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High Response Rate (high + response_rate)
Selected AbstractsHigh response rate and manageable toxicity with an intensive, short-term chemotherapy programme for Burkitt's lymphoma in adultsBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2004Massimo Di Nicola Summary A very short, intensive paediatric chemotherapy programme was tested in a consecutive monoinstitutional group of 22 adult Burkitt's lymphoma (BL) patients. After a 5-week induction phase of weekly infusions consisting of vincristine, cyclophosphamide, doxorubicin, high-dose (HD) methotrexate (MTX) plus leukovorin rescue, and intrathecal MTX or cytarabine (ARA-C), a consolidation phase including HD ARA-C plus cisplatin was given. Responding patients achieving less than complete response (CR) after completion of the initial induction phase, were promptly shifted to a high-dose, stem cell supported sequential chemotherapy schema (R-HDS). Patient characteristics: median age, 35·5 (range 18,76) years; Ann Arbor stage I,II/III,IV, 11/11; bulky disease, 15 patients; LDH , 460 U/l, 11 patients. The median duration of the chemotherapy programme was 62 d (range, 43,94 d). Seventeen patients achieved a CR (77%), one patient died of progressive disease and four partial responders following induction were converted to CR following R-HDS. Of 17 patients in CR, one died of infectious toxicity while in CR, and one relapsed at 30 months and died of progressive disease. After a median follow-up of 28·7 months (range, 6,158 months), 16 patients (73%) were in continued CR. Overall survival and progression-free survival were 77% [95% confidence interval (CI), 52,99%] and 68% (95% CI, 43,99%) respectively. Confirmation of these excellent efficacy and feasibility results by larger, multicentre and prospective studies is warranted. [source] High response rate after intratumoral treatment with interleukin-2CANCER, Issue 17 2010Results from a phase 2 study in 51 patients with metastasized melanoma Abstract BACKGROUND: Systemic high-dose interleukin-2 (IL-2) achieved long-term survival in a subset of patients with advanced melanoma. The authors reported previously that intratumorally applied IL-2 induced complete local responses of all metastases in >60% of patients. The objectives of the current study were to confirm those results in a larger cohort and to identify patient or regimen characteristics associated with response. METHODS: Patients with melanoma who had a median of 12 injectable metastases received intratumoral IL-2 treatments 3 times weekly until they achieved clinical remission. The initial dose of 3 million international units was escalated, depending on the individual patient's tolerance. RESULTS: Forty-eight of 51 patients were evaluable. Only grade 1/2 toxicity was recorded. A complete response that lasted ,6 months was documented in 70% of all injected metastases. A complete local response of all treated metastases was achieved in 33 patients (69%), including 11 patients who had between 20 and 100 metastases. Response rates were higher for patients who had stage III disease compared with patients who had stage IV disease. No objective responses of distant untreated metastases were observed. The 2-year survival rate was 77% for patients with stage IIIB/IIIC disease and 53% for patients with stage IV disease. Efficacy and survival did not differ between patients who had ,20 lesions and patients who had <20 lesions. CONCLUSIONS: Intratumoral IL-2 treatment elicited complete local responses in a high percentage of patients. Further studies will be required to investigate the mode of action of this treatment and its impact on survival. Cancer 2010. © 2010 American Cancer Society. [source] Pathological gambling: an increasing public health problemACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2001Article first published online: 7 JUL 200 Gambling has always existed, but only recently has it taken on the endlessly variable and accessible forms we know today. Gambling takes place when something valuable , usually money , is staked on the outcome of an event that is entirely unpredictable. It was only two decades ago that pathological gambling was formally recognized as a mental disorder, when it was included in the DSM-III in 1980. For most people, gambling is a relaxing activity with no negative consequences. For others, however, gambling becomes excessive. Pathological gambling is a disorder that manifests itself through the irrepressible urge to