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ABSTRACT: To evaluate the effect of Bevacizumab in combination with chemotherapy on overall survival of patients with metastatic solid tumors.
A systematic literature search to identify randomized trials comparing chemotherapy with and without Bevacizumab in metastatic cancer. The primary end point was overall survival (OS) and the secondary end points were progression free survival (PFS) and toxicity. A meta-analysis was performed for each tumor type and for the combination of all tumors.
24 randomized trials with 8 different types of malignancies were included in this meta-analysis. Patients treated with Bevacizumab had an OS benefit, hazard ratio (HR) 0.89 (95% CI 0.84-0.93, P<0.00001 I(2)-4%). The combined analysis showed a PFS benefit with a HR 0.71 (95% CI 0.68-0.74, P<0.00001, I(2)-54%). The toxicity analysis showed a statistically significant increase in fatal adverse events (FAEs) in the Bevacizumab treatment arm, risk ratio (RR) 1.47 (95% CI 1.1-1.98). A separate analysis of the lung cancer trials showed an increased risk of fatal pulmonary hemorrhage with a RR of 5.65 (95% CI 1.26-25.26). The risk of G3-4 adverse events was increased: RR 1.2 (95% CI 1.15-1.24).
in this combined analysis Bevacizumab improved OS (with little heterogeneity) and PFS. These results should be considered in the light of lack of markers predictive of response and the increased severe and fatal toxicity seen with Bevacizumab treatment.
PLoS ONE 01/2013; 8(1):e51780. · 4.09 Impact Factor
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ABSTRACT: Acute promyelocytic leukemia (APL) is the most curable type of leukemia. A consensus exists regarding the need for administration of both induction and consolidation treatments, albeit using different approaches. However, there is conflicting evidence for the role of maintenance treatment in APL patients.
To examine the efficacy and safety of maintenance therapy in APL patients and to establish the optimal regimen for maintenance.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1966 to July 2012), LILACS (1982 to July 2012), relevant conference proceedings (2000 to 2012) and databases of ongoing and unpublished trials.
Randomized controlled trials assessing maintenance treatment in patients with newly diagnosed APL in first complete remission (CR) following induction or induction and consolidation therapy.
Two review authors assessed the quality of trials and extracted data. We estimated and pooled hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI) using the fixed-effect model. If significant heterogeneity was present we explored potential causes for such heterogeneity and if not found we used also the random-effects model.
We included 10 randomized controlled trials enrolling 2072 patients in the systematic review, and conducted meta-analysis on nine of them. There was no statistically significant effect on overall survival (OS) in the three main comparisons (HR for any maintenance treatment versus observation 0.79, 95% CI 0.49 to 1.27; HR for all-trans retinoic acid (ATRA)-based maintenance versus non-ATRA based maintenance 1.21, 95% CI 0.73 to 1.98; HR for ATRA alone maintenance versus ATRA and chemotherapy 0.99, 95% CI 0.69 to 1.43). However, disease free survival (DFS) was improved with any maintenance therapy compared to observation (HR 0.59, 95% CI 0.48 to 0.74; 5 trials, 1209 patients) and with ATRA and chemotherapy compared to ATRA alone maintenance (HR for ATRA alone compared to ATRA and chemotherapy 1.38, 95% CI 1.09 to 1.76; 4 trials, 1028 patients). DFS was not improved with ATRA-based regimens compared to non-ATRA based regimens (HR 0.72, 95% CI 0.51 to 1.01; 4 trials, 670 patients). Analysis of clinically relevant adverse events could not be conducted due to paucity of data. Yet, increased reports of grade 3/4 adverse events were noted for any maintenance versus observation and for combined ATRA and chemotherapy versus ATRA alone treatment. The major limitation of this review lies in the variability between the included trials in both maintenance and pre-maintenance parameters. We tried to address this variability and to reduce its potential biases by conducting three separate main comparisons, as outlined above, leaving less statistical power to the presented results.
