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Intravenous Cyclophosphamide (intravenous + cyclophosphamide)
Selected AbstractsIntravenous cyclophosphamide is the drug of choice for steroid dependent nephrotic syndromePEDIATRICS INTERNATIONAL, Issue 1 2003ZELAL B AbstractBackground: Steroid dependency is a major problem seen after therapy for idiopathic nephrotic syndrome in childhood. Although there is consensus about the usage of cyclophosphamide (CYC) in frequent relapsers, there is still a controversy concerning its usage in steroid-dependent nephrotic syndrome (SDNS). Methods: In the present study, nineteen children with SDNS were treated with CYC: ten via the intravenous (i.v.) route, and nine via the oral route. Remission was then maintained with prednisolone. Oral CYC therapy consisted of CYC at a dose of 2 mg/kg per day for 12 weeks. Intravenous (i.v.) CYC therapy consisted of CYC 500 mg/m2 per month (with intravenous 3500 cc/m2 per 24 h one-third saline hydration) for 6 months. Results: The cumulative dose of CYC was 168 mg/kg in the oral group and 132 mg/kg in the IV group. Daily oral CYC dose was 1.96~0.31 mg/kg, whereas i.v. CYC dose was 0.73~0.03 mg/kg. Long-term complications and side-effects such as alopecia, infection and hemorrhagic cystitis were not observed in the i.v. CYC treated group. In the long term, the dosage of prednisolone that held remission after CYC, the annualized relapse rates and the subsequent relapse time were significantly better in the i.v. CYC group, and the number of patients in remission for 2 years was significantly higher in the i.v. treated group (P<0.05). Conclusion: In SDNS, i.v. CYC has a long lasting effect with lower annualized relapse rates and longer subsequent relapse time with a lower steroid dosage required to maintain remission than oral CYC. The results of the present study showed the safety of the i.v. route, and it is the preferable treatment in noncompliant patients for its long lasting remission and simple and inexpensive follow up. [source] Cyclophosphamide pulse therapy followed by azathioprine or methotrexate induces long-term remission in patients with steroid-refractory Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2006C. SCHMIDT Summary Background In patients with steroid-refractory Crohn's disease, the therapeutic goal is to achieve both rapid remission and maintenance of clinical response. Aim To evaluate the long-term benefit in patients treated with cyclophosphamide pulse therapy and azathioprine or methotrexate, a combination shown to be effective in a recent pilot study. Methods Sixteen patients with acute steroid-refractory Crohn's disease participated in a prospective open-labelled uncontrolled pilot study between December 1998 and June 2003. All had a median number of 4 monthly pulses of intravenous cyclophosphamide (750 mg) and were followed until relapse of the disease. Results Thirteen of 16 patients (81%) achieved remission within 8 weeks after two pulses of cyclophosphamide in combination with azathioprine or methotrexate, with a Crohn's Disease Activity Index decrease from 294 to 111 (median). Remission sustained for 19 months (median, range: 1,45). Moreover, eight patients with pyoderma gangrenosum and erythema nodosum who responded to cyclophosphamide have maintained their remission for up to 30 months. Conclusions In steroid refractory patients with Crohn's disease, cyclophosphamide is highly effective to induce remission. This uncontrolled study indicates that cyclophosphamide-induced remission is long-lasting under standard immunosuppressive therapy. [source] Plasma pharmacokinetics of high-dose oral busulfan in children and adults undergoing bone marrow transplantationPEDIATRIC TRANSPLANTATION, Issue 2003Bruce Bostrom Abstract: We have analyzed the plasma pharmacokinetics of busulfan in 272 patients receiving high-dose oral busulfan and intravenous cyclophosphamide in conjunction with allogeneic or autologous bone marrow transplantation. The patients ranged in age from 2 months to 59 yr (mean 10, median 12 yr) and had the following diagnoses: thalassemia or sickle cell anemia (n = 74); leukemia or myelodysplasia (n = 112); inborn errors of metabolism (n = 41) or immunodeficiency (n = 45). Plasma specimens were collected following the first dose for each patient which ranged from 1 to 4 mg/kg (mean ± SD, 1.21 ± 0.41, median 1.15). Busulfan was quantitated using ultraviolet absorbance detection after derivatization and HPLC separation. Pharmacokinetic parameters were derived by modeling the raw data to fit first-order single compartment kinetics. The kinetic parameters showed wide interpatient variability independent of age and diagnosis. There was a statistically significant correlation of age with the following parameters: area under the curve (AUC); maximal concentration; minimum concentration; clearance; volume of distribution and absorption half-time. The coefficients of determination (i.e. correlation coefficient squared) were low ranging from 0.04 to 0.12 implying only a small part (i.e. 4,12%) of the variance was explained by age. Although busulfan pharmacokinetics are age-related most of the variability is not explained by age or diagnosis. [source] High-dose cyclophosphamide versus monthly intravenous cyclophosphamide for systemic lupus erythematosus: A prospective randomized trial,ARTHRITIS & RHEUMATISM, Issue 5 2010Michelle Petri Objective Monthly intravenous (IV) cyclophosphamide for 6 months has been the standard induction regimen for lupus nephritis, followed by a