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To evaluate safety and efficacy of intravenous pulse cyclophosphamide (CyP) in acute macular serpiginous choroiditis (SC).
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In this chemotherapy-induced animal model of HCC, SLBZP was most efficacious as adjunctive therapy and appears to act by inhibiting tumor growth promoters and anti-apoptotic proteins while enhancing pro-apoptotic proteins.
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Ninety seven women have reached menopause at a median age of 44 years. Menopause has been surgically induced in 36% of women. In multivariate analysis, risk factors for non-surgical menopause included exposure to alkylating agents, increasing radiation dose to the ovaries, procarbazine dose, cyclophosphamide dose and unilateral oophorectomy. The highest risk ratio for non-surgical menopause was observed for women treated after the onset of puberty with alkylating agents, either alone (RR = 9, 95% CI: 2.7-28, P = 0.0003) or associated with even a low dose of radiation to the ovaries (RR = 29, 95% CI: 8-108, P < 0.0001). Exposure to unilateral oophorectomy is associated with a 7-year earlier age at menopause. By the age of 40, only 2.1% had non-surgical premature menopause and its main risk factors were age at diagnosis, cyclophosphamide dose, exposure to melphalan and radiation dose to the ovaries.
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The most widely accepted conditioning regimen to allogeneic hematopoietic stem cell transplantation consists of total body irradiation, especially in patients affected by acute lymphoblastic leukemia (ALL). In this retrospective study, we report our experience on hematopoietic stem cell transplantation in 44 pediatric patients with acute lymphoblastic leukemia using a non-radiation-based conditioning regimen (busulfan/cyclophosphamide). Median age at transplantation was 12.5 years (range, 4 to 14 y). 39 out of 44 patients received transplants in complete remission. At a median follow-up of 390 days, the probabilities of 3-year disease-free survival and overall survival were 50% and 68%, respectively. Disease status of hematopoietic stem cell transplantation was the only significant variable affecting the overall survival. Acute and chronic graft-versus-host disease occurred in 23 (64%) and 12(18%) patients, respectively. Relapse was significantly higher among patients transplanted in advanced disease status. The results of the study indicate that non-radiation-based preparative regimens can be used in pediatric patients with ALL. However, well-designed comparative trials are needed to better clarify the difference between radiation and non-radiation-based conditioning regimens in pediatric ALL.
Oocytes have a vast repertoire of active MDRs. The implications of this study are that these protective mechanisms are important during oogenesis and that these activities change with maturation, increasing susceptibility to toxicants. Future directions may exploit the up-regulation of these transporters during gonadotoxic therapy.
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A prospective national protocol for children with classical HL was implemented in Morocco to increase EFS by careful risk stratification, providing each cycle of therapy on time, decreasing treatment abandonment, improving communication among healthcare providers, and improving data collection. Patients were stratified into a favorable risk group (Ann Arbor stages I and II, no B symptoms, no bulky disease, and no contiguous (E) lesions) and received four cycles of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) or an unfavorable risk group (all others) who received two cycles of vincristine, procarbazine, prednisone, and doxorubicin (OPPA) and four cycles of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP). All patients received involved-field radiotherapy 25.5 Gy after completion of chemotherapy. EFS was calculated counting death, relapse/resistant disease, and abandonment as events.
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Highly sensitised children in need of cardiac transplantation have overall poor outcomes because of increased risk for dysfunction of the cardiac allograft, acute cellular and antibody-mediated rejection, and vasculopathy of the cardiac allograft. Cardiopulmonary bypass and the frequent use of blood products in the operating room and cardiac intensive care unit, as well as the frequent use of homografts, have predisposed potential recipients of transplants to allosensitisation. The expansion in the use of ventricular assist devices and extracorporeal membrane oxygenation has also contributed to increasing rates of allosensitisation in candidates for cardiac transplantation. Antibodies to Human Leukocyte Antigen can be detected before transplantation using several different techniques, the most common being the "complement-dependent lymphocytotoxicity assays". "Solid-phase assays", particularly the "Luminex® single antigen bead method", offer improved specificity and more detailed information regarding specificities of antibodies, leading to improved matching of donors with recipients. Allosensitisation prolongs the time on the waiting list for potential recipients of transplantation and increases the risk of complications and death after transplantation. Aggressive reduction of antibodies to Human Leukocyte Antigen in these high-risk patients is therefore of vital importance for long-term survival of the patient and cardiac allograft. Strategies to decrease Panel Reactive Antibody or percent reactive