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Additional Cycles (additional + cycle)
Selected AbstractsManagement of nonresponse to rituximab in rheumatoid arthritis: Predictors and outcome of re-treatmentARTHRITIS & RHEUMATISM, Issue 5 2010E. M. Vital Objective A proportion of patients with rheumatoid arthritis (RA) have disease that fails to respond to an initial cycle of rituximab. Using highly sensitive flow cytometry (HSFC), it has been shown that most patients who do not exhibit a response, as measured using the European League Against Rheumatism (EULAR) criteria, have persistent circulating B cell levels at week 2 after initial treatment with rituximab. This study was undertaken to examine whether an additional cycle of rituximab would improve B cell depletion and clinical response in patients whose disease did not respond to the initial cycle. Methods Patients with RA (n = 158) were treated with a first cycle of rituximab (2 infusions of 1 gm each). Clinical responses were assessed using EULAR criteria, and patients were categorized as either first-cycle responders or first-cycle nonresponders. Baseline characteristics of first-cycle nonresponders (n = 38) and first-cycle responders (n = 65) with complete data were compared. First-cycle nonresponders (n = 25) were treated with a second cycle of rituximab at least 6 months after the first cycle. HSFC was performed at baseline, immediately prior to the second infusion (week 2), 1 month after the second infusion (week 6), and then every 3 months for each cycle of rituximab. Complete B cell depletion was defined as being <0.0001 × 109 cells/liter. Results At baseline, the number of preplasma cells was significantly higher in first-cycle nonresponders than in first-cycle responders (P = 0.003). Following the first infusion of the first cycle of rituximab, only 9% of first-cycle nonresponders (3 of 34) exhibited complete depletion of B-lineage cells, compared with 37% of first-cycle responders (22 of 59) (P = 0.007). Following the first infusion of the second cycle of rituximab, 38% of first-cycle nonresponders exhibited complete depletion. Twenty-six weeks after the second cycle, there was a significant improvement in the Disease Activity Score in 28 joints, with 72% of patients exhibiting a EULAR response. Conclusion RA patients whose disease did not respond to an initial cycle of rituximab have higher circulating preplasma cell numbers at baseline and incomplete depletion. Our findings indicate that an additional cycle of rituximab administered prior to total B cell repopulation enhances B cell depletion and clinical responses. [source] Combination therapy with rituximab and intravenous or oral fludarabine in the first-line, systemic treatment of patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type,,CANCER, Issue 22 2009Antonio Salar MD Abstract BACKGROUND: Currently, there are no consensus guidelines regarding the best therapeutic option for patients with extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue (MALT) type. METHODS: Patients with systemically untreated or de novo extranodal MALT lymphoma received rituximab 375 mg/m2 intravenously on Day 1 and fludarabine 25 mg/m2 intravenously on Days 1 through 5 (Days 1-3 in patients aged >70 years) every 4 weeks, for 4 to 6 cycles. After the first cycle, oral fludarabine could be given orally at 40 mg/m2 on the same schedule. After 3 cycles, a workup was done. Patients who achieved a complete remission (CR) received an additional cycle, and patients who achieved a partial remission (PR) received a total of 6 cycles. RESULTS: Twenty-two patients were studied, including 12 patients with gastric lymphoma and 10 patients with extragastric MALT lymphoma. Six patients (27%) had stage IV disease. In total, 101 cycles were administered (median, 4 cycles per patients). After the third cycle, 13 patients (62%) achieved a CR, and 8 patients (38%) achieved a PR. Primary extragastric disease was an adverse factor to achieve CR after 3 cycles of chemotherapy (hazard ratio, 23.3; 95% confidence interval, 2.0-273.3). At the end of treatment, the overall response rate was 100%, and 90% of patients achieved a CR. The progression-free survival rate at 2 years in patients with gastric and extragastric MALT lymphoma was 100% and 89%, respectively. Toxicities were mild and mainly were hematologic. CONCLUSIONS: Combination therapy with rituximab and fludarabine is a very active treatment with favorable safety profile as first-line systemic treatment for patients with extranodal MALT lymphoma. Cancer 2009. © 2009 American Cancer Society. [source] Ab initio structure solution by iterative phase-retrieval methods: performance tests on charge flipping and low-density eliminationJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 1 2010Frank Fleischer Comprehensive tests on the density-modification methods charge flipping [Oszlányi & Süt, (2004). Acta Cryst. A60, 134,141] and low-density elimination [Shiono & Woolfson (1992). Acta Cryst. A48, 451,456] for solving crystal structures are performed on simulated diffraction data of periodic structures and quasicrystals. A novel model-independent figure of merit, which characterizes the reliability of the retrieved phase of each reflection, is introduced and tested. The results of the performance tests show that the quality of the phase retrieval highly depends on the presence or absence of an inversion center and on the algorithm used for solving the structure. Charge flipping has a higher success rate for solving structures, while low-density elimination leads to a higher accuracy in phase retrieval. The best results can be obtained by combining the two methods, i.e. by solving a structure with charge flipping followed by a few cycles of low-density elimination. It is shown that these additional cycles dramatically improve the phases not only of the weak reflections but also of the strong ones. The results can be improved further by averaging the results of several