Maintenance therapy compared to observation in APL patients improved DFS but not OS. Similarly, ATRA and chemotherapy compared to ATRA improved DFS but not OS. In contrast, ATRA based regimens compared to non-ATRA based regimens did not demonstrate a survival benefit. The significance of these findings is limited due to clinical heterogeneity between studies.
Cochrane database of systematic reviews (Online) 01/2013; 3:CD009594. · 5.72 Impact Factor
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ABSTRACT: Primary Burkitt's lymphoma of the ovary is extremely rare. We report the case of a 39-year-old woman who presented with a 1-month history complaints of night sweats, abdominal pain and dyspnea. Physical examination demonstrated pleural effusions, ascites and an abdominal mass. Imaging showed enlargement of both ovaries extending to the surrounding tissue. Frozen sections on explorative laparotomy suggested granulosa cell tumor of the ovary, and thus extensive debulking was carried out. The final pathological report was compatible with Burkitt's lymphoma. A systematic literature review revealed another 16 cases of ovarian Burkitt's lymphoma. Characteristics predictive for the diagnosis of Burkitt's lymphoma were: younger age, bilateral ovarian involvement, a rapidly progressive course and high LDH levels.
Acta Haematologica 12/2012; 129(3):169-174. · 1.35 Impact Factor
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ABSTRACT: Induction therapy in patients with multiple myeloma has evolved from chemotherapy-based to novel agents-based regimens. We compared autologous hematopoietic cell transplantation (HCT)-associated toxicity in patients induced with VTD-PACE (bortezomib, thalidomide, dexamethasone, cisplatinum, adriamycin, cyclophosphamide, and etoposide) to that of patients induced with novel agents-only therapy.
We reviewed medical charts of all patients with multiple myeloma who were given induction therapy and HCT.
Between the years 2007 and 2011, 38 patients received VTD-PACE, and 31 patients received novel agents-only regimen. Mean time to neutrophil and platelets recovery was longer in patients given VTD-PACE compared with those given novel agents-only regimen (7 vs. 6 d, p = 0.0002 and 11 vs. 10 d, p = 0.04, respectively). We observed higher rates of grade 2-4 mucositis and parenteral narcotic analgesia administration in the patients given VTD-PACE (45% vs. 19%, p = 0.05 and 37% vs. 12%, p = 0.07, respectively). Progression free survival and overall survival were not statistically significantly different between the two groups.
A more intensive induction regimen was associated with slightly delayed counts recovery and a higher rate of mucositis during HCT compared with novel agents-only regimens. A longer follow-up is needed to assess long-term disease control of the two different regimens.
Clinical Transplantation 09/2012; 26(5):E549-54. · 1.67 Impact Factor
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ABSTRACT: Background: Current guidelines are inconclusive regarding intravenous (IV) iron for treatment of chemotherapy-induced anaemia (CIA). Material and methods: Systematic review and meta-analysis of randomised controlled trials comparing IV iron with no iron or oral iron for treatment of chemotherapy induced anaemia (CIA). Primary outcomes: haematopoietic response and red blood cell (RBC) transfusion requirements. For dichotomous data, relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. For continuous data, weighted mean differences were calculated. Results: Eleven trials included 1681 patients, the majority examining the addition of IV iron to erythropoiesis stimulating agents (ESA) (1562 patients, 92.9%). IV iron significantly increased haematopoietic response rate [RR 1.28 (95% CI 1.125-1.45), seven trials with ESA] and decreased the rate of blood transfusions both in trials with ESA [RR 0.76 (95% CI 0.61-0.95), seven trials] and without ESA [RR 0.52 (95% CI 0.34-0.80)]. The increase in haematopoietic response rate correlated with total IV iron dose, regardless of baseline iron status. Mortality and safety profile was comparable between groups. Conclusions: IV iron added to ESA results in an increase in haematopoietic response and reduction in the need for RBC transfusions, with no difference in mortality or adverse events.