maintenance regimen of quarterly infusions for 2 years. We undertook this study to compare the efficacy and safety of the standard regimen versus a high-dose IV cyclophosphamide regimen. Methods We performed a prospective randomized trial comparing monthly IV cyclophosphamide at 750 mg/m2 body surface area for 6 months followed by quarterly IV cyclophosphamide for 2 years (traditional treatment) against high-dose IV cyclophosphamide (50 mg/kg daily for 4 days) (high-dose treatment). Entry criteria included renal lupus, neurologic lupus, or other organ system involvement with moderate-to-severe activity. Results Fifty-one patients were randomized; 3 withdrew before treatment and 1 committed suicide after 2 months of high-dose treatment. Twenty-two had renal lupus, 14 had neurologic lupus, and 11 had other organ involvement. The outcome measure was the Responder Index for Lupus Erythematosus (complete response, partial response, no change, or worsening). At 6 months (the end of induction), 11 of 21 patients (52%) in the high-dose treatment group had a complete response compared with 9 of 26 patients (35%) in the traditional treatment group (P = 0.13). At the final visit (30 months), 10 of 21 patients (48%) in the high-dose treatment group had a complete response compared with 13 of 20 patients (65%) who continued with traditional treatment (P = 0.13). Six patients crossed over from traditional treatment to high-dose treatment because of lack of response, and 3 of those patients became complete responders. Conclusion There was not strong evidence that monthly IV cyclophosphamide and high-dose IV cyclophosphamide differed in complete or in any (complete or partial) response to induction or maintenance therapy. However, nonresponders to monthly IV cyclophosphamide can sometimes be rescued with high-dose IV cyclophosphamide. [source] Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: Findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial,ARTHRITIS & RHEUMATISM, Issue 1 2010Ellen M. Ginzler Objective To assess the effect of mycophenolate mofetil compared with intravenous pulses of cyclophosphamide on the nonrenal manifestations of lupus nephritis. Methods Patients with active lupus nephritis (renal biopsy class III, IV, or V) were recruited for the study (n = 370) and treated with mycophenolate mofetil (target dosage 3 gm/day) or intravenous cyclophosphamide (0.5,1.0 gm/m2/month), plus tapered prednisone, for 24 weeks. Nonrenal outcomes were determined using measures of whole body disease activity, including the British Isles Lupus Assessment Group (BILAG) disease activity index, the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and immunologic variables. Results Both treatments were effective on whole body disease activity in the systems examined, as indicated by changes in the classic BILAG index. With either treatment, remission was induced, notably in the mucocutaneous, musculoskeletal, cardiovascular/respiratory, and vasculitis systems, and flares were rare, as measured by the SELENA,SLEDAI. Levels of complement C3, C4, and CH50 and titers of anti,double-stranded DNA antibodies were normalized after treatment with either mycophenolate mofetil or intravenous cyclophosphamide. Conclusion In addition to the efficacy of both treatments on the renal system, this analysis showed that remission could also be induced in other systems. There was no clear difference in efficacy between mycophenolate mofetil and intravenous cyclophosphamide in ameliorating either the renal or nonrenal manifestations. Mycophenolate mofetil is, therefore, a suitable alternative to cyclophosphamide for the treatment of renal and nonrenal disease manifestations in patients with biopsy-proven lupus nephritis. [source] Modern therapeutic strategies for paediatric systemic lupus erythematosus and lupus nephritisACTA PAEDIATRICA, Issue 7 2010Stephen D Marks Abstract There is still a significant morbidity and mortality associated with childhood-onset systemic lupus erythematosus (SLE), despite an increasing armamentarium of immunosuppressive agents. The ideal therapeutic strategy for children and adolescents with SLE should provide the right amount of treatment to allow normal growth, development and fertility while reducing the disease activity and damage that can be accrued over the years. Each patient should have individualized treatments tailored to their organ involvement, disease severity and history of flares together with recent clinical, haematological and immunological parameters to avoid further flares of disease activity and side-effects of treatment, especially severe infections and future malignancies. The most commonly cited side-effects of medications include Cushingoid features of corticosteroids, infective complications of cyclophosphamide and gastrointestinal side-effects of mycophenolate mofetil. There is increasing evidence to support the use of oral mycophenolate mofetil as opposed to cyclophosphamide for both induction and maintenance therapies in many children with SLE with or without lupus nephritis (LN). Recently, case series utilizing B-lymphocyte depletion therapies with rituximab look promising for patients with severe or refractory disease activity. In this article, we explore current evidence to effectively treat children and adolescents with SLE with or without LN. Conclusion:, Modern therapeutic strategies include reduced doses and use of corticosteroids and intravenous cyclophosphamide respectively, with increased use of azathioprine, MMF and rituximab. [source] | ||||||||||