LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 14

Search options

  1. Article ; Online: WITHDRAWN: Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma.

    Sasse, Andre D / Sasse, Emma C / Clark, Luciana Go / Clark, Otavio Augusto Camara

    The Cochrane database of systematic reviews

    2018  Volume 2, Page(s) CD005413

    Abstract: Background: Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected ... ...

    Abstract Background: Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected people, because melanoma does not respond to most systemic treatments. A number of novel approaches are under evaluation and have shown promising results, but they are usually associated with increased toxicity and cost. The combination of chemotherapy and immunotherapy has been reported to improve treatment results, but it is still unclear whether evidence exists to support this choice, compared with chemotherapy alone. No language restrictions were imposed.
    Objectives: To compare the effects of therapy with chemotherapy and immunotherapy (chemoimmunotherapy) versus chemotherapy alone in people with metastatic malignant melanoma.
    Search methods: We searched the Cochrane Skin Group Specialised Register (14 February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to 30 January 2006 ), EMBASE (2003 to 20 July 2005) and LILACS (1982 to 20 February 2006). References, conference proceedings, and databases of ongoing trials were also used to locate trials.
    Selection criteria: All randomised controlled trials that compared the use of chemotherapy versus chemoimmunotherapy on people of any age, diagnosed with metastatic melanoma.
    Data collection and analysis: Two authors independently assessed each study to determine whether it met the pre-defined selection criteria, with differences being resolved through discussion with the review team. Two authors independently extracted the data from the articles using data extraction forms. Quality assessment included an evaluation of various components associated with biased estimates of treatment effect. Whenever possible, a meta-analysis was performed on the extracted data, in order to calculate a weighed treatment effect across trials.
    Main results: Eighteen studies met our criteria and were included in the meta-analysis, with a total of 2625 participants. We found evidence of an increase of objective response rates in people treated with chemoimmunotherapy, in comparison with people treated with chemotherapy. Nevertheless, the impact of these increased response rates was not translated into a survival benefit. We found no difference in survival to support the addition of immunotherapy to chemotherapy in the systemic treatment of metastatic melanoma, with a hazard ratio of 0.89 (95% CI 0.72 to 1.11, P = 0.31). Additionally, we found increased hematological and non-hematological toxicities in people treated with chemoimmunotherapy.
    Authors' conclusions: We failed to find any clear evidence that the addition of immunotherapy to chemotherapy increases survival of people with metastatic melanoma. Further use of combined immunotherapy and chemotherapy should only be done in the context of clinical trials.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; Combined Modality Therapy/methods ; Humans ; Immunotherapy/methods ; Interferon-alpha/therapeutic use ; Interleukin-2/therapeutic use ; Melanoma/drug therapy ; Melanoma/secondary ; Melanoma/therapy ; Randomized Controlled Trials as Topic ; Skin Neoplasms/drug therapy ; Skin Neoplasms/therapy
    Chemical Substances Antineoplastic Agents ; Interferon-alpha ; Interleukin-2
    Language English
    Publishing date 2018-02-06
    Publishing country England
    Document type Journal Article ; Meta-Analysis ; Review ; Systematic Review
    ISSN 1469-493X
    ISSN (online) 1469-493X
    DOI 10.1002/14651858.CD005413.pub3
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: A pesquisa

    Clark Otávio Augusto Câmara / Castro Aldemar Araujo

    Pesquisa Odontológica Brasileira, Vol 17, Iss suppl.1, Pp 67-

    2003  Volume 69

    Abstract: O texto traz uma reflexão sobre os principais momentos da execução experimental, e aborda seqüencialmente: a) o que é a pesquisa?, b) por que fazer pesquisa?, c) como a pesquisa pode ser útil posteriormente?, d) quais são as etapas da pesquisa?, e) quem ... ...