Acta oncologica (Stockholm, Sweden) 08/2012; · 2.27 Impact Factor
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ABSTRACT: Background: Second generation tyrosine kinase inhibitors have been introduced recently as first-line treatment for chronic phase-chronic myelogenous leukemia. We aimed to evaluate the efficacy and safety of second generation tyrosine kinase inhibitors vs. imatinib as first-line treatment for these patients. Design and Methods: Systematic review and meta-analysis of randomized controlled trials comparing second generation tyrosine kinase inhibitors to imatinib as first-line treatment in chronic phase-chronic myelogenous leukemia patients. Outcomes assessed were: complete cytogenetic response and major molecular response at 12, 18 and 24 months; all-cause mortality and progression to accelerated phase/blastic crisis at 12, 18 and 24 months and chronic myelogenous leukemia related mortality and toxicity on last follow-up. Relative risks were estimated and pooled using a fixed effect model. Results: Our search yielded four trials including 2120 patients. At 12 months, treatment with second generation tyrosine kinase inhibitors significantly improved both complete cytogenetic response and major molecular response, [Relative risk 1.16, 95% CI 1.09 to 1.23 and relative risk 1.68, 95% CI, 1.48 to 1.91, respectively]. While major molecular response was improved at all-time points, complete cytogenetic response improved at 18 months but not at 24 months. Importantly, rate of progression to accelerated phase / blastic crisis was significantly lower with the newer tyrosine kinase inhibitors throughout all time points. Second generation tyrosine kinase inhibitors improved chronic myelogenous leukemia related mortality without a statistically significant difference in all-cause mortality at 12, 18 and 24 months. Conclusions: Second generation tyrosine kinase inhibitors can be added safely to the first-line treatment armamentarium of chronic phase-chronic myelogenous leukemia patients. Although an advantage is suggested by surrogate parameters, longer follow-up is necessary to see if this translates into superior overall survival.
Haematologica 08/2012; · 6.42 Impact Factor
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ABSTRACT: Surveys of bacterial infections among neutropenic cancer patients frequently report pooled antibiotic susceptibility data. Management guidelines address initial antibiotic regimens for febrile neutropenia. In this study, rates of bacterial infection and antibiotic susceptibilities among initial and subsequent or breakthrough episodes of fever were analysed. Prospective surveillance of fever of unknown origin (FUO), clinically documented infection and microbiologically documented infection (MDI) was conducted in the haemato-oncology and haematopoietic stem cell transplantation wards in a single cancer centre in Israel. Subsequent infections were defined as those developing during or after broad-spectrum antibiotic treatment. A total of 567 febrile episodes were documented among 271 patients. Bacterial MDIs were documented in 104/162 (64%) initial febrile episodes and 75/405 (19%) subsequent episodes and Gram-negative bacteria predominated (64% and 71%, respectively). Escherichia coli was the most common species isolated. Higher antibiotic susceptibilities were observed for initial compared with subsequent MDIs for Gram-negative bacteria [ceftazidime 80% vs. 45%, piperacillin/tazobactam (TZP) 86% vs. 40% and meropenem 95% vs.76%] and Gram-positive bacteria. TZP monotherapy was the most commonly used antibiotic and its susceptibility decreased to 22.2% following its use. Appropriate empirical antibiotic treatment was administered in 71/97 (73%) initial and 40/74 (54%) subsequent episodes (P=0.009) and was significantly associated with mortality (adjusted odds ratio=0.4, 95% confidence interval 0.18-0.87). We conclude that previous antibiotic exposure significantly impacts antibiotic susceptibility and that pooled reporting of all infections can be misleading. Treatment guidelines should address the antibiotic treatment of breakthrough fever.
