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  • 2020-2023
  • 2000-2004  (22)
  • Chemotherapy  (22)
  • 1
    Electronic Resource
    Electronic Resource
    Effect of 5-(phenylselenenyl)acyclouridine, an inhibitor of uridine phosphorylase, on plasma concentration of uridine released from 2′,3′,5′-tri-O-acetyluridine, a prodrug of uridine: relevance to uridine rescue in chemotherapy (2000)
    Springer
    Cancer chemotherapy and pharmacology 46 (2000), S. 235-240 
    Details
    ISSN: 1432-0843
    Keywords: Key words 5-(Phenylselenenyl)acyclouridine ; Uridine phosphorylase ; Inhibitor ; Triacetyluridine ; Chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: The purpose of this investigation was to study the effects of combining oral 5-(phenylselenenyl)acyclouridine (PSAU) with 2′,3′,5′-tri-O-acetyluridine (TAU) on the levels of plasma uridine in mice. PSAU is a new lipophilic and potent inhibitor of uridine phosphorylase (UrdPase, EC 2.4.2.3), the enzyme responsible for uridine catabolism. PSAU has 100% oral bioavailability and is a powerful enhancer of the bioavailability of oral uridine. TAU is a prodrug of uridine and a far superior source of uridine than uridine itself. Methods: Oral TAU was administered to mice alone or with PSAU. The plasma levels of uridine and its catabolites as well as PSAU were measured using HPLC and pharmacokinetic analysis was performed. Results: Oral administration of 2000 mg/kg TAU increased plasma uridine by over 250-fold with an area under the curve (AUC) of 754 μmol · h/l. Coadministration of PSAU at 30 and 120 mg/kg with TAU further improved the bioavailability of plasma uridine resulting from the administration of TAU alone by 1.7- and 3.9-fold, respectively, and reduced the Cmax and AUC of plasma uracil. Conclusion: The exceptional effectiveness of PSAU plus TAU in elevating and sustaining a high plasma uridine concentration could be useful in the management of medical disorders that are remedied by administration of uridine, as well as the rescue or protection from host toxicities of various chemotherapeutic pyrimidine analogues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800000138
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  • 2
    Electronic Resource
    Electronic Resource
    Modulation of plasma uridine concentration by 5-(phenylselenenyl)acyclouridine, an inhibitor of uridine phosphorylase: relevance to chemotherapy (2000)
    Springer
    Cancer chemotherapy and pharmacology 45 (2000), S. 351-361 
    Details
    ISSN: 1432-0843
    Keywords: Key words 5-(Phenylselenenyl)acyclouridine ; Uridine phosphorylase ; Chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: The purpose of this investigation was to evaluate the efficacy of oral 5-(phenylselenenyl)-acyclouridine (PSAU) in increasing endogenous plasma uridine concentration as well as its ability to improve the bioavailability of oral uridine. PSAU is a new potent and specific inhibitor of uridine phosphorylase (UrdPase, EC 2.4.2.3), the enzyme responsible for uridine catabolism. This compound was designed as a lipophilic inhibitor in order to facilitate its access to the liver and intestine, the main organs involved in uridine catabolism. Methods: Oral PSAU was administered orally to mice alone or with uridine. The plasma levels of PSAU as well as uridine and its catabolites were measured using high-performance liquid chromatography and pharmacokinetic analysis was performed. Results: PSAU has an oral bioavailability of 100% and no PSAU metabolites were detected. PSAU has no apparent toxicity at high doses. Oral administration of PSAU at 30 and 120 mg/kg increased baseline concentration of endogenous plasma uridine (2.6 ± 0.7 μM) by 3.2- and 8.7-fold, respectively, and remained three- and six-fold higher, respectively, than the controls for over 8 h. PSAU, however, did not alter the concentration of endogenous plasma uracil. Co-administration of PSAU with uridine elevated the concentration of plasma uridine over that resulting from the administration of either alone, and reduced the peak plasma concentration (C max) and area under the curve (AUC) of plasma uracil. Co-administration of PSAU at 30 mg/kg and 120 mg/kg improved the low bioavailability of oral uridine (7.7%) administered at 1320 mg/kg by 4.8- and 4.2-fold, respectively, and reduced the AUC of plasma uracil from 1421 to 787 μmol/h · l and 273 μmol/h · l, respectively. Similar results were observed when PSAU was co-administered with lower doses of uridine. Oral PSAU at 30 mg/kg and 120 mg/kg improved the bioavailability of oral 330 mg/kg uridine by 5.2- and 8.9-fold, and that of oral 660 mg/kg uridine by 6.4- and 9.0-fold, respectively. However, the reduction in the AUC values of plasma uracil was less dramatic than that seen when the high dose of 1320 mg/kg uridine was used. Conclusion: The effectiveness of the PSAU plus uridine combination in elevating and sustaining high plasma uridine concentration may be useful to rescue or protect from host toxicity of various chemotherapeutic pyrimidine analogs as well as in the management of medical disorders that are remedied by administration of uridine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800051002