wager money. This disorder ultimately dominates the gambler's life, and has a multitude of negative consequences for both the gambler and the people they interact with, i.e. friends, family members, employers. In many ways, gambling might seem a harmless activity. In fact, it is not the act of gambling itself that is harmful, but the vicious cycle that can begin when a gambler wagers money they cannot afford to lose, and then continues to gamble in order to recuperate their losses. The gambler's ,tragic flaw' of logic lies in their failure to understand that gambling is governed solely by random, chance events. Gamblers fail to recognize this and continue to gamble, attempting to control outcomes by concocting strategies to ,beat the game'. Most, if not all, gamblers try in some way to predict the outcome of a game when they are gambling. A detailed analysis of gamblers' selfverbalizations reveals that most of them behave as though the outcome of the game relied on their personal ,skills'. From the gambler's perspective, skill can influence chance , but in reality, the random nature of chance events is the only determinant of the outcome of the game. The gambler, however, either ignores or simply denies this fundamental rule (1). Experts agree that the social costs of pathological gambling are enormous. Changes in gaming legislation have led to a substantial expansion of gambling opportunities in most industrialized countries around the world, mainly in Europe, America and Australia. Figures for the United States' leisure economy in 1996 show gross gambling revenues of $47.6 billion, which was greater than the combined revenue of $40.8 billion from film box offices, recorded music, cruise ships, spectator sports and live entertainment (2). Several factors appear to be motivating this growth: the desire of governments to identify new sources of revenue without invoking new or higher taxes; tourism entrepreneurs developing new destinations for entertainment and leisure; and the rise of new technologies and forms of gambling (3). As a consequence, prevalence studies have shown increased gambling rates among adults. It is currently estimated that 1,2% of the adult population gambles excessively (4, 5). Given that the prevalence of gambling is related to the accessibility of gambling activities, and that new forms of gambling are constantly being legalized throughout most western countries, this figure is expected to rise. Consequently, physicians and mental health professionals will need to know more about the diagnosis and treatment of pathological gamblers. This disorder may be under-diagnosed because, clinically, pathological gamblers usually seek help for the problems associated with gambling such as depression, anxiety or substance abuse, rather than for the excessive gambling itself. This issue of Acta Psychiatrica Scandinavica includes the first national survey of problem gambling completed in Sweden, conducted by Volberg et al. (6). This paper is based on a large sample (N=9917) with an impressively high response rate (89%). Two instruments were used to assess gambling activities: the South Oaks Gambling Screen-Revised (SOGS-R) and an instrument derived from the DSM-IV criteria for pathological gambling. Current (1 year) and lifetime prevalence rates were collected. Results show that 0.6% of the respondents were classified as probable pathological gamblers, and 1.4% as problem gamblers. These data reveal that the prevalence of pathological gamblers in Sweden is significantly less than what has been observed in many western countries. The authors have pooled the rates of problem (1.4%) and probable pathological gamblers (0.6%), to provide a total of 2.0% for the current prevalence. This 2% should be interpreted with caution, however, as we do not have information on the long-term evolution of these subgroups of gamblers; for example, we do not know how many of each subgroup will become pathological gamblers, and how many will decrease their gambling or stop gambling altogether. Until this information is known, it would be preferable to keep in mind that only 0.6% of the Swedish population has been identified as pathological gamblers. In addition, recent studies show that the SOGS-R may be producing inflated estimates of pathological gambling (7). Thus, future research in this area might benefit from the use of an instrument based on DSM criteria for pathological gambling, rather than the SOGS-R only. Finally, the authors suggest in their discussion that