International journal of antimicrobial agents 06/2012; 40(2):123-6. · 3.03 Impact Factor
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ABSTRACT: Survival of adults with acute lymphoblastic leukemia (ALL) is inferior to that of pediatric patients. Strategies to improve the outcome of adult population are warranted. This study aims to evaluate the efficacy and safety of pediatric-inspired regimens given to adolescents and young adults (AYA), usually defined as 16-39 years, with ALL. Systematic review and meta-analysis of comparative trials of AYA patients with ALL given induction chemotherapy with either pediatric-inspired regimens or conventional-adult chemotherapy was conducted. Relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. Our search yielded 11 trials, including 2,489 patients. AYA patients given pediatric-inspired regimens had a statistically significant lower all cause mortality rate at 3 years (RR 0.58; 95% CI 0.51-0.67). Complete remission rate after induction chemotherapy and event free survival were superior in the pediatric-inspired regimens arm (RR 1.05; 95% CI 1.01-1.10 and RR 1.66; 95% CI 1.39-1.99, respectively). Relapse rate was also lower in patients given pediatric-inspired regimens (RR 0.51; 95% CI 0.39-0.66) with comparable nonrelapse mortality between the two groups (RR 0.53, 95% CI 0.19-1.48). Pediatric-inspired regimens are superior to conventional-adult chemotherapy in AYA ALL patients. Further randomized controlled studies to investigate this approach in adult ALL patients are warranted.
American Journal of Hematology 02/2012; 87(5):472-8. · 4.67 Impact Factor
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ABSTRACT: Acute myelogenous leukemia (AML) is a fatal bone marrow cancer. Colony-stimulating factors (CSFs) are frequently administered during and after chemotherapy to reduce complications. However, their safety with regard to disease-related outcomes and survival in AML is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the impact of CSFs on patient outcomes, including survival.
To assess the safety/efficacy of CSFs with regard to disease-related outcomes and survival in patients with AML.
We conducted a comprehensive search strategy. We identified relevant randomized clinical trials by searching the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 7), MEDLINE (January 1966 to July 2010), LILACS (up to December 2009), databases of ongoing trials and relevant conference proceedings.
Randomized controlled trials that compared the addition of CSFs during and following chemotherapy to chemotherapy alone in patients with AML. We excluded trials evaluating the role of CSFs administered for the purpose of stem cell collection and/or priming (e.g. before and/or only for the duration of chemotherapy).
Two review authors appraised the quality of trials and extracted data. For each trial, we expressed results as relative risk (RR) with 95% confidence intervals (CI) for dichotomous data. We analyzed time-to-event outcomes as hazard ratios (HRs).
The search yielded 19 trials including 5256 patients. The addition of CSFs to chemotherapy yielded no difference in all-cause mortality at 30 days and at the end of follow up (RR 0.97; 95% CI 0.80 to 1.18 and RR 1.01; 95% CI 0.98 to 1.05, respectively) or in overall survival (HR 1.00; 95% 0.93 to 1.08). There was no difference in complete remission rates (RR 1.03; 95% CI 0.99 to 1.07), relapse rates (RR 0.97; 95% CI 0.89 to 1.05) and disease-free survival (HR 1.00; 95% CI 0.90 to 1.13). CSFs did not decrease the occurrence of bacteremias (RR 0.96; 95% CI 0.82 to 1.12), nor the occurrence of invasive fungal infections (RR 1.40; 95% CI 0.90 to 2.19). CSFs marginally increased adverse events requiring discontinuation of CSFs as compared to the control arm (RR 1.33; 95% CI 1.00 to 1.56).
In summary, colony-stimulating factors should not be given routinely to acute myelogenous leukemia patients post-chemotherapy since they do not affect overall survival or infectious parameters including the rate of bacteremias and invasive fungal infections.
Cochrane database of systematic reviews (Online) 01/2012; 6:CD008238. · 5.72 Impact Factor
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ABSTRACT: Indolent B cell lymphoid malignancies include follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma and marginal zone lymphomas. Chronic lymphocytic leukaemia (CLL) is a lymphoid malignancy similar to small lymphocytic lymphoma (SLL) in its leukaemic phase.Indolent lymphoid malignancies including CLL are characterised by slow growth, a high initial response rate and a relapsing and progressive disease course. Advanced-stage indolent B cell lymphoid malignancies are often incurable. If symptoms or progressive disease occur, chemotherapy plus rituximab is indicated. No chemotherapy regimen has been shown to improve overall survival compared to a different regimen.Bendamustine is efficacious in the treatment of patients with indolent B cell lymphoid malignancies. A number of randomised controlled trials have examined the effect of bendamustine compared to other chemotherapy regimens in these patients. Improved disease control with no survival benefit is shown.