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  • 3
    Electronic Resource
    Electronic Resource
    Successful treatment with paclitaxel of a patient with metastatic extra-adrenal pheochromocytoma (paraganglioma) (2000)
    Springer
    Cancer chemotherapy and pharmacology 45 (2000), S. 428-431 
    Details
    ISSN: 1432-0843
    Keywords: Key words Extra-adrenal pheochromocytoma ; Chemotherapy ; Paclitaxel ; Paraganglioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This case report describes the history of a patient with an aggressive course of a metastatic extra-adrenal pheochromocytoma (paraganglioma) who received different combination chemotherapy regimens with no or short-lasting clinical benefit. However, during treatment with single-agent paclitaxel, there was a significant clinical improvement, a partial biochemical response and a minor roentgenologic response, which was sustained for 1 year. In this report we present this case and also review the literature on the chemotherapy used for this rare disease over the past 15 years. To enable the activity of paclitaxel against this neoplasm to be determined, more patients need to be treated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800051013
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  • 4
    Electronic Resource
    Electronic Resource
    Further evidence for oxidant-induced vascular endothelial growth factor up-regulation in the bronchoalveolar lavage fluid of lung cancer patients undergoing radio-chemotherapy (2000)
    Springer
    Journal of cancer research and clinical oncology 126 (2000), S. 352-356 
    Details
    ISSN: 1432-1335
    Keywords: Key words Lung cancer ; Oxidative stress ; Reactive oxygen species ; Radiotherapy ; Chemotherapy ; Vascular endothelial growth factor ; Bronchoalveolar lavage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Vascular endothelial growth factor (VEGF) is a potent inducer of physiological and neoplastic blood vessel growth. Moreover, in vitro studies have demonstrated that VEGF can be up-regulated by conditions associated with the generation of free radicals and reactive oxygen species. In a previous study we reported on strongly increased VEGF concentrations in the bronchoalveolar lavage fluid (BALF) of patients with lung cancer under therapy. In this study we aimed to reveal whether this increase was due to the therapy-associated intrapulmonary oxidative burden. Patients and methods: A total of 103 BALF samples from 94 patients with lung cancer (82 patients with non-small-cell lung cancer, 12 patients with small-cell lung cancer) were studied at different times before, during or after cancer treatment. VEGF levels in the lavage fluid and ratios of oxidised methionine in proteins of epithelial lining fluid (ELF) were determined. Results: As reported previously, strongly increased VEGF levels in the ELF were observed in patients undergoing chemotherapy when radiotherapy had been administered before. Increased levels of oxidised methionine indicated that these patients suffered from severe pulmonary oxidative stress that was significantly less in patients undergoing only chemotherapy. Similarly, VEGF concentrations in the ELF were significantly elevated in cancer patients at the time of diagnosis, but the oxidised methionine levels did not reveal significant oxidant/antioxidant imbalances in these patients. Conclusion: Systemic chemotherapy is associated with oxidative stress in vivo, which is more pronounced if patients are additionally treated with radiation. VEGF levels in the ELF are increased by this condition as well as by the activity of the tumour itself.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050355
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  • 5
    Electronic Resource
    Electronic Resource
    A role for preirradiation PCV chemotherapy for oligodendroglial brain tumors (2000)
    Springer
    Journal of neurology 247 (2000), S. 297-302 
    Details
    ISSN: 1432-1459
    Keywords: Key words Oligodendroglioma ; Oligoastrocytoma ; PCV ; Chemotherapy ; Brain tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Oligodendroglial tumors have been identified as a subgroup of glial neoplasms with a distinctly better response to chemotherapy and overall survival than purely astrocytic gliomas. Here we report our experience with adjuvant postirradiation and preirradiation chemotherapy using procarbazine, lomustine, and vincristine (PCV) in 27 patients with WHO grade II or III oligodendroglioma or oligoastrocytoma. The efficacy of chemotherapy was assessed according to the Macdonald response criteria (complete response, CR; partial response, PR; stable disease, SD; progressive disease, PD) and progression-free survival intervals by computed tomography or magnetic resonance imaging. First, we confirm that PCV