    Abstract O texto traz uma reflexão sobre os principais momentos da execução experimental, e aborda seqüencialmente: a) o que é a pesquisa?, b) por que fazer pesquisa?, c) como a pesquisa pode ser útil posteriormente?, d) quais são as etapas da pesquisa?, e) quem serão os autores da pesquisa? Finaliza citando a importância da análise de resultados e sua inserção no contexto da coletividade.
    Keywords Pesquisa ; Ética em pesquisa ; Dentistry ; RK1-715 ; Medicine ; R ; DOAJ:Dentistry ; DOAJ:Health Sciences
    Language English
    Publishing date 2003-01-01T00:00:00Z
    Publisher Universidade de São Paulo
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  3. Article ; Online: A pesquisa Research

    Otávio Augusto Câmara Clark / Aldemar Araujo Castro

    Pesquisa Odontológica Brasileira, Vol 17, Pp 67-

    2003  Volume 69

    Abstract: O texto traz uma reflexão sobre os principais momentos da execução experimental, e aborda seqüencialmente: a) o que é a pesquisa?, b) por que fazer pesquisa?, c) como a pesquisa pode ser útil posteriormente?, d) quais são as etapas da pesquisa?, e) quem ... ...

    Abstract O texto traz uma reflexão sobre os principais momentos da execução experimental, e aborda seqüencialmente: a) o que é a pesquisa?, b) por que fazer pesquisa?, c) como a pesquisa pode ser útil posteriormente?, d) quais são as etapas da pesquisa?, e) quem serão os autores da pesquisa? Finaliza citando a importância da análise de resultados e sua inserção no contexto da coletividade. This text presents a reflection on the chief steps involved in experimental execution, and approaches sequentially the following aspects: a) what is research?, b) why carry out a research?, c) how can a research be useful in the future?, d) what are the stages involved in a research?, and e) who should be considered authors of a research? Finally, this article mentions the importance of results analysis and the relevance of the obtained results to the community.
    Keywords Pesquisa ; Ética em pesquisa ; Research ; Ethics ; Dentistry ; RK1-715 ; Medicine ; R ; DOAJ:Dentistry ; DOAJ:Health Sciences
    Language English
    Publishing date 2003-05-01T00:00:00Z
    Publisher Universidade de São Paulo
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  4. Article ; Online: Antibiotic prophylaxis for transrectal prostate biopsy.

    Zani, Emerson L / Clark, Otavio Augusto Camara / Rodrigues Netto, Nelson

    The Cochrane database of systematic reviews

    2011  , Issue 5, Page(s) CD006576

    Abstract: Background: Transrectal prostate biopsy (TRPB) is a well established procedure used to obtain tissue for the histological diagnosis of carcinoma of the prostate. Despite the fact that TRPB is generally considered a safe procedure, it may be accompanied ... ...