To evaluate the efficacy of bendamustine therapy for patients with indolent B cell lymphoid malignancies including CLL.
We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2), MEDLINE (1966 to May 2012), EMBASE (1974 to November 2011), LILACS (1982 to May 2012), databases of ongoing trials (accessed 30 April 2012) and relevant conference proceedings. We searched references of identified trials and contacted the first author of each included trial.
Randomised controlled trials that compared a bendamustine-containing regimen to other chemotherapy with or without immunotherapy.
Two authors independently appraised the quality of each trial and extracted data from included trials. We estimated and pooled hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI).
We included five trials randomising 1343 adult patients in the systematic review. Allocation and blinding were unclear in three trials and adequate in two. Incomplete outcome data and selective reporting were adequate in all trials. Trials varied in the type of lymphoid malignancy, bendamustine regimen and the comparator regimen. In the three trials that included patients with follicular lymphoma, mantle cell lymphoma and other indolent lymphomas the comparator treatment was cyclophosphamide, a combination of cyclophosphamide, vincristine, doxorubicin and prednisone, and fludarabine. Two trials included only patients with CLL and compared bendamustine to chlorambucil, and to fludarabine. We did not conduct a meta-analysis due to the clinical heterogeneity among trials. Bendamustine had no statistically significant effect on the overall survival of patients with indolent B cell lymphoid malignancies in any of the included trials (trials of moderate quality). Progression-free survival was statistically significantly improved with bendamustine treatment compared to other chemotherapy in three of the four trials that reported on it. One trial demonstrated a non statistically significant improvement of PFS. The risk of grade 3 or 4 adverse events was similar when bendamustine was compared to CHOP and fludarabine, and higher when compared to chlorambucil. Compared to chlorambucil quality of life was unaffected by bendamustine treatment (one trial, no meta-analysis).
As none of the currently available chemotherapeutic protocols for induction therapy in indolent B cell lymphoid malignancies confer a survival benefit and due to the improved progression-free survival in each of the included trials, and a similar rate of grade 3 or 4 adverse events, bendamustine may be considered for the treatment of patients with indolent B cell lymphoid malignancies. However, the unclear effect on survival and the higher rate of adverse events compared to chlorambucil in patients with CLL/SLL does not support the use of bendamustine for these patients.The effect of bendamustine combined with rituximab should be evaluated in randomised clinical trials with more homogenous populations and outcomes for specific subgroups of patients by type of lymphoma should be reported. Any future trial should evaluate the effect of bendamustine on quality of life.
Cochrane database of systematic reviews (Online) 01/2012; 9:CD009045. · 5.72 Impact Factor
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ABSTRACT: Bacterial infections are a major cause of morbidity and mortality in patients who are neutropenic following chemotherapy for malignancy. Trials have shown the efficacy of antibiotic prophylaxis in reducing the incidence of bacterial infections but not in reducing mortality rates. Our systematic review from 2006 also showed a reduction in mortality.
This updated review aimed to evaluate whether there is still a benefit of reduction in mortality when compared to placebo or no intervention.
We searched the Cochrane Cancer Network Register of Trials (2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), abstracts of conference proceedings and the references of identified studies.
Randomised controlled trials (RCTs) or quasi-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention, or another antibiotic, to prevent bacterial infections in afebrile neutropenic patients.
Two authors independently appraised the quality of each trial and extracted data from the included trials. Analyses were performed using RevMan 5.1 software.