antibody before transplantation include plasmapheresis, intravenous administration of immunoglobulin, and specific treatment to reduce B-cells, particularly Rituximab. These strategies have resulted in varying degrees of success. Antibody-mediated rejection and cardiac allograft vasculopathy are two of the most important complications of transplantation in patients with high Panel Reactive Antibody. The treatment of antibody-mediated rejection in recipients of cardiac transplants is largely empirical and includes the use of high-dose corticosteroids, plasmapheresis, intravenous administration of immunoglobulins, anti-thymocyte globulin, and Rituximab. Cardiac allograft vasculopathy is believed to be secondary to chronic complement-mediated endothelial injury and chronic vascular rejection. The use of proliferation signal inhibitors, such as sirolimus and everolimus, has been shown to delay the progression of cardiac allograft vasculopathy. In some non-sensitised recipients of cardiac transplants, the de novo formation of antibodies to Human Leukocyte Antigen after transplantation may increase the likelihood of adverse clinical outcomes. The use of serial testing for donor-specific antibodies after cardiac transplantation may be advisable in patients with frequent episodes of rejection and patients with history of sensitisation. Allosensitisation before transplantation can negatively influence outcomes after transplantation. A high incidence of antibody-mediated rejection and graft vasculopathy can result in graft failure and decreased survival. Current strategies to decrease allosensitisation have helped to expand the pool of donors, improve times on the waiting list, and decrease mortality. Centres of transplantation offering desensitisation are currently using plasmapheresis to remove circulating antibodies; intravenous immunoglobulin to inactivate antibodies; cyclophosphamide to suppress B-cell proliferation; and Rituximab to deplete B-lymphocytes. Similar approaches are also used to treat antibody-mediated rejection after transplantation with promising results.
Gastrointestinal diffuse large B cell lymphoma (DLBCL) is a common subtype of extranodal lymphoma. There has been uncertainty about the clinical efficacy of combination therapy (surgery and chemotherapy) for gastrointestinal DLBCL. We retrospectively analyzed 114 patients with newly diagnosed gastrointestinal DLBCL from six medical centers. We evaluated four groups based on whether they were treated with or without surgery as the initial treatment for DLBCL, followed by either a regimen with cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) or CHOP with rituximab (R-CHOP). For all patients, treatment with R-CHOP resulted in significantly greater overall survival (OS; 93.2 vs. 74.5%, p = 0.008) and progression-free survival (89.8% vs. 72.7, p = 0.029). Tumor resection did not improve OS (84.0 vs. 85.0%, for surgery and chemotherapy alone, respectively, p = 0.980). However, for younger patients, overall survival was greater (p = 0.005) for patients treated with surgery plus chemotherapy (83.9%) than for patients treated with chemotherapy alone (40.0%). Elevated serum lactate dehydrogenase level (p = 0.004) and performance status (Eastern Cooperative Oncology Group; p = 0.003) were independent predictors of survival in patients with gastrointestinal DLBCL. Stage-modified IPI was recognized as the best prognostic tool. There were significant differences among patients with low-risk, intermediate-risk, and high-risk groups in 50-month OS (94.2 vs. 84.0 vs. 66.7%, p = 0.008). The results of this large-scale study suggest that R-CHOP regimen is the first-line treatment for gastrointestinal DLBCL. The benefit of surgery for these patients remains controversial. Further prospective analyses are warranted.
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Ginsenoside Rg3 is one of the active ingredients isolated from Panax ginseng C.A. Meyer. Previous investigation demonstrated that Rg3 was stereospecific in promotion of the immune response. The present study was designed to evaluate Rg3 and its epimers, 20(R)-Rg3 and 20(S)-Rg3, for their effects on oxidative stress induced by cyclophosphamide (Cy) in mice. Forty-eight mice were randomly distributed into 6 groups and intraperitoneally administered saline solution, Cy, 20(R)-Rg3, 20(S)-Rg3, 20(R)-Rg3+Cy or 20(S)-Rg3+Cy. After that, the spleen, thymus and serum were collected to measure the indices of the organs and oxidative parameters. The results showed that Rg3 significantly inhibited Cy-induced oxidative stress in mice by increasing the indices of the spleen and thymus and total antioxidant capacity, elevating the activities of catalase, superoxidase dismutase and lysozyme as well as decreasing the activity of xanthine oxidase and the levels of malondialdehyde and nitric oxide. Rg3 was stereospecific in antioxidant activities as R form exhibited significantly higher antioxidant effects than S form. Therefore, R form should be used when Rg3 is considered to be used as an antioxidant agent.
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Previously, different nonsteroidal anti-inflammatory drugs (NSAIDs) have been evaluated for their potential immunomodulatory activities. Mefenamic acid is a well-known NSAID and is used in the treatment of musculoskeletal disorders, inflammation, fever, and pain. To the best of our knowledge, promising data regarding the immunomodulatory activity of mefenamic acid is scarce. Current study investigates the immunomodulatory activity of mefenamic acid in different models of cell-mediated and humoral immunity.
