.

ISSN:0735-7907    

DOI:10.3109/07357909509024910

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

The involvement of growth factors in cell survival in the presence of anticancer drugs was investigated. Cell death was induced in the human breast cancer cell line MCF-7, by the structurally and mechanistically unrelated chemotherapeutic drugs puromycin, actinomycin D, 5-fluorouracil, cisplatin, and adriamycin. The effect of insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and insulin on cell death was evaluated by two different methods: (1) trypan blue dye exclusion test and (2) lactic dehydrogenase release into the culture medium. IGF-1 inhibited cell death induced by each of the diverse drugs in a concentration-dependent manner reaching a maximal effect at 40 ng/ml. Insulin mimicked the effect of IGF-1 only at supraphysiological concentration with an optimal effect at 10,000 ng/ml. EGF had no effect on cell death up to 100 ng/ml. Our finding that IGF-1 specifically enhanced MCF-7 cell survival in the presence of different anticancer drugs suggests the involvement of growth factors in the mechanism of drug resistance.

ISSN:0735-7907    

DOI:10.3109/07357909509024911

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

The objective of this clinical and pharmacological study was to determine whether any pretreatment parameters were associated with pharmacological or toxicity parameters after prolonged oral etoposide. Therefore, the relationships between patient characteristics and etoposide concentrations and hematological toxicity were evaluated. Sixty patients with advanced non-small cell lung cancer were treated with etoposide 50 mg/m2/day p.o. for 21 consecutive days and cisplatin 100 mg/m2i.v. on day 1. Complete blood counts and etoposide plasma concentrations were obtained weekly. Etoposide was measured by high-performance liquid chromatog-raphy. The input variables were age, gender, race, weight, weight0.66. weight0.75, height, body surface area, performance status, albumin concentration, and total etoposide dose. The outcome measures were etoposide concentration; nadir values (white blood cells, neutrophils, hemoglobin, and platelets); the absolute decrease, relative decrease, and survival fraction of blood cells; and graded toxicity. No significant correlations were found in 49 fully evaluable patients between any of the input. and outcome variables. Among the outcome variables, significant correlations were found between etoposide concentration and the logarithmic transformation of the nadir blood counts. If any of the input variables were significantly correlated to etoposide concentrations or toxicity variables, it would be possible to suggest another predictor variable besides body surface area. As long as treatment is not modified for etoposide concentrations, dosing of oral etoposide must still rely on estimates of body surface area.

ISSN:0735-7907    

DOI:10.3109/07357909509024912

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

This is the first case report ofClostridium septicumsepticemia in a patient with large granular lymphocyte leukemia. C. septicuminfection is highly associated with malignancy and causes a rapidly fatal enterocolitis among patients who are profoundly neutropenic. The need for early recognition and Combination of early antibiotic therapy and necessary surgical intervention may help to alter the fulminating nature ofC. septicuminfection.

ISSN:0735-7907    

DOI:10.3109/07357909509024913

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

A clear explanation for the high incidence of breast cancer in modern women is now possible. The risk of breast cancer rises steeply from menarche until menopause. Associated with the reproductive process, the ovary, including the corpus luteum, produces substantial amounts of estrogen and progesterone, both of which induce growth of the breast epithelium. This sex-steroid-driven breast epithelial cell proliferation increases the risk of carcinogenesis by accelerating the occurrence of somatic genetic errors. Postmenopausally, as there is little cell proliferation, the breast epithelium is more“resistant”to mutagenic effects, and breast cancer risk rises at a low rate. Unfortunately, the genetic errors accumulated during the premenopausal period are not lost following menopause, and breast cancer risk remains high. Sex-steroid antagonists, such as tamoxifen, may reduce breast cancer incidence both by blocking breast epithelial cell proliferation and by direct antitumor effects on clinically occult breast cancers. The rationale for a contraceptive designed to reduce breast cell proliferation by decreasing premenopausal sex-steroid exposure is presented.

ISSN:0735-7907    

DOI:10.3109/07357909509024914

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Very-high-dose chemotherapy produces frequent complete responses in patients with metastatic breast cancer. These responses are transient in patients with disease that had relapsed following, or was refractory to, prior conventionally dosed therapy, but when used as first chemotherapy for metastatic disease or as consolidation for patients with responding cancer, a minority achieve durable complete remissions. Improvements in supportive care, especially in hematopoietic support, have resulted in a considerable reduction in the toxicity of this therapy and may allow further intensification through the use of multiple, rapidly cycled courses.

ISSN:0735-7907    

DOI:10.3109/07357909509024915

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor