摘要:

ABSTRACTThe effect of adriamycin (ADR), vincristine (VCR), mitoxantrone (MTN) and cis-platin (PtCl) at acidic pH on the incorporation of 3H-thymidine (3H-TdR) was studied in vitro on P388 murine leukemia cells. The incorporation was inhibited at low pH by the four drugs used. In order to induce acidosis in tumor bearing mice, 6 g/kg glucose was administered intraperitoneally. The lowest pH that could be obtained was 6.8 two hours after glucose administration. The drugs ADR, VCR, MTN and PtCl administered to tumor-bearing mice 2 h following induction of acidosis resulted in significant increase in the life span of the tumor bearing mice.

ISSN:1043-0733    

DOI:10.1089/sct.1991.7.1

年代:1991

数据来源: MAL

摘要:

ABSTRACTAutoradiographic analysis of the intratumor location of radioiodinated Mu-9 anti-CSAp antibody within 7 days of administration reveals a restricted distribution within 3-6 cell layers surrounding tumor vessels. Within 7-14 days after suboptimal radioantibody treatment (∼3000 rads), tumor vessel morphology and physiology are altered. Vessel number is reduced by 60-70%, vessel diameter is reduced, and remaining vessels are surrounded by fibrotic tissue. Vascular volume (vv) is reduced by 75%, blood flow rate (BF) is reduced 65%, and vascular permeability (VP) to an lgG is reduced by 60%. The change in vv is reversible by day 35 but BP and VP remain suppressed. Normal tissue (liver and lung) vasculature experience only small pertubations in physiology. These functional changes in tumor vessels reduce the magnitude of accretion of a second dose of radioantibody in tumor but not in normal tissu

ISSN:1043-0733    

DOI:10.1089/sct.1991.7.9

年代:1991

数据来源: MAL

摘要:

ABSTRACTSince continuous exposure increases the cytotoxicity of 5-Fluorouracil, this agent is now commonly administered by 4-5 day continuous infusions. However Phase I studies have suggested that infusion of doses up to 450 mg/m2/day for at least 28 days may be possible. In the present study 12 patients with advanced head and neck cancer were treated with continuous infusion 5-Fluorouracil at starting doses of 400-450 mg/m2/day for 28 days followed by a 14 day rest period. Patients received a median of 2.5 cycles over 10 weeks for a median total 5-Fluorouracil dose of 12,700 mg/m2. One patient achieved Partial Response. Significant stomatitis (Grade II or greater) was seen more frequently than predicted from Phase I studies (8/12 patients) and was the most common cause for dose reduction. Diarrhea, emesis, palmar/plantar syndrome and skin rash were also noted. No significant myelosuppression was seen. Extremely large amounts of 5-Fluorouracil can be delivered to head and neck cancer patients by extended infusion. However due to the high frequency of stomatitis in this population, lower starting doses than those used in this study may be required.

ISSN:1043-0733    

DOI:10.1089/sct.1991.7.17

年代:1991

数据来源: MAL

ISSN:1043-0733    

DOI:10.1089/sct.1991.7.23

年代:1991

数据来源: MAL

摘要:

SUMMARYFifteen patients with progressive primary malignant or metastatic brain tumors were treated on a clinical and pharmacokinetic study with intracarotid cisplatin and bleomycin. Toxicity was tolerable and consisted mainly of nausea and vomiting. Neurologic toxicity included focal seizures (1), leukoencephalopathy (1), and motor weakness (1). Five patients had improvement in CT scans and four patients had stabilization of disease. Recommended dosage for future clinical trials are cisplatin 60 mg/m2and bleomycin 100 units. Pharmacokinetics of intracarotid cisplatin revealed the jugular vein concentration was twice the peripheral vein level at the end of infusion.Cisplatin is a drug which has demonstratedin vitroactivity against malignant gliomas (1). Clinical trials with intravenous administration of cisplatin has shown definite, although limited antitumor activity against primary brain tumors (2,3,4) and metastatic brain tumors (5,6). To enhance its antitumor effect, cisplatin has been administered by the intracarotid route (7,8,9). The results appear encouraging, but neurological and ophthalmological toxicity may occur (8). In our initial study with intracarotid cisplatin, 35 patients with malignant brain tumors (23 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation ± chemotherapy were treated. Of 20 evaluable patients with primary tumors, 6 responded to therapy and 5 had stable disease. Five of 10 evaluable patients with brain metastases responded and 2 had stable disease. For responding primary brain tumor patients the median time to progression was 33 weeks. The recommended dose for intracarotid cisplatin was 60-75 mg/m2administered every 3-4 weeks (7,8). Higher cisplatin doses produced more central neurological toxicity.There is limited data on the central nervous system pharmacology of cisplatin. Certain studies have found only low platinum concentrations in normal brain and cerebrospinal fluid (10, 11) but higher concentrations are found in brain tumors after intravenous or intracarotid administration (10). As part of our studies with intracarotid cisplatin alone or when combined with other drugs, we have investigated the pharmacology of intracarotid cisplatin. Bleomycin was used with cisplatin for several reasons. Intracerebral bleomycin therapy has improved survival in a rat brain tumor model (9) gliosarcoma (12). In addition, bleomycin has shown antitumor activity in tissue cultures of human glioma cell lines (13). In thisin vitrostudy, growth inhibition occurred in 7 of 15 brain tumors at bleomycin concentration of 10 mU/ml. Bleomycin has been administered postoperatively and intravenously in patients with brain tumors with some response (14). We report here our results of a pilot clinical and pharmacokinetic trial of intracarotid cisplatin and bleomycin

ISSN:1043-0733    

DOI:10.1089/sct.1991.7.29

年代:1991

数据来源: MAL

ISSN:1043-0733    

DOI:10.1089/sct.1991.7.37

年代:1991

数据来源: MAL

ISSN:1043-0733    

DOI:10.1089/sct.1991.7.38

年代:1991

数据来源: MAL