runs and by applying a correction term that compensates for a reduction of the structure-factor amplitudes by averaging of inconsistently observed reflections. It is further shown that in most cases the retrieved phases converge to the best solution obtainable with a given method. [source] Toremifene for premenstrual mastalgia: a randomised, placebo-controlled crossover studyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 6 2006S Oksa Objective, To investigate the efficacy of toremifene in the treatment of premenstrual mastalgia. Design, Double-blind, placebo-controlled crossover study. Setting, Three Finnish general practices from the districts of Satakunta Central Hospital and Tampere University Hospital. Population, A total of 62 women aged 25,45 years with premenstrual mastalgia during at least three previous menstrual cycles. Methods, Women were randomised to receive toremifene 20 mg daily or placebo from day 15 of the menstrual cycle until menstruation for three consecutive cycles. After a wash-out cycle, the women were crossed over to receive placebo or toremifene for three additional cycles. Main outcome measures, Cyclic breast pain relief assessed by visual analogue scale (VAS) score. Quality-of-life scores assessed by a modified 36-item Finnish Depression Scale, with a score ranging from 0 to 108. Acceptability of treatment. Results, About 32 women were randomised to receive toremifene first and 30 to receive placebo first. Twenty-nine and 27 participants in the groups treated with toremifene first or placebo first completed the treatment, respectively. There were significant reductions in VAS scores in both groups after three treatment cycles. This was significantly greater in the toremifene-treated group (VAS: 1.8 in the toremifene group and 3.7 in the placebo group, P= 0.004). Treatment effect between treatment cycles was significant (P= 0.001). Quality of life was similar during the toremifene and placebo cycles. Conclusion, This study demonstrates that the antiestrogenic compound, toremifene, is able to relieve premenstrual breast pain without major adverse effects. There was a 64% reduction in median pain scores in the toremifene-treated cycles compared with a 26% reduction in placebo-treated cycles. [source] Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanomaCANCER, Issue 8 2008A phase II Cytokine Working Group study Abstract BACKGROUND. The combination of temozolomide (TMZ) and thalidomide was reported to produce a high response rate, including shrinkage of brain metastases, in patients with metastatic melanoma. The authors tested the efficacy of a regimen including TMZ, thalidomide, and whole brain radiation therapy (WBRT) in patients with brain (CNS) metastases from melanoma. METHODS. Patients with melanoma, CNS metastases documented by magnetic resonance imaging, and no prior systemic chemotherapy received WBRT, 30 Gray in 10 fractions, Days 1 to 5 and 8 to 12; TMZ, 75 mg/m2/day, Weeks 1 to 6; and thalidomide, 100 mg/day, Weeks 1 to 4, then escalated by 100 mg/day at Weeks 5, 7, and 9 as tolerated to a maximum of 400 mg/day. CNS and systemic tumor response was assessed at Week 10. Patients without CNS or clinically significant systemic disease progression received additional cycles of TMZ at 10-week intervals. RESULTS. Thirty-nine patients received treatment, and 3 exhibited CNS response (1 complete response, 2 partial responses) (response rate, 7.6%; 95% confidence interval, 0.7%-16.1%), all unconfirmed by repeat imaging. Seven patients had stable CNS disease at 10 weeks. No patient exhibited a systemic response. Only 4 patients received 2 cycles of therapy, and just 1 received 3. Median time to progression was 7 weeks, and median overall survival was 4 months. Grade 3-4 side effects included deep venous thrombosis (3), pulmonary embolism (1), and CNS events (12). Eighteen (45%) patients required admission for side effects (7) and/or symptomatic disease progression (11). CONCLUSIONS. The efficacy of TMZ, thalidomide, and WBRT in the treatment of CNS metastatic melanoma is low. Other treatment approaches should be considered for this patient population. Cancer 2008. © 2008 American Cancer Society. [source] Phase II study of pemetrexed in combination with carboplatin in the first-line treatment of advanced nonsmall cell lung cancerCANCER, Issue 11 2005Ralph G. Zinner M.D. Abstract BACKGROUND The primary objectives of this study were to determine the efficacy and tolerability of a pemetrexed-carboplatin combination as first-line therapy in patients with advanced nonsmall cell lung cancer. METHODS Eligibility criteria included Zubrod performance status of 0 or 1, Stage IIIB (malignant effusion) or IV disease, and no prior chemotherapy. Treatment was pemetrexed 500 mg/m2 given intravenously and carboplatin area under the serum concentration,time curve = 6 given intravenously on Day 1 every 3 weeks for six cycles; patients could receive additional cycles at the discretion of the treating physician and patient. All patients received folic acid, vitamin B12, and dexamethasone prophylaxis. RESULTS Fifty patients (31 men and 19 women) were treated. The median age was 62 years. Ninety-six percent of patients had Stage IV disease, and 88% had a performance status of 1. The median number of cycles was 6; 15 patients received 8 or more cycles. There was Grade 3/4 neutropenia in 11 (22%) and 2 (4%) patients, respectively; Grade 3/4 thrombocytopenia in 1 (2%) and 0 patients, respectively. Three patients (6%) experienced Grade 3 nonhematologic side effects (diarrhea, neutropenic pneumonia, and fatigue). No patients had sensory neuropathy or alopecia >Grade 1. The partial response rate was 24%, median time to progression 5.4 months, 1-year survival 56.0%, and median survival 13.5 months. CONCLUSIONS This is an active, very well-tolerated regimen. Trials focused on how to integrate this doublet with novel agents are warranted. Cancer 2005. © 2005 American Cancer Society. [source] | ||||||||||