One-hundred and nine trials (involving 13,579 patients) that were conducted between the years 1973 to 2010 met the inclusion criteria. When compared with placebo or no intervention, antibiotic prophylaxis significantly reduced the risk of death from all causes (46 trials, 5635 participants; risk ratio (RR) 0.66, 95% CI 0.55 to 0.79) and the risk of infection-related death (43 trials, 5777 participants; RR 0.61, 95% CI 0.48 to 0.77). The estimated number needed to treat (NNT) to prevent one death was 34 (all-cause mortality) and 48 (infection-related mortality).Prophylaxis also significantly reduced the occurrence of fever (54 trials, 6658 participants; RR 0.80, 95% CI 0.74 to 0.87), clinically documented infection (48 trials, 5758 participants; RR 0.65, 95% CI 0.56 to 0.76), microbiologically documented infection (53 trials, 6383 participants; RR 0.51, 95% CI 0.42 to 0.62) and other indicators of infection.There were no significant differences between quinolone prophylaxis and TMP-SMZ prophylaxis with regard to death from all causes or infection, however, quinolone prophylaxis was associated with fewer side effects leading to discontinuation (seven trials, 850 participants; RR 0.37, 95% CI 0.16 to 0.87) and less resistance to the drugs thereafter (six trials, 366 participants; RR 0.45, 95% CI 0.27 to 0.74).
Antibiotic prophylaxis in afebrile neutropenic patients significantly reduced all-cause mortality. In our review, the most significant reduction in mortality was observed in trials assessing prophylaxis with quinolones. The benefits of antibiotic prophylaxis outweighed the harm such as adverse effects and the development of resistance since all-cause mortality was reduced. As most trials in our review were of patients with haematologic cancer, we strongly recommend antibiotic prophylaxis for these patients, preferably with a quinolone. Prophylaxis may also be considered for patients with solid tumours or lymphoma.
Cochrane database of systematic reviews (Online) 01/2012; 1:CD004386. · 5.72 Impact Factor
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12/2011; , ISBN: 978-953-307-553-2
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ABSTRACT: In a previous systematic review and meta-analysis of five randomized controlled trials comparing rituximab maintenance with no maintenance (observation or rituximab at progression) for patients with follicular lymphoma, we reported that rituximab maintenance treatment improved the overall survival of patients. In this study, we did a similar search of the electronic databases updated through December 31, 2010, and included nine trials and 2586 follicular lymphoma patients. Hazard ratios (HRs) for time-to-event data were estimated and pooled using the inverse variance method. Risk ratios for dichotomous data were pooled using a fixed effect model. Patients treated with rituximab maintenance had improved overall survival (pooled HR of death = 0.76, 95% confidence interval [CI] = 0.62 to 0.92) compared with patients in the no maintenance group. Patients with refractory or relapsed (ie, previously treated) follicular lymphoma treated with rituximab maintenance had improved overall survival (pooled HR of death = 0.72, 95% CI = 0.57 to 0.91), whereas previously untreated patients had no survival benefit (pooled HR of death = 0.86, 95% CI = 0.60 to 1.25). The rate of infection-related adverse events was higher in the rituximab maintenance group (pooled risk ratio = 1.67, 95% CI = 1.40 to 2.00). These results further support the use of rituximab maintenance in the standard of care for refractory or relapsed follicular lymphoma.
CancerSpectrum Knowledge Environment 12/2011; 103(23):1799-806. · 14.07 Impact Factor
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ABSTRACT: Imatinib at a dose of 400 mg daily is considered frontline treatment in chronic phase chronic myeloid leukemia (CP-CML). We conducted a systematic review and meta-analysis of randomized controlled trials comparing frontline treatment with imatinib 400 mg daily versus higher doses (≥600 mg daily) in patients with CP-CML. The search yielded four trials, randomizing 1,673 patients. At 12 months, high dose compared with standard dose imatinib improved complete cytogenetic response (CCyR) (RR 1.17, 95% CI 1.08-1.26, four trials, I(2) = 33%) as well as major molecular response (MMolR) (RR 1.26, 95% CI 1.12-1.42, four trials, I(2) = 0%). There was no difference in all-cause mortality or disease progression at the end of follow up. Adverse events requiring discontinuation were more common in the high-dose arm (RR 1.98, 95% CI 1.20-3.26, three trials, I(2) = 0%), as were Grade III/IV neutropenia and thrombocytopenia: RR 1.56, 95% CI 1.15-2.12 and RR 1.86, 95% CI 1.28-2.70, respectively. There is currently insufficient evidence to support the routine use of higher doses of imatinib as frontline treatment for CP-CML. Extended follow up is needed to evaluate if the superior CCyR and MMolR with higher doses of imatinib will translate to long-term clinical benefit.