    Abstract Background: Transrectal prostate biopsy (TRPB) is a well established procedure used to obtain tissue for the histological diagnosis of carcinoma of the prostate. Despite the fact that TRPB is generally considered a safe procedure, it may be accompanied by traumatic and infective complications, including asymptomatic bacteriuria (bacteria in the urine), urinary tract infection (UTI), transitory bacteremia (bacteria in the blood), fever episodes, and sepsis (pathogenic microorganisms or their toxins in the blood). Although infective complications after TRPB are well known, there is uncertainty about the necessity and effectiveness of routine prophylactic antibiotics and their adverse effects, as well as a clear lack of standardization.
    Objectives: To evaluate the effectiveness and adverse effects of prophylactic antibiotic treatment in TRPB.
    Search strategy: The search covered the principal electronic databases: MEDLINE, EMBASE, LILACS and the Cochrane Central Register of Controlled Trials (CENTRAL). Experts were consulted and references from the relevant articles were scanned.
    Selection criteria: All randomized, controlled trials (RCTs) of men who underwent TRPB and received prophylactic antibiotics or placebo/no treatment, were selected, and all RCTs looking at one type of antibiotic versus another, including comparable dosages, routes of administration, frequency of administration, and duration of antibiotic treatment.
    Data collection and analysis: Two reviewers (ELZ, OACC) independently selected included trials and extracted study data. Any disagreements were resolved by a third party (NRNJ).
    Main results: Overall, more than 3500 references were considered and 19 original reports with a total of 3599 patients were included.There were 9 trials analysing antibiotics versus placebo/no treatment, with all outcomes significantly favouring antibiotic use (P < 0.05) (I(2) = 0%), including bacteriuria (risk ratio (RR) 0.25 (95% confidence interval (CI) 0.15 to 0.42), bacteremia (RR 0.67, 95% CI 0.49 to 0.92), fever (RR 0.39, 95% CI 0.23 to 0.64), urinary tract infection (RR 0.37, 95% CI 0.22 to 0.62), and hospitalization (RR 0.13, 95% CI 0.03 to 0.55). Several classes of antibiotics were effective prophylactically for TRPB, while the quinolones, with the highest number of studies (5) and patients (1188), were the best analysed. For 'antibiotics versus enema', we analysed four studies with a limited number of patients. The differences between groups for all outcomes were not significant. For 'antibiotic versus antibiotic + enema', only the risk of bacteremia (RR 0.25, 95% CI 0.08 to 0.75) was diminished in the 'antibiotic + enema group'. Seven trials reported the effects of short-course (1 day) versus long-course (3 days) antibiotics. Long course was significantly better than short-course treatment only for bacteriuria (RR 2.09, 95% CI 1.17 to 3.73). For 'single versus multiple dose', there was significantly greater risk of bacteriuria for single-dose treatment (RR 1.98, 95% CI 1.18 to 3.33). Comparing oral versus systemic administration - intramuscular injection (IM), or intravenous (IV) - of antibiotics, there were no significant differences in the groups for bacteriuria, fever, UTI and hospitalization.
    Authors' conclusions: Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.
    MeSH term(s) Antibiotic Prophylaxis/methods ; Bacteremia/prevention & control ; Bacterial Infections/prevention & control ; Bacteriuria/prevention & control ; Biopsy, Needle/adverse effects ; Biopsy, Needle/methods ; Hospitalization/statistics & numerical data ; Humans ; Male ; Prostate/pathology ; Prostatic Neoplasms/pathology ; Urinary Tract Infections/prevention & control
    Language English
    Publishing date 2011-05-11
    Publishing country England
    Document type Journal Article ; Meta-Analysis ; Review ; Systematic Review
    ISSN 1469-493X
    ISSN (online) 1469-493X
    DOI 10.1002/14651858.CD006576.pub2
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article: A pesquisa.

    Clark, Otávio Augusto Câmara / Castro, Aldemar Araujo

    Pesquisa odontologica brasileira = Brazilian oral research

    2003  Volume 17 Suppl 1, Page(s) 67–69

    Abstract: This text presents a reflection on the chief steps involved in experimental execution, and approaches sequentially the following aspects: a) what is research?, b) why carry out a research?, c) how can a research be useful in the future?, d) what are the ... ...

    Title translation Research.
    Abstract This text presents a reflection on the chief steps involved in experimental execution, and approaches sequentially the following aspects: a) what is research?, b) why carry out a research?, c) how can a research be useful in the future?, d) what are the stages involved in a research?, and e) who should be considered authors of a research? Finally, this article mentions the importance of results analysis and the relevance of the obtained results to the community.
    MeSH term(s) Ethics, Research ; Research ; Research Design
    Language Portuguese
    Publishing date 2003-08-14
    Publishing country Brazil
    Document type English Abstract ; Journal Article
    ZDB-ID 2046486-1
    ISSN 1517-7491
    ISSN 1517-7491
    DOI 10.1590/s1517-74912003000500011
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Colony-stimulating factors for chemotherapy-induced febrile neutropenia.

    Mhaskar, Rahul / Clark, Otavio Augusto Camara / Lyman, Gary / Engel Ayer Botrel, Tobias / Morganti Paladini, Luciano / Djulbegovic, Benjamin

    The Cochrane database of systematic reviews

    2014  , Issue 10, Page(s) CD003039

    Abstract: Background: Febrile neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating ...