the lower rate of pathological gamblers obtained in Sweden compared to many other jurisdictions may be explained by the greater availability of games based on chance rather than games based on skill or a mix of skill and luck. Before accepting this interpretation, researchers will need to demonstrate that the outcomes of all games are determined by other factor than chance and randomness. Many studies have shown that the notion of randomness is the only determinant of gambling (1). Inferring that skill is an important issue in gambling may be misleading. While these are important issues to consider, the Volberg et al. survey nevertheless provides crucial information about gambling in a Scandinavian country. Gambling will be an important issue over the next few years in Sweden, and the publication of the Volberg et al. study is a landmark for the Swedish community (scientists, industry, policy makers, etc.). This paper should stimulate interesting discussions and inspire new, much-needed scientific investigations of pathological gambling. Acta Psychiatrica Scandinavica Guido Bondolfi and Robert Ladouceur Invited Guest Editors References 1.,LadouceurR & WalkerM. The cognitive approach to understanding and treating pathological gambling. In: BellackAS, HersenM, eds. Comprehensive clinical psychology. New York: Pergamon, 1998:588 , 601. 2.,ChristiansenEM. Gambling and the American economy. In: FreyJH, ed. Gambling: socioeconomic impacts and public policy. Thousand Oaks, CA: Sage, 1998:556:36 , 52. 3.,KornDA & ShafferHJ. Gambling and the health of the public: adopting a public health perspective. J Gambling Stud2000;15:289 , 365. 4.,VolbergRA. Problem gambling in the United States. J Gambling Stud1996;12:111 , 128. 5.,BondolfiG, OsiekC, FerreroF. Prevalence estimates of pathological gambling in Switzerland. Acta Psychiatr Scand2000;101:473 , 475. 6.,VolbergRA, AbbottMW, RönnbergS, MunckIM. Prev-alence and risks of pathological gambling in Sweden. Acta Psychiatr Scand2001;104:250 , 256. 7.,LadouceurR, BouchardC, RhéaumeNet al. Is the SOGS an accurate measure of pathological gambling among children, adolescents and adults?J Gambling Stud2000;16:1 , 24. [source] Comprehensive validation of competencies for dental vocational training and general professional trainingEUROPEAN JOURNAL OF DENTAL EDUCATION, Issue 4 2003L. Prescott This paper outlines a study designed to validate competencies for dental vocational training (DVT) and general professional training (GPT) in order to ensure their accuracy and acceptability. A highly inclusive approach is described whereby all trainers in Scotland were invited to participate in the exercise. The 168 individuals recruited were drawn from all branches of the dental services and all regions in Scotland. Using online or paper questionnaires, quantitative and qualitative data were collected for each competency statement over 9 months, after which focus groups discussed and decided which changes should be made. A high response rate was observed and from the 160 competencies originally identified, almost half (47.5%) were redrafted as a direct result of the validation process. Sections of the competency document that required most attention are discussed, as are the nature of changes made to the competencies. As a result of this study, a fully validated competency document for DVT and GPT has been produced and will allow a high degree of standardization of training through the provision of essential consistent information to trainers and VDPs. [source] Simulation study of methemoglobin reduction in erythrocytesFEBS JOURNAL, Issue 6 2007Differential contributions of two pathways to tolerance to oxidative stress Methemoglobin (metHb), an oxidized form of hemoglobin, is unable to bind and carry oxygen. Erythrocytes are continuously subjected to oxidative stress and nitrite exposure, which results in the spontaneous formation of metHb. To avoid the accumulation of metHb, reductive pathways mediated by cytochrome b5 or flavin, coupled with NADH-dependent or NADPH-dependent metHb reductases, respectively, keep the level of metHb in erythrocytes at less than 1% of the total hemoglobin under normal conditions. In this work, a mathematical model has been developed to quantitatively assess the relative contributions of the two major metHb-reducing pathways, taking into consideration the supply of NADH and NADPH from central energy metabolism. The results of the simulation experiments suggest that these pathways have different roles in the reduction of metHb; one has a high response rate to hemoglobin oxidation with a limited reducing flux, and the other has a low response rate with a high capacity flux. On the basis of the results of our model, under normal oxidative conditions, the NADPH-dependent system, the physiological role of which to date has been unclear, is predicted to be responsible for most of the reduction of metHb. In contrast, the cytochrome b5,NADH pathway becomes dominant under conditions of excess metHb accumulation, only after the capacity of the flavin,NADPH pathway has reached its limit. We discuss the potential implications of a system designed with two metHb-reducing pathways in human erythrocytes. [source] Standardized health check data from community-dwelling elderly people: the potential for comparing populations and estimating needHEALTH & SOCIAL CARE IN THE COMMUNITY, Issue 1 2000Peter Bath PhD Abstract The main aim of this study was to compare EASY-Care data obtained during nurse-administered annual health checks in two populations of older people. A secondary aim was to determine whether a standardized assessment system administered as part of routine practice by a trained nurse during the over-75 health check could generate useful information for comparing population health and functional status of community-dwelling-older people. One hundred and seventy-nine elderly people (aged 75 years and over) from the Woodstock ward, Belfast, having relatively high deprivation; and 238 elderly people from south Hampshire, ranging from affluent wards in New Forest to inner city wards, were assessed using the EASY-Care assessment system as part of their annual health check. There was a high response rate to the standardized assessment in both populations (75% and 79%). Compared to people in south Hampshire, the people in Belfast had higher relative risk of having fair/poor self-rated health, and lower relative risk of having good/sufficient accommodation and of having difficulty chewing. People in Belfast had a higher relative risk of being dependent for six of the seven IADL items and for continence of urine, bathing, grooming, use of the stairs and dressing among the ADL items. The results demonstrate the ability of data generated by assessment system to discriminate between populations of older people when used as part of routine practice. Differences in health and functional status may be associated with deprivation. Data collected during the annual health check about the health and functional status of older people could provide a useful adjunct to census and survey data to measure population needs and to support locality planning. [source] Hepatic arterial infusion of floxuridine and dexamethasone plus high-dose Mitomycin C for patients with unresectable hepatic metastases from colorectal carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2005Nancy Kemeny MD Abstract Background In vitro data suggest increased cytotoxicity with Mitomycin C (Mit-C) and Floxuridine (FUDR). Based on these data, we performed a phase II trial of hepatic arterial infusion (HAI) of FUDR and Dexamethasone (Dex) plus high-dose Mit-C for patients with unresectable hepatic metastases from colorectal carcinoma. Methods High-dose Mit-C (15 mg/m2) was added via the pump sideport to HAI FUDR and Dex for 14 days of a 28-day cycle. Mit-C was given on days 1 and 29, and FUDR was given indefinitely until disease progression or discontinuation of therapy due to toxicity. Results Sixty-three patients with unresectable liver metastases were entered. The chemotherapy-naïve group (n,=,26) and those previously treated (n,=,37) had similar response and median survival: 73% and 70%, and 23 and 20 months, respectively. The major toxicities were liver bilomas (7.9%), elevation in bilirubin level >3 (22%), and biliary sclerosis (9.5%). Hematologic and gastrointestinal toxicity was less than 2%. Conclusion The addition of high-dose Mit-C to HAI FUDR and Dex produced a high response rate even in previously treated patients. The median survival was 21 months even though half the patients were previously treated with chemotherapy. Biliary toxicity was higher than expected; therefore, alternatives to high dose Mit-C should be investigated when exploring additions to HAI therapy with FUDR and Dex. J. Surg. Oncol. 2005;91:97,101. © 2005 Wiley-Liss, Inc. [source] Investigating the use of sampling for maximising the efficiency of student-generated faculty teaching evaluationsMEDICAL EDUCATION, Issue 2 2005Clarence D Kreiter Purpose, Surveys of medical students are widely used to evaluate course content and faculty teaching within the medical school. Gathering information that accurately reflects student perceptions requires that students buy into the evaluation process and be willing to provide thoughtful responses to the teaching evaluation. To maintain student commitment, it is important that medical students are not overburdened with poorly planned evaluations. Sampling might decrease the number of evaluations required of students and might also reduce the proportion of non-responses and other forms of inattentive response biases. Methods, A sampling technique employed within a large medical lecture is described and evaluated. A generalisability study of the teacher evaluations is conducted. Results, A high response rate and high levels of reliability were obtained by sampling a small proportion of the total class. The largest source of error was related to rater and utilising sufficient numbers of student-raters is critical to achieving reliable results. Conclusion, Sampling can reduce evaluation demands placed on students, and preserve reliability and increase the validity of mean evaluation scores. With computer presentation, efficient sampling techniques become practical and should be part of software packages used to present teacher evaluations. [source] Phase II study of S-1 and irinotecan combination chemotherapy as a first-line therapy for patients with advanced gastric cancer.ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2009Korean Cancer Study Group Protocol ST05-0 Abstract Background: Irinotecan plus intravenous 5-fluorouracil (5-FU) with leucovorin is effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine derivative and has a high response rate of about 40% for patients with advanced gastric cancer (AGC). We evaluated the antitumor activity and toxicities of an S-1 and irinotecan combination as a first-line therapy for patients with AGC. Methods: Patients with histologically confirmed unresectable or metastatic AGC were treated with S-1 40 mg/m2 PO twice daily on days 1,14 and irinotecan 150 mg/m2 i.v. on day 1 every 3 weeks until disease progression or unacceptable toxicities resulted. Results: A total of 45 patients were enrolled between September 2005 and March 2007. After a median of seven cycles of chemotherapy (range: 1,20, total: 350), 42 and 44 patients were evaluable for response and toxicity, respectively. On the intention-to-treat analysis, the overall response rate was 48.9% (95% C.I. 34.3,63.5%). The median time to progression was 5.7 months (95% C.I. 4.3,7.1) and the median overall survival was 10.4 months (95% C.I. 6.1,14.7). The commonly observed grade 3/4 adverse events were neutropenia (29.5% of patients) and vomiting (13.6%). Conclusion: An S-1 and irinotecan combination chemotherapy is active and tolerable as a first-line therapy for AGC. [source] A preoperative clinical prognostic model for non-metastatic renal cell carcinomaBJU INTERNATIONAL, Issue 9 2003L. Cindolo Authors from Naples, Paris and Rennes describe their efforts to develop a model for the preoperative prediction of outcome for non-metastatic renal cancer. It is valuable to both urologist and patient to develop such a model, particularly so on preoperative criteria. The results of their study are interesting, leading to possibly helpful findings. In another article, authors from Iceland estimated the risk of developing prostate and other cancer among relatives of men from that country diagnosed with prostate cancer. They found that a family history is a risk factor for prostate cancer, with the risk potentially higher for relatives of patients who died from the disease. From the relative dearth of papers on quality of life after radical prostatectomy there are now several, and the authors from Bristol report on the effects of erectile dysfunction on quality of life after this type of treatment. They had a very high response rate (91%) to their questionnaire, and found that erectile dysfunction has a profound effect on quality of life. This finding is not a surprise, but do we need to examine our management of prostate cancer in the light of it? OBJECTIVE To develop a model to predict the outcome before surgery for non-metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS The records of 660 patients with non-metastatic RCC, operated at three European medical institutes, were reviewed. Univariate and multivariate analyses were used to assess the clinical and pathological