salvage therapy for patients progressing after radiotherapy is highly effective (n = 11, 1 CR, 5 PR, 5 SD; median progression-free survival has not yet been reached, but is longer than 18 months). Second, 3 patients who received radiotherapy plus PCV as first-line therapy achieved CR and 2 achieved SD, and all 5 are progression-free with a median follow-up of 12 months. Third, given these encouraging results, 11 patients received postoperative preirradiation PCV chemotherapy and were given radiotherapy only upon progression. Preirradiation PCV chemotherapy was also effective (2 CR, 3 PR, 6 SD; median progression-free survival has not been yet reached, but is longer than 14 months). Patients with anaplastic oligoastrocytomas were as likely to respond to PCV chemotherapy, as were patients with anaplastic oligodendroglioma. Three patients who had previously responded to PCV were successfully treated with a second course of PCV upon recurrence. PCV chemotherapy was also effective in patients with leptomeningeal spread of oligodendrogliomas. A randomized prospective trial is required to compare the effectiveness and neurotoxicity of first-line PCV chemotherapy followed by radiotherapy to the traditional reverse sequence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050587
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  • 6
    Electronic Resource
    Electronic Resource
    Isolated meningeal chloroma (granulocytic sarcoma) – a case report and review of the literature (2000)
    Springer
    Annals of hematology 79 (2000), S. 459-462 
    Details
    ISSN: 1432-0584
    Keywords: Key words Chloroma ; Acute myeloblastic leukemia ; Chemotherapy ; Autologous stem cell transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Isolated chloromas (granulocytic sarcomas) are rare tumors, most of them progressing to acute myeloblastic leukemia within months. There are still no conclusive treatment strategies for this entity; however, early antileukemic chemotherapy seems to lower the probability of developing systemic disease and prolong survival. We report on a patient with isolated meningeal chloroma, primarily misdiagnosed as a high-grade Non-Hodgkin's lymphoma. Two cycles of antileukemic induction chemotherapy were administered, followed by local irradiation and intensified consolidation therapy with autologous stem cell transplantation. After 20 months, he is still in complete remission.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770000165
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  • 7
    Electronic Resource
    Electronic Resource
    Staphylococcal pyomyositis in a patient with non-Hodgkin's lymphoma (2000)
    Springer
    Annals of hematology 79 (2000), S. 279-282 
    Details
    ISSN: 1432-0584
    Keywords: Key words Pyomyositis ; Non-Hodgkin's lymphoma ; Chemotherapy ; Splenectomy ; Abscess
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Pyomyositis is a rare disease, encountered mainly in tropical climates. The diagnosis of this entity is difficult, if not misdiagnosed, because of its rarity and its subacute presentation. We report of a 42-year-old man, in whom pyomyositis developed while he was receiving the standard chemotherapy for T-cell non-Hodgkin's lymphoma (NHL). Three months following splenectomy, multiple abscesses occurred in the muscles of both thighs while the patient was receiving the third course of the CHOP regimen. A purulent exudate was aspirated from the abscesses under computed tomographic guidance. Coagulase-positive Staphylococcus aureus was cultured in the aspirate. Pyomyositis was completely resolved following the surgical drainage and the antistaphylococcal antibiotic treatment. This patient has shown that immunosuppression due to splenectomy, NHL, and chemotherapy, especially when using steroids, could be risk factors for pyomyositis in nontropical or semitropical countries.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050594
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  • 8
    Electronic Resource
    Electronic Resource
    How much does it cost to preserve a larynx? (2000)
    Springer
    European archives of oto-rhino-laryngology and head & neck 257 (2000), S. 72-76 
    Details
    ISSN: 1434-4726
    Keywords: Key words Laryngeal carcinoma ; Laryngectomy ; Organ preservation ; Chemotherapy ; Treatment costs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Various studies report an increase in costs when induction chemotherapy is included in the treatment of advanced laryngeal cancer, but to our knowledge no studies have yet compared the economic costs of total laryngectomy versus induction chemotherapy in the treatment of advanced laryngeal cancer. We have conducted a retrospective study comparing the costs of treatment and survival in 96 patients with a T3N0-1 glottic carcinoma. Findings showed that the average cost per patient in the group of patients treated by total laryngectomy with or without postoperative radiotherapy was 5,853 Eur, while that for the group of patients