    Abstract Background: Febrile neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating factors (CSFs), such as granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), are cytokines that stimulate and accelerate the production of one or more cell lines in the bone marrow. Clinical trials have addressed the question of whether the addition of a CSF to antibiotics could improve outcomes in individuals diagnosed with febrile neutropenia. However, the results of these trials are conflicting.
    Objectives: To evaluate the safety and efficacy of adding G-CSF or GM-CSF to standard treatment (antibiotics) when treating chemotherapy-induced febrile neutropenia in individuals diagnosed with cancer.
    Search methods: We conducted the search in March 2014 and covered the major electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and SCI. We contacted experts in hematology and oncology and also scanned the citations from the relevant articles.
    Selection criteria: We searched for randomized controlled trials (RCTs) that compared CSF plus antibiotics versus antibiotics alone for the treatment of chemotherapy-induced febrile neutropenia in adults and children.
    Data collection and analysis: We used the standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis of the selected studies using Review Manager 5 software.
    Main results: Fourteen RCTs (15 comparisons) including a total of 1553 participants addressing the role of CSF plus antibiotics in febrile neutropenia were included. Overall mortality was not improved by the use of CSF plus antibiotics versus antibiotics alone (hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.47 to 1.16) P = 0.19; 13 RCTs; 1335 participants; low quality evidence). A similar finding was seen for infection-related mortality (HR 0.75 (95% CI 0.47 to 1.20) P = 0.23; 10 RCTs; 897 participants; low quality evidence). Individuals who received CSF plus antibiotics were less likely to be hospitalized for more than 10 days (risk ratio (RR) 0.65 (95% CI 0.44 to 0.95) P = 0.03; 8 RCTs; 1221 participants; low quality evidence) and had more number of participants with a more faster neutrophil recovery (RR 0.52 (95% CI 0.34 to 0.81) P = 0.004; 5 RCTs; 794 participants; moderate quality evidence) than those treated with antibiotics alone. Similarly, participants receiving CSF plus antibiotics had shorter duration of neutropenia (standardized mean difference (SMD) -1.70 (95% CI -2.65 to -0.76) P = 0.0004; 9 RCTs; 1135 participants; moderate quality evidence), faster recovery from fever (SMD -0.49 (95% CI -0.90 to -0.09) P value = 0.02; 9 RCTs; 966 participants; moderate quality evidence) and shorter duration of antibiotics use (SMD -1.50 (95% CI -2.83 to -0.18) P = 0.03; 3 RCTs; 457 participants; low quality evidence) compared with participants receiving antibiotics alone. We found no significant difference in the incidence of deep venous thromboembolism (RR 1.68 (95% CI 0.72 to 3.93) P = 0.23; 4 RCTs; 389 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. We found higher incidence of bone or joint pain or flu-like symptoms (RR 1.59 (95% CI 1.04 to 2.42) P = 0.03; 6 RCTs; 622 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. Overall, the methodological quality of studies was moderate to low across different outcomes. The main reasons to downgrade the quality of evidence were inconsistency across the included studies and imprecision of results.
    Authors' conclusions: The use of a CSF plus antibiotics in individuals with chemotherapy-induced febrile neutropenia had no effect on overall mortality, but reduced the amount of time participants spent in hospital and improved their ability to achieve neutrophil recovery. It was not clear whether CSF plus antibiotics had an effect on infection-related mortality. Participants receiving CSFs had shorter duration of neutropenia, faster recovery from fever and shorter duration of antibiotics use.
    MeSH term(s) Adult ; Anti-Bacterial Agents/therapeutic use ; Chemotherapy-Induced Febrile Neutropenia/drug therapy ; Child ; Colony-Stimulating Factors/therapeutic use ; Drug Therapy, Combination ; Fever/chemically induced ; Fever/drug therapy ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use ; Humans ; Neoplasms/drug therapy ; Randomized Controlled Trials as Topic
    Chemical Substances Anti-Bacterial Agents ; Colony-Stimulating Factors ; Granulocyte Colony-Stimulating Factor (143011-72-7) ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
    Language English
    Publishing date 2014-10-30
    Publishing country England
    Document type Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Review ; Systematic Review
    ISSN 1469-493X
    ISSN (online) 1469-493X
    DOI 10.1002/14651858.CD003039.pub2
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: Optimal search strategy for clinical trials in the Latin American and Caribbean Health Science Literature Database (LILACS database)

    Aldemar Araujo Castro / Otávio Augusto Câmara Clark / Álvaro Nagib Atallah

    São Paulo Medical Journal, Vol 117, Iss 3, Pp 138-

    update

    1999  Volume 139

    Keywords Medicine ; R
    Language English
    Publishing date 1999-05-01T00:00:00Z
    Publisher Associação Paulista de Medicina
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  8. Article: Searching the Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS) database improves systematic reviews.