variables affecting disease-free survival. RESULTS The median (range) follow-up was 42 (2,180) months; the disease recurred in 110 patients (16%). The 2- and 5-year overall survival was 87% and 54%, respectively. Five variables were significant in the univariate analysis, i.e. clinical presentation, clinical and pathological size, tumour grade and stage (P < 0.05). The preoperative variables, e.g. clinical presentation and clinical tumour size, were retained from the multivariate model. A recurrence risk formula (RRF) was constructed from this model, as (1.28 × presentation (asymptomatic = 0; symptomatic = 1) + (0.13 × clinical size)). Using this equation, the 2- and 5-year disease-free survival was 96% and 93% for an RRF of ,,1.2 and 83% and 68% for an RRF of >,1.2. CONCLUSION A formula was developed which, independent of stage, can be used to predict the rate of treatment failure in patients who undergo nephrectomy for non-metastatic RCC. The RRF might be useful for more accurate sub-grouping of good-prognosis patients, and for counselling patients before surgery, their personalized follow-up or adjuvant treatment once available. [source] Ifosphamide, etoposide and epirubicin is an effective combined salvage and peripheral blood stem cell mobilisation regimen for transplant-eligible patients with non-Hodgkin lymphoma and Hodgkin diseaseBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2007Mark J. Bishton Summary A total of 143 patients with relapsed (n = 90), primary refractory (n = 32) and first line chemotherapy responsive (n = 21) non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD) were treated with IVE (ifosphamide, etoposide and epirubicin) chemotherapy with the intent to proceed to high-dose therapy with either autologous or allogeneic transplantation, following peripheral blood stem cell mobilisation. A major response (complete/partial response) to IVE was seen in 115 patients (80·4%) with 5-year overall survival (OS) and event free survival (EFS) of 53% and 43%, respectively. Subgroup analysis showed overall response rates of 93·1% for HD with a 5-year OS and EFS of 62% and 52% respectively, while NHL showed response rates of 78·0% with 5-year OS and EFS of 50% and 39% respectively. The median number of CD34 +ve cells mobilised following IVE was 7·86 × 106 (range 1·72,42·91 × 106), with 60% mobilising >2 × 106/kg in a single collection. Grade IV neutropenia was seen in 79·6% patients and 77/270 cycles required intravenous antibiotic treatment. We conclude that IVE has a high response rate across a range of refractory and relapsed lymphoma with acceptable toxicity and excellent PBSC mobilising characteristics. [source] A phase 2 study of yttrium-90 ibritumomab tiuxetan (Zevalin) in patients with chronic lymphocytic leukemiaCANCER, Issue 19 2009Nitin Jain MD Abstract BACKGROUND: Radioimmunotherapy (RIT) with radio-labeled monoclonal antibodies to CD20 produce a high response rate in patients with relapsed lymphoma. Use of this modality in patients with chronic lymphocytic leukemia (CLL) has been hampered by the extensive marrow involvement seen in patients with CLL, which would produce a high risk for marrow aplasia after treatment with RIT. Patients with lymphoma and marrow involvement have been treated with RIT if involved marrow was less than 25% of the total marrow. Thus, we adapted this approach as consolidation therapy in patients with CLL responding to chemoimmunotherapy. METHODS: Fourteen patients with relapsed CLL either in partial remission or in complete remission but with disease documented by flow cytometry were treated with 90Y ibritumomab tiuxetan. RESULTS: One patient responded and achieved a complete remission but with residual disease detected by flow cytometry. Of note was that grade 3 or 4 hematologic toxicity was seen in 12 of the 13 (92%) evaluable patients, with grade 3 or 4 thrombocytopenia noted in 11 (85%) of the patients. In addition, myelosuppression was prolonged with a median duration of grade 3 or 4 thrombocytopenia of 37 days. Five patients had persistent thrombocytopenia 3 months post-therapy. CONCLUSIONS: Even in patients with CLL and limited marrow involvement, the use of RIT results in unacceptable hematologic toxicity. Cancer 2009. © 2009 American Cancer Society. [source] Activity of cladribine combined with cyclophosphamide in frontline therapy for chronic lymphocytic leukemia with 17p13.1/TP53 deletion,CANCER, Issue 1 2009Report From the Polish Adult Leukemia Group Abstract BACKGROUD: The 17p13.1 