The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform

Claudius Rudin - One of the best experts on this subject based on the ideXlab platform.

  • Cyclophosphamide thalidomide and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem cell transplantation mrc myeloma ix randomized trial results
    Haematologica, 2012
    Co-Authors: Gareth J Morgan, Gordon Cook, Faith E Davies, W M Gregory, Sue E Bell, A J Szubert, Sylvia Feyler, Peter R E Johnson, Claudius Rudin, Mark T Drayson
    Abstract:

    Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. Design and Methods Oral Cyclophosphamide, thalidomide, and dexamethasone was compared with infusional Cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with Cyclophosphamide-thalidomide-dexamethasone (n=555) versus Cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P <0.0001. The complete response rates were 13.0% with Cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone ( P =0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P =0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to Cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with Cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for Cyclophosphamide-thalidomide-dexamethasone over Cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with Cyclophosphamide-vincristine-doxorubicin-dexamethasone, Cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The Cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior in terms of survival outcomes to the standard infusional regimen of Cyclophosphamide-vincristine-doxorubicin-dexamethasone. Based on its oral administration and the reduced incidence of infection and cytopenia, Cyclophosphamide-thalidomide-dexa-methasone may be considered an effective induction therapy option for patients with newly diagnosed multiple myeloma. (ISRCTN: 68454111)

  • Cyclophosphamide thalidomide and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem cell transplantation mrc myeloma ix randomized trial results
    Haematologica, 2012
    Co-Authors: Gareth J Morgan, Gordon Cook, Faith E Davies, W M Gregory, Sue E Bell, A J Szubert, Sylvia Feyler, Peter R E Johnson, Nuria Navarro Coy, Claudius Rudin
    Abstract:

    Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation.Design and Methods Oral Cyclophosphamide, thalidomide, and dexamethasone was compared with infusional Cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma.Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with Cyclophosphamide-thalidomide-dexamethasone (n=555) versus Cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P

Gareth J Morgan - One of the best experts on this subject based on the ideXlab platform.

  • Cyclophosphamide thalidomide and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem cell transplantation mrc myeloma ix randomized trial results
    Haematologica, 2012
    Co-Authors: Gareth J Morgan, Gordon Cook, Faith E Davies, W M Gregory, Sue E Bell, A J Szubert, Sylvia Feyler, Peter R E Johnson, Claudius Rudin, Mark T Drayson
    Abstract:

    Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. Design and Methods Oral Cyclophosphamide, thalidomide, and dexamethasone was compared with infusional Cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with Cyclophosphamide-thalidomide-dexamethasone (n=555) versus Cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P <0.0001. The complete response rates were 13.0% with Cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone ( P =0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P =0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to Cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with Cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for Cyclophosphamide-thalidomide-dexamethasone over Cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with Cyclophosphamide-vincristine-doxorubicin-dexamethasone, Cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The Cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior in terms of survival outcomes to the standard infusional regimen of Cyclophosphamide-vincristine-doxorubicin-dexamethasone. Based on its oral administration and the reduced incidence of infection and cytopenia, Cyclophosphamide-thalidomide-dexa-methasone may be considered an effective induction therapy option for patients with newly diagnosed multiple myeloma. (ISRCTN: 68454111)

  • Cyclophosphamide thalidomide and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem cell transplantation mrc myeloma ix randomized trial results
    Haematologica, 2012
    Co-Authors: Gareth J Morgan, Gordon Cook, Faith E Davies, W M Gregory, Sue E Bell, A J Szubert, Sylvia Feyler, Peter R E Johnson, Nuria Navarro Coy, Claudius Rudin
    Abstract:

    Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation.Design and Methods Oral Cyclophosphamide, thalidomide, and dexamethasone was compared with infusional Cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma.Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with Cyclophosphamide-thalidomide-dexamethasone (n=555) versus Cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P

Jos H. Beijnen - One of the best experts on this subject based on the ideXlab platform.

  • simultaneous quantification of Cyclophosphamide and its active metabolite 4 hydroxyCyclophosphamide in human plasma by high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry lc ms ms
    Journal of Chromatography B, 2007
    Co-Authors: Corine Ekhart, Abadi Gebretensae, Hilde Rosing, Jos H. Beijnen
    Abstract:

    Abstract Cyclophosphamide is a cytotoxic prodrug with a very narrow therapeutic index. To study the clinical pharmacology of Cyclophosphamide in a large cohort of patients a previously published method for the simultaneous quantitative determination of Cyclophosphamide and 4-hydroxyCyclophosphamide in human plasma using liquid chromatography tandem mass spectrometry (LC–MS/MS) was optimized. Addition of an isotopically labelled internal standard and adaptation of the gradient resulted in a fast, robust and sensitive assay. Because 4-hydroxyCyclophosphamide is not stable in plasma, the compound is derivatized with semicarbazide immediately after sample collection. Sample preparation was carried out by protein precipitation with methanol–acetonitrile (1:1, v/v), containing isotopically labelled Cyclophosphamide and hexamethylphosphoramide as internal standards. The LC separation was performed on a Zorbax Extend C18 column (150 mm × 2.1 mm ID, particle size 5 μm) with 1 mM ammonium hydroxide in water–acetonitrile (90:10, v/v) as the starting gradient, at a flow-rate of 0.40 mL/min with a total run time of 6 min. The lower limit of quantification (LLQ, using a 100 μL sample volume) was 200 ng/mL and the linear dynamic range extended to 40,000 ng/mL for Cyclophosphamide and 50–5000 ng/mL for 4-hydroxyCyclophosphamide. Accuracies as well as precisions were lower than 20% at the LLQ concentration and lower than 15% for all other concentrations. This method has been successfully applied in our institute to support ongoing studies into the pharmacokinetics and pharmacogenetics of Cyclophosphamide.

  • Reduction of Cyclophosphamide bioactivation by thioTEPA: critical sequence-dependency in high-dose chemotherapy regimens
    Cancer Chemotherapy and Pharmacology, 2000
    Co-Authors: Alwin D. R. Huitema, Sjoerd Rodenhuis, Matthijs M. Tibben, Thomas Kerbusch, Jos H. Beijnen
    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.

Mark T Drayson - One of the best experts on this subject based on the ideXlab platform.

  • Cyclophosphamide thalidomide and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem cell transplantation mrc myeloma ix randomized trial results
    Haematologica, 2012
    Co-Authors: Gareth J Morgan, Gordon Cook, Faith E Davies, W M Gregory, Sue E Bell, A J Szubert, Sylvia Feyler, Peter R E Johnson, Claudius Rudin, Mark T Drayson
    Abstract:

    Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. Design and Methods Oral Cyclophosphamide, thalidomide, and dexamethasone was compared with infusional Cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with Cyclophosphamide-thalidomide-dexamethasone (n=555) versus Cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P <0.0001. The complete response rates were 13.0% with Cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone ( P =0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P =0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to Cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with Cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for Cyclophosphamide-thalidomide-dexamethasone over Cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with Cyclophosphamide-vincristine-doxorubicin-dexamethasone, Cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The Cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior in terms of survival outcomes to the standard infusional regimen of Cyclophosphamide-vincristine-doxorubicin-dexamethasone. Based on its oral administration and the reduced incidence of infection and cytopenia, Cyclophosphamide-thalidomide-dexa-methasone may be considered an effective induction therapy option for patients with newly diagnosed multiple myeloma. (ISRCTN: 68454111)

Sue E Bell - One of the best experts on this subject based on the ideXlab platform.

  • Cyclophosphamide thalidomide and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem cell transplantation mrc myeloma ix randomized trial results
    Haematologica, 2012
    Co-Authors: Gareth J Morgan, Gordon Cook, Faith E Davies, W M Gregory, Sue E Bell, A J Szubert, Sylvia Feyler, Peter R E Johnson, Claudius Rudin, Mark T Drayson
    Abstract:

    Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. Design and Methods Oral Cyclophosphamide, thalidomide, and dexamethasone was compared with infusional Cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with Cyclophosphamide-thalidomide-dexamethasone (n=555) versus Cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P <0.0001. The complete response rates were 13.0% with Cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone ( P =0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P =0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to Cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with Cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for Cyclophosphamide-thalidomide-dexamethasone over Cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with Cyclophosphamide-vincristine-doxorubicin-dexamethasone, Cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The Cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior in terms of survival outcomes to the standard infusional regimen of Cyclophosphamide-vincristine-doxorubicin-dexamethasone. Based on its oral administration and the reduced incidence of infection and cytopenia, Cyclophosphamide-thalidomide-dexa-methasone may be considered an effective induction therapy option for patients with newly diagnosed multiple myeloma. (ISRCTN: 68454111)

  • Cyclophosphamide thalidomide and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem cell transplantation mrc myeloma ix randomized trial results
    Haematologica, 2012
    Co-Authors: Gareth J Morgan, Gordon Cook, Faith E Davies, W M Gregory, Sue E Bell, A J Szubert, Sylvia Feyler, Peter R E Johnson, Nuria Navarro Coy, Claudius Rudin
    Abstract:

    Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation.Design and Methods Oral Cyclophosphamide, thalidomide, and dexamethasone was compared with infusional Cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma.Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with Cyclophosphamide-thalidomide-dexamethasone (n=555) versus Cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P