    Clark, Otavio Augusto Camara / Castro, Aldemar Araujo

    International journal of epidemiology

    2002  Volume 31, Issue 1, Page(s) 112–114

    Abstract: Background: An unbiased systematic review (SR) should analyse as many articles as possible in order to provide the best evidence available. However, many SR use only databases with high English-language content as sources for articles. Literatura Latino ...

    Abstract Background: An unbiased systematic review (SR) should analyse as many articles as possible in order to provide the best evidence available. However, many SR use only databases with high English-language content as sources for articles. Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS) indexes 670 journals from the Latin American and Caribbean health literature but is seldom used in these SR. Our objective is to evaluate if LILACS should be used as a routine source of articles for SR.
    Methods: First we identified SR published in 1997 in five medical journals with a high impact factor. Then we searched LILACS for articles that could match the inclusion criteria of these SR. We also checked if the authors had already identified these articles located in LILACS.
    Results: In all, 64 SR were identified. Two had already searched LILACS and were excluded. In 39 of 62 (63%) SR a LILACS search identified articles that matched the inclusion criteria. In 5 (8%) our search was inconclusive and in 18 (29%) no articles were found in LILACS. Therefore, in 71% (44/72) of cases, a LILACS search could have been useful to the authors. This proportion remains the same if we consider only the 37 SR that performed a meta-analysis. In only one case had the article identified in LILACS already been located elsewhere by the authors' strategy.
    Conclusion: LILACS is an under-explored and unique source of articles whose use can improve the quality of systematic reviews. This database should be used as a routine source to identify studies for systematic reviews.
    MeSH term(s) Caribbean Region ; Databases, Bibliographic ; Humans ; Latin America ; Meta-Analysis as Topic ; Review Literature as Topic
    Language English
    Publishing date 2002-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 187909-1
    ISSN 1464-3685 ; 0300-5771
    ISSN (online) 1464-3685
    ISSN 0300-5771
    DOI 10.1093/ije/31.1.112
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article: Amifostine reduces side effects and improves complete response rate during radiotherapy: results of a meta-analysis.

    Sasse, André Deeke / Clark, Luciana Gontijo de Oliveira / Sasse, Emma Chen / Clark, Otávio Augusto Camara

    International journal of radiation oncology, biology, physics

    2006  Volume 64, Issue 3, Page(s) 784–791

    Abstract: Purpose: To evaluate the efficacy of amifostine in diminishing radiotherapy side effects and whether or not it protects the tumor.: Methods and materials: We performed a systematic review and meta-analysis of 14 included randomized controlled trials, ...