deletion that causes loss of the p53-encoding TP53 gene is the most powerful predictor of a poor response to conventional therapy and shortened survival in patients with chronic lymphocytic leukemia (CLL). The results of this study have demonstrated that the cladribine and cyclophosphamide regimen may improve treatment results in this poor-risk patient population. METHODS: In this study, the authors retrospectively analyzed the efficacy and toxicity of 2-CdA with cyclophosphamide combination (the CC regimen) in 20 patients with previously untreated B-cell CLL who had 17p13.1 deletion reported to the Polish Adult Leukemia Group (PALG) registry. The CC regimen consisted of 2-CdA at a dose of 0.12 mg/kg and cyclophosphamide at a dose of 250 mg/m2 given intravenously for 3 consecutive days. The CC cycles were repeated at 28-day intervals for up to 6 cycles. RESULTS: Overall, 16 of 20 patients (80%) responded to CC therapy, including 10 patients (50%) who obtained a complete response and 6 patients (30%) who obtained a partial response. The median progression-free survival reached 23 months (95% confidence interval, 5-41 months). The overall survival probability at 2 years was 52.5% (95% confidence interval, 26%-79%). Treatment toxicity generally was acceptable. Infections were the most common grade 3/4 complications and occurred in 6 patients (30%). CONCLUSIONS: In this retrospective analysis, the results demonstrated that the CC regimen produced a relatively high response rate in patients with previously untreated CLL who had 17p13.1/TP53 deletion, although the response duration and survival were not satisfactory. It is possible that a combination of the CC regimen with p53-independent agents may improve treatment results in this poor-risk patient population. Cancer 2009. © 2008 American Cancer Society. [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] Ifosfamide/carboplatin/etoposide (ICE) as front-line, topotecan/ cyclophosphamide as second-line and oral temozolomide as third-line treatment for advanced neuroblastoma over one year of ageACTA PAEDIATRICA, Issue 2004A Donfrancesco Children affected by advanced neuroblastoma have a discouraging prognosis, but intensive induction chemotherapy may increase the complete response rate. The combination of ifosfamide, carboplatin and etoposide (ICE) was used for the first time as front-line regimen in patients with stage 4 neuroblastoma over the age of 1 y. Similarly, second-line treatment for children with relapsed neuroblastoma, particularly after high-dose chemotherapy, has been unsatisfactory. The combination of topotecan and cyclophosphamide was studied in resistant or relapsed solid tumors. Furthermore, there is a need for effective palliative treatment in patients failing therapy. Temozolomide, a new dacarbazine analog with optimal oral bioavailability, is being used in an ongoing phase II study as an alternative to oral etoposide. Seventeen patients with stage 4 neuroblastoma have entered the ICE study; 15/16 (94%) major responses after induction were observed and 6/16 (37%) evaluable patients are disease free after a median of 51 mo. Twenty-one patients with relapsed/refractory disease (of whom 13 neuroblastomas) entered the topotecan/cyclophosphamide study: 7/21 (33%) patients responded. Forty-one patients entered the temozolomide study (of whom 16 had neuroblastomas): stable disease and symptom relief were obtained in 15/30 (50%) evaluable patients. Intensive induction with ICE resulted in a faster response with high response rate; a larger study with longer follow-up is needed to confirm a survival advantage. Second-line treatment was effective in obtaining remissions, some of them long lasting. Third-line treatment did not elicit measurable responses in neuroblastoma, but achieved prolonged freedom from disease progression and excellent palliation in several patients. [source] Genetic determinants for activated fluoropyrimidine chemotherapyDRUG DEVELOPMENT RESEARCH, Issue 2 2006William H. GmeinerArticle first published online: 5 JUN 200 Abstract Fluoropyrimidines (FPs) remain widely used for the treatment of diverse malignancies more than four decades following the initial report of 5-fluorouracil (5FU), the archetypal FP, as a novel compound with potential anti-neoplastic activity. Subsequent decades of research have enriched our understanding of the biochemical mechanisms that are important for FP activation as well as the genetic determinants that are predictive of the likely success, or failure, of