American Journal of Hematology 08/2011; 86(8):657-62. · 4.67 Impact Factor
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ABSTRACT: Acute myelogenous leukemia (AML) is a fatal bone marrow cancer. Colony-stimulating factors (CSFs) are frequently administered during and after chemotherapy to reduce complications. However, their safety with regard to disease-related outcomes and survival in AML is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the impact of CSFs on patient outcomes, including survival.
To assess the safety/efficacy of CSFs with regard to disease-related outcomes and survival in patients with AML.
We conducted a comprehensive search strategy. We identified relevant randomized clinical trials by searching the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 7), MEDLINE (January 1966 to July 2010), LILACS (up to December 2009), databases of ongoing trials and relevant conference proceedings.
Randomized controlled trials that compared the addition of CSFs during and following chemotherapy to chemotherapy alone in patients with AML. We excluded trials evaluating the role of CSFs administered for the purpose of stem cell collection and/or priming (e.g. before and/or only for the duration of chemotherapy).
Two review authors appraised the quality of trials and extracted data. For each trial, we expressed results as relative risk (RR) with 95% confidence intervals (CI) for dichotomous data. We analyzed time-to-event outcomes as hazard ratios (HRs).
The search yielded 19 trials including 5256 patients. The addition of CSFs to chemotherapy yielded no difference in all-cause mortality at 30 days and at the end of follow up (RR 0.97; 95% CI 0.80 to 1.18 and RR 1.01; 95% CI 0.98 to 1.05, respectively) or in overall survival(HR 1.00; 95% 0.93 to 1.08). There was no difference in complete remission rates(RR 1.03; 95% CI 0.99 to 1.07), relapse rates(RR 0.97; 95% CI 0.89 to 1.05) and disease-free survival(HR 1.00; 95% CI 0.90 to 1.13). CSFs did not decrease the occurrence of bacteremias(RR 0.96; 95% CI 0.82 to 1.12), nor the occurrence of invasive fungal infections(RR 1.40; 95% CI 0.90 to 2.19). CSFs marginally increased adverse events requiring discontinuation of CSFs as compared to the control arm(RR 1.33; 95% CI 1.00 to 1.56).
The addition of CSFs to chemotherapy does not adversely influence all-cause mortality, complete remission or relapse rates in patients with AML. Although the benefit of CSFs is limited to reduction of neutropenic and febrile days, they can be administered safely when necessary.
Cochrane database of systematic reviews (Online) 01/2011; · 5.72 Impact Factor
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ABSTRACT: The course of follicular lymphoma has changed considerably with the introduction of immunotherapy. Systematic reviews and meta-analyses are reliable, efficient and well-established methods to summarize the vast amount of data acquired in recent years on the role of immunotherapy, including monoclonal antibodies, radio-labeled monoclonal antibodies and interferon-α in the treatment of patients with follicular lymphoma. We aimed to summarize the data from systematic reviews assessing immunotherapy for these patients. A search through Medline and the Cochrane Library for systematic reviews of randomized controlled trials of different types of immunotherapy for patients with follicular lymphoma yielded 17 reviews. Eleven of them were eligible for this review and are described herein. These systematic reviews have dramatically influenced the approach to patients with follicular lymphoma.