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Patients with irresectable granulosa cell tumors (GCTs) often receive chemotherapy. The effectiveness of this approach, however, is uncertain. The aim of our study was to assess the response rate to chemotherapy for residual and recurrent inoperable GCT.
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A systematic review of purine analogs revealed heterogeneity between trials in treatment effects on response and progression free survival, but not survival, perhaps partly due to variations in analytical methods. In addition, combination treatments required evaluation. Therefore, individual patient data were sought for all randomized trials in untreated chronic lymphocytic leukemia which involved a purine analog, but which did not include antibody therapies. Sixteen trials were found, addressing seven comparisons. Eight trials, with 2,753 patients, showed that single agent purine analog improved progression free survival (odds ratio=0.71; 95% confidence interval=0.63-0.79). Heterogeneity remained substantial. Three trials, with 1,403 patients, showed that progression free survival was further improved by the addition of cyclophosphamide (odds ratio=0.54; 0.47-0.62). Fewer data were available on the addition of other drugs to purine analog, and none showed clear benefit. Two trials, with 544 patients, suggested cladribine improved progression free survival compared to fludarabine (odds ratio=0.77; 0.63-0.95). No differences were seen in overall survival for any comparisons. In conclusion, purine analogs, particularly combined with cyclophosphamide, significantly improve progression free survival but not survival. Some groups, such as the elderly, may not see the same benefits and maximizing doses may be important for all treatments, including chlorambucil. Longer follow up, consistent definitions and detailed reporting of trials should be encouraged.
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While cyclophosphamide (CYC) can save the life of a young woman with severe rheumatologic disease, it may lead to the long-term side-effects of infertility and premature menopause. We compared the reproductive health histories of young women with rheumatologic disease with and without prior CYC exposure to identify the impact of this medication on this important component of health.
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We identified 24 and analyzed data from 22 patients. 12 were male (54.5%) and 10 female (45.4%) and their median age was 55 years (range: 19-83). Most patients had localized disease at the time of diagnosis (n = 19, 86.3%), the most common site was the spine (n = 11, 50%) and the most common histology was diffuse large B-cell lymphoma. 21 patients received chemotherapy as initial therapy and 16 received combined chemoradiation. 81.8% of the patients (n = 18) achieved complete remission. 5-year survival rate was 86.3% and overall survival was found to be affected by the patients' initial response to treatment.
Current evidence indicates that the abnormal expression of chemokines or their receptors, such as CXC chemokine receptor-4 (CXCR4), is positively correlated with the development, progression and metastasis of tumor cells. However, the role of CXCR4 in neuroblastoma and its response to chemotherapy remain largely unclear. In addition, forkhead box 3 (Foxp3), a transcription factor associated with T cell tolerance, is expressed in tumor cells and plays a role in the immune evasion of cancers. The present study aimed to examine the expression of CXCR4 and Foxp3 in the LAN-5 and SK-N-SH neuroblastoma cell lines. The effects of chemotherapy drugs, cyclophosphamide (CTX) and pirarubicin (THP), on the expression of these two genes were also investigated. Our findings indicated that CXCR4 and Foxp3 were highly expressed in LAN-5 and SK-N-SH cells. Following treatment with CTX and THP, the protein expression of CXCR4 in LAN-5 and SK-N-SH cells was significantly decreased (P<0.05). The expression of Foxp3 in LAN-5 cells was also significantly downregulated by CTX and THP treatment (P<0.05). Therefore, the high expression of CXCR4 and Foxp3 in LAN-5 and SK-N-SH cells and their subsequent downregulation following administration of the chemotherapy agents suggests that the chemokine receptors, CXCR4 and Foxp3, may be involved in the metastasis and tumor evasion of neuroblastoma. Further studies should investigate the expression of CXCR4 and Foxp3 in patient samples.
Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by congenital abnormalities and chromosomal breakages with the occurrence of hematological and solid malignancies. FA is the most common type of inherited bone marrow failure and poses tremendous challenges. FA patients are uniquely hypersensitive to hematopoietic stem cell transplantation (HSCT) conditioning agents due to the underling chromosomal instability. HSCT has shown important progress in the last years, especially after the introduction of fludarabine and the reduction of cyclophosphamide in the preparative regimen. For patients with HLA-identical-related donors HSCT should be performed as first-line therapy, for patients with alternative donors HSCT remains a therapy with increased morbidity and mortality.
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The VEGFA -634CC genotype was found to be associated with an inferior prognosis for patients with HER2-positive breast cancer.