FP chemotherapy for a particular individual. The concept that chemotherapy should be customized to complement the genetic profiles of cancer patients has become increasingly important as genotyping of tumor samples has become possible and as the number of available anticancer drugs has increased. Significant progress has been made in identifying the gene expression profiles for cancer patients who are likely to benefit from treatment with FPs. In this review, we will summarize the results of retrospective clinical studies correlating response to FP chemotherapy with the expression of specific genes, such as TS and DPD. We will also present a summary of FPs in current clinical use, including orally bioavailable FPs such as capecitabine, as well as FPs that are in pre-clinical development, such as FdUMP[10]. Refinement of a target population through pharmacogenetic analysis and development of novel FPs that evoke very high response rates in this target population will likely result in the use of FP regimens in the coming era when cancer becomes a largely manageable disease. Drug Dev. Res. 67:119,129, 2006. © 2006 Wiley-Liss, Inc. [source] Isolated limb infusion: A reviewJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2009Hidde M. Kroon MD Abstract Isolated limb perfusion is the preferred treatment option for locally advanced melanoma and sarcoma confined to a limb. This treatment results in high response rates with a satisfying duration of response in both tumours. A drawback of isolated limb perfusion, however, is the invasive and complex character of the procedure. Isolated limb infusion has been designed as a minimally invasive alternative to isolated limb perfusion. Treatment results of this simple technique, reported by various centres worldwide, show comparable response rates for melanoma and sarcoma. Therefore isolated limb infusion may replace isolated limb perfusion in the future as the preferred treatment option for these locally advanced limb tumours. J. Surg. Oncol. 2009;100:169,177. © 2009 Wiley-Liss, Inc. [source] Efficacy and Safety of Tadalafil 20 mg on Demand vs.THE JOURNAL OF SEXUAL MEDICINE, Issue 8 2010Tadalafil 5 mg Once-a-Day in the Treatment of Post-Radiotherapy Erectile Dysfunction in Prostate Cancer Men: A Randomized Phase II Trial ABSTRACT Introduction., The role of phosphodiesterase type 5 inhibitors in the treatment of post-radiotherapy erectile dysfunction (ED) has not been extensively investigated. Aim., To compare the efficacy and safety of on-demand 20-mg tadalafil (arm A) with the newly released tadalafil 5-mg once-a-day dosing (arm B) in patients with ED following radiotherapy for prostate cancer (PC). Methods., Randomized study to receive on-demand 20-mg or once-a-day 5-mg tadalafil for 12 weeks. Main Outcome Measures., Changes in the International Index of Erectile Function (IIEF) domain scores and Sexual Encounter Profile (SEP) question 2 and 3 positive response rates. Results., Fifty-two out of 86 screened patients were randomized. Forty-four patients were evaluable for efficacy. A significant improvement in all domains of the IIEF was observed in both arms (P = 0.0001) with mean erectile function domain scores values of 25 and 27.1 for the 20-mg and 5-mg tadalafil, respectively (P = 0.19). SEP 2 and 3 positive response rates increased from 0% in both arms at baseline to 81% and 70% in the 20-mg arm and 90% and 73% in the 5-mg arm, respectively, at the end of treatment (P = 0.27). End of treatment global efficacy question positive answers were 86% in the 20-mg arm and 95% in the 5-mg arm (P = 0.27). Higher treatment compliance was shown in arm B (100%) as compared with arm A (86%). There was a nonstatistically significant trend toward fewer side effects in favor of the 5-mg daily dose arm. Conclusions., In the study population, both tadalafil formulations generated significantly high response rates according to the outcome measures and were well tolerated. The once-a-day 5-mg dosing showed higher compliance and marginally reduced side effects, thus making it an attractive alternative to on-demand therapy for ED in post-radiotherapy PC patients. Ricardi U, Gontero P, Ciammella P, Badellino S, Valentino F, Munoz F, Guarneri A, Rondi N, Moretto F, Filippi AR, Ragona R, and Tizzani A. Efficacy and safety of tadalafil 20 mg on demand vs. tadalafil 5 mg once-a-day in the treatment of post-radiotherapy erectile dysfunction in prostate cancer men: A randomized phase II trial. J Sex Med 2010;7:2851,2859. [source] | ||||||||||