who began treatment with induction chemotherapy was 6,452 Eur. The adjusted 5-year survival for patients treated with total laryngectomy with or without postoperative radiotherapy was 80%, and 72% for patients who began treatment with induction chemotherapy. Sixteen of the 35 patients (46%) receiving induction chemotherapy were spared laryngectomy. The use of induction chemotherapy in the treatment of patients with advanced laryngeal carcinomas involved an increase in cost of 600 Eur in relation to treatment with total laryngectomy and postoperative radiotherapy. However, from an economic point of view, we consider induction chemotherapy to be an important consideration in an organ-preservation strategy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007513
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  • 9
    Electronic Resource
    Electronic Resource
    Rhabdoid tumors of the central nervous system (2000)
    Springer
    Child's nervous system 16 (2000), S. 228-234 
    Details
    ISSN: 1433-0350
    Keywords: Key words Brain tumor ; Rhabdoid tumor ; Chemotherapy ; Radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rhabdoid tumors of the central nervous system are rare malignancies with a still almost uniformly fatal outcome. There is still no proven curative therapy available. We report our experience with nine patients with central nervous system rhabdoid tumors. Gross complete surgical removal of the tumor was achieved in six patients. Seven patients received intensive chemotherapy. Four of these were treated in addition with both neuroaxis radiotherapy and a local boost directed to the tumor region, while two patients received local radiotherapy only. The therapy was reasonably well tolerated in most cases. Despite the aggressive therapy, eight of the nine patients died from progressive tumor disease, and one patient died from hemorrhagic brain stem lesions of unknown etiology. The mean survival time was 10 months after diagnosis. Conventional treatment, although aggressive, cannot change the fatal prognosis of central nervous system rhabdoid tumors. As these neoplasms are so rare, a coordinated register would probably be a good idea, offering a means of learning more about the tumor’s biology and possible strategies of treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003810050503
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  • 10
    Electronic Resource
    Electronic Resource
    Reduction of cyclophosphamide bioactivation by thioTEPA: critical sequence-dependency in high-dose chemotherapy regimens (2000)
    Springer
    Cancer chemotherapy and pharmacology 46 (2000), S. 119-127 
    Details
    ISSN: 1432-0843
    Keywords: Key words ThioTEPA ; Cyclophosphamide ; Pharmacokinetics ; Drug-drug interaction ; Chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Cyclophosphamide and thioTEPA are frequently used simultaneously in high-dose chemotherapy regimens. During a pharmacokinetic study of 31 courses in 20 patients of cyclophosphamide and its activated metabolite 4-hydroxycyclophosphamide given in the combination cyclophosphamide–thioTEPA–carboplatin, a sharp decrease in 4-hydroxycyclophosphamide concentration was observed immediately after the start of the thioTEPA infusion. A drug-drug interaction was suspected. This putative interaction was investigated in this study. Methods: Possible sequence dependency, due to inhibition of the formation of 4-hydroxycyclophosphamide by thioTEPA, was investigated by altering the sequence of infusion in three patients (four courses) receiving high-dose chemotherapy with cyclophosphamide (1000 or 1500 mg/m2 per day), thioTEPA (80 or 120 mg/m2 per day) and carboplatin (265 or 400 mg/m2 per day) in short infusions for four consecutive days. The pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide were established. Possible inhibition of the metabolism of cyclophosphamide and thioTEPA was investigated in human microsomes. Results: A striking sequence dependency of the pharmacokinetics of 4-hydroxycyclophosphamide was observed. Administration of thioTEPA 1 h prior to cyclophosphamide resulted in decreased Cmax (−62%) and AUC (−26%) values of 4-hydroxycyclophosphamide compared to those of thioTEPA administered 1 h after cyclophosphamide. In human microsomes an inhibition of the conversion of cyclophosphamide to 4-hydroxycyclophosphamide by thioTEPA was observed at clinically relevant concentrations with an IC50 of 23 μM. No inhibition of the formation of TEPA by cyclophosphamide was observed. Conclusions: ThioTEPA strongly inhibits the bioactivation of cyclophosphamide and this may decrease both efficacy and toxicity. Our results seriously question the practice of the simultaneous continuous infusion of cyclophosphamide and thioTEPA and suggest that the sequencing and scheduling of these two agents in high-dose chemotherapy regimens may be of critical importance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800000132
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