Transforming growth factor-β activated kinase-1 (TAK1, Map3k7), a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, is essential in innate and adaptive immune responses. We postulated that blockade of TAK1 would affect autoimmune diabetes in non-obese diabetic (NOD) mice. Administration of 5Z-7-oxozeaenol (OZ), a TAK1 inhibitor, decreased the incidence and delayed the onset of autoimmune diabetes in both spontaneous and accelerated (cyclophosphamide-induced) experimental NOD mice. OZ also reduced insulitis, preserved islet function, increased the expression of α1- antitrypsin (AAT), and severely inhibited NF-κB and JNK/AP-1 signaling pathways in immune organs and pancreatic tissues. Importantly, TAK1 inhibition by OZ elicited a Th1 to Th2 cytokine shift, and increased TGF-β1 production in cultured T lymphocytes supernatants. Systemic TAK1 inhibition induced immature DCs with lower expressions of MHC-II and CD86, attenuated DC-mediated T cell proliferation in allogeneic MLR, and production of cytokine IL-12p70 in DCs suspensions. The results indicate that TAK1 inhibition with OZ was associated with a lower frequency of autoimmune diabetes in NOD mice. The net effect of TAK1 inhibition in NOD mice therefore appears to be protective rather than disease-enhancing. Strategies targeting TAK1 specifically in NOD mice might prove useful for the treatment of autoimmune diabetes in general.
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Among these 81 patients, the incidence of ISAE was 7.4% in the non-anthracycline platinum group. The most commonly reported ISAE were swelling (3%), extravasation (3%), and phlebitis (3%). When stratified by regimen, fosaprepitant was associated with a statistically significant increased risk of ISAE in the anthracycline group (OR 8.1; 95% CI 2.0-31.9) compared to the platinum group.
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Several studies have shown that more than half of cancer patients have unrecognized renal insufficiency (RI), which is a reduced glomerular filtration rate (GFR) with normal serum creatinine. The aim of this study was to determine whether unrecognized RI is associated with an increased risk for chemotherapy-associated adverse effects in breast cancer patients treated with combined doxorubicin and cyclophosphamide treatment. GFR was estimated for 95 breast cancer patients from January 2005 to August 2009 using the Cockcroft-Gault formula. Unrecognized RI was defined as GFR less than 75 ml/min/1.73 m and the patients were grouped according to their estimated GFR. Logistic regression models were used to assess the effect of GFR on clinical outcomes. In total, 49 (52%) patients experienced at least one of the following chemotherapy-associated adverse effects during the course of treatment: an episode of neutropenic fever with hospital admission, a delay in chemotherapy treatment for a medical reason, a need for dose adjustment because of toxicity of the chemotherapeutic drugs, and the need for use of granulocyte colony-stimulating factor. The incidence of these adverse effects occurred more frequently in patients with GFR less than 75 compared with patients with GFR at least 75 (64 vs. 42%, odds ratio 5.29, 95% confidence interval 2.10-13.33) and remained statistically significant after adjustment for age, BMI, and initial doses of chemotherapeutic drugs (odds ratio 3.56, 95% confidence interval 1.08-11.67). Neutropenic fever, dose delay, and dose adjustment as separate outcomes occurred more frequently in the GFR less than 75 group but lost statistical significance after adjustment. Our results demonstrate that unrecognized RI is associated with an increased risk for chemotherapy-associated adverse events in this patient population. Further prospective studies are required to determine whether a dose reduction in patients with unrecognized RI reduces adverse effects without adversely affecting the benefit of treatment.
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There are some nail abnormalities described in systemic lupus erythematosus (SLE).
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To analyze clinical features and outcomes of non-upper aerodigestive tract NK/T-cell lymphoma (NUAT-NKTCL).
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The constellation of "white dot syndromes" and systemic symptoms necessitates a general work-up to exclude granulomatous disorders such as sarcoidosis or tuberculosis. Delayed diagnosis of cardiac sarcoidosis may have life-threatening consequences and the ophthalmologist may be the first physician to diagnose the condition.
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Germ cells tumours can present in primary extra-gonadal locations. It is difficult to distinguish a retroperitoneum primary germ cell tumour from metastatic disease of a clinically undetected gonadal tumour or one that has regressed, like the situation described in the case presented.
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Female SD rats were injected with cyclophosphamide (75 mg/kg) intraperitoneally at day 1, 4, 7 and 10 to induce chronic cystitis. Saline was injected in the same protocol for controls. Bladder specimens were cut at 8 μm thickness, fixed in 70% ethanol and lightly stained by hematoxylin and eosin, and then superficial urothelium, intermediate/basal urothelium and detrusor muscles were laser-captured separately. Real-time PCR was performed to examine expressions of α-SMA, CK20, muscarinic 2 receptors (M2R) and muscarinic 3 receptors (M3R).