Acta Haematologica 01/2011; 125(1-2):23-31. · 1.35 Impact Factor
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ABSTRACT: Dose-dense chemotherapy has become a mainstay regimen in the adjuvant setting for women with high-risk breast cancer. We performed a systematic review and meta-analysis of the existing data from randomized controlled trials regarding the efficacy and toxicity of the dose-dense chemotherapy approach in nonmetastatic breast cancer.
Randomized controlled trials that compared a dose-dense chemotherapy protocol with a standard chemotherapy schedule in the neoadjuvant or adjuvant setting in adult women older than 18 years with breast cancer were identified by searching The Cochrane Cancer Network register of trials, The Cochrane Library, and LILACS and MEDLINE databases (from January 1966 to January 2010). Hazard ratios (HRs) of death and recurrence and relative risks of adverse events were estimated and pooled. All statistical tests were two-sided.
Ten trials met the inclusion criteria and were classified into two categories based on trial methodology. Three trials enrolling 3337 patients compared dose-dense chemotherapy with a conventional chemotherapy schedule (similar agents). Patients who received dose-dense chemotherapy had better overall survival (HR of death = 0.84, 95% confidence interval [CI] = 0.72 to 0.98, P = .03) and better disease-free survival (HR of recurrence or death = 0.83, 95% CI = 0.73 to 0.94, P = .005) than those on the conventional schedule. No benefit was observed in patients with hormone receptor-positive tumors. Seven trials enrolling 8652 patients compared dose-dense chemotherapy with regimens that use standard intervals but with different agents and/or dosages in the treatment arms. Similar results were obtained for these trials with respect to overall survival (HR of death = 0.85, 95% CI = 0.75 to 0.96, P = .01) and disease-free survival (HR of recurrence or death = 0.81, 95% CI = 0.73 to 0.88, P < .001). The rate of nonhematological adverse events was higher in the dose-dense chemotherapy arms than in the conventional chemotherapy arms.
Dose-dense chemotherapy results in better overall and disease-free survival, particularly in women with hormone receptor-negative breast cancer. However, additional data from randomized controlled trials are needed before dose-dense chemotherapy can be considered as the standard of care.
CancerSpectrum Knowledge Environment 12/2010; 102(24):1845-54. · 14.07 Impact Factor
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ABSTRACT: The optimal postremission therapy in adults with acute lymphoblastic leukemia (ALL) is still a matter of debate. The objective of this study was to compare the various potential therapeutic options for patients who achieved first complete remission.
The authors conducted a systematic review and meta-analysis of randomized trials, including patients with standard-risk (SR) All and high-risk (HR) ALL who received first postremission therapy. Outcomes assessed were all-cause mortality (ACM), disease recurrence (relapse), and nonrelapse mortality (NRM). Relative risks (RRs) with 95% confidence intervals (CIs) were estimated and pooled.
Overall, there was a significant reduction in ACM in the allogenic stem cell transplantation (alloSCT) arm (RR, 0.88; 95% CI, 0.8-0.97) compared with autologous stem cell transplantation (ASCT) or chemotherapy. Subgroup analyses revealed a similar pattern among SR patients (RR, 0.8; 95% CI, 0.68-0.94) but a nonsignificant advantage for alloSCT among HR patients (RR, 0.88; 95% CI, 0.76-1.01). There was an increase in NRM (RR, 2.99; 95% CI, 1.37-6.53) and a decrease in the relapse rate in the alloSCT arm (RR, 0.52; 95% CI, 0.33-0.83). There was no difference in ACM or the relapse rate between the ASCT and chemotherapy arms.
Overall, alloSCT was superior to ASCT or chemotherapy for patients with ALL in first complete remission. The survival advantage was of greater statistical significance for patients with SR ALL than for patients with HR ALL.
Cancer 07/2010; 116(14):3447-57. · 4.77 Impact Factor
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Nature Reviews Clinical Oncology 03/2010; 7(3):1; author reply 1. · 11.96 Impact Factor
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Haematologica 02/2010; 95(2):343-4. · 6.42 Impact Factor