    Abstract Purpose: To evaluate the efficacy of amifostine in diminishing radiotherapy side effects and whether or not it protects the tumor.
    Methods and materials: We performed a systematic review and meta-analysis of 14 included randomized controlled trials, comprising 1451 patients, comparing the use of radiotherapy vs. radiotherapy plus amifostine for cancer treatment.
    Results: The use of amifostine significantly reduced the risk of developing mucositis (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.29-0.48; p < 0.00001), esophagitis (OR, 0.38; CI, 0.26-0.54; p < 0.00001), acute xerostomia (OR, 0.24; CI, 0.15-0.36; p < 0.00001), late xerostomia (OR, 0.33; CI, 0.21-0.51; p < 0.00001), dysphagia (OR, 0.26; CI, 0.07-0.92; p = 0.04), acute pneumonitis (OR, 0.15; CI, 0.07-0.31; p < 0.00001) and cystitis (OR, 0.17; CI, 0.09-0.32; p < 0.00001). There was no difference in overall response rate between the groups. However, complete response rate was superior for patients using amifostine (OR, 1.81; CI, 1.10-2.96; p = 0.02).
    Conclusions: This systematic review shows that amifostine significantly reduces the side effects of radiation therapy. The efficacy of radiotherapy was not itself affected by the use of this drug and patients receiving amifostine were able to achieve higher rates of complete response.
    MeSH term(s) Amifostine/therapeutic use ; Cystitis/prevention & control ; Deglutition Disorders/prevention & control ; Esophagitis/prevention & control ; Humans ; Neoplasms/radiotherapy ; Radiation Injuries/prevention & control ; Radiation Pneumonitis/prevention & control ; Radiation-Protective Agents/therapeutic use ; Radiodermatitis/prevention & control ; Randomized Controlled Trials as Topic ; Stomatitis/prevention & control ; Xerostomia/prevention & control
    Chemical Substances Radiation-Protective Agents ; Amifostine (M487QF2F4V)
    Language English
    Publishing date 2006-03-01
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Review
    ZDB-ID 197614-x
    ISSN 1879-355X ; 0360-3016
    ISSN (online) 1879-355X
    ISSN 0360-3016
    DOI 10.1016/j.ijrobp.2005.06.023
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: Bisphosphonates in multiple myeloma: a network meta-analysis.

    Mhaskar, Rahul / Redzepovic, Jasmina / Wheatley, Keith / Clark, Otavio Augusto Camara / Miladinovic, Branko / Glasmacher, Axel / Kumar, Ambuj / Djulbegovic, Benjamin

    The Cochrane database of systematic reviews

    2012  , Issue 5, Page(s) CD003188

    Abstract: Background: Bisphosphonates are specific inhibitors of osteoclastic activity and used in the treatment of patients with multiple myeloma (MM). While bisphosphonates are shown to be effective in reducing vertebral fractures and pain, their role in ... ...

    Abstract Background: Bisphosphonates are specific inhibitors of osteoclastic activity and used in the treatment of patients with multiple myeloma (MM). While bisphosphonates are shown to be effective in reducing vertebral fractures and pain, their role in improving overall survival (OS) remains unclear. This is an update of a Cochrane review first published in 2002 and previously updated in 2010.
    Objectives: To assess the evidence related to benefits and harms associated with use of various types of bisphosphonates (aminobisphosphonates versus nonamino bisphosphonates) in the management of patients with MM. Our primary objective was to determine whether adding bisphosphonates to standard therapy in MM improves OS and progression-free survival (PFS), and decreases skeletal-related morbidity. Our secondary objectives were to determine the effects of bisphosphonates on pain, quality of life, incidence of hypercalcemia, incidence of bisphosphonate-related gastrointestinal toxicities, osteonecrosis of jaw and hypocalcemia.
    Search methods: We searched MEDLINE, LILACS, EMBASE (December 2009 to October 2011) and the Cochrane Controlled Trials Register (all years, latest Issue September 2011) to identify all randomized trials in MM up to October 2011 using a combination of text and MeSH terms. We also handsearched relevant meeting proceedings (December 2009 to October 2011).
    Selection criteria: Any randomized controlled trial (RCT) assessing the role of bisphosphonates and observational studies or case reports examining bisphosphonate-related osteonecrosis of the jaw in patients with MM were eligible for inclusion.
    Data collection and analysis: Two review authors extracted the data. Data were pooled and reported as hazard ratio (HR) or risk ratio (RR) under a random-effects model. Statistical heterogeneity was explored using metaregression.
    Main results: In this update, we included 2 studies (2464 patients) that were not part of our last Cochrane review published in 2010. In this review we included 16 RCTs comparing bisphosphonates with either placebo or no treatment and 4 RCTs with a different bisphosphonate as a comparator. The 20 included RCTs enrolled 6692 patients. Overall methodological quality of reporting was moderate. Thirty per cent (6/20) of trials reported the method of generating the randomization sequence. Forty per cent (8/20) of trials had adequate allocation concealment. Withdrawals and dropouts were described in 60% (12/20) of trials. Pooled results showed no direct effect of bisphosphonates on OS compared with placebo or no treatment (HR 0.96, 95% CI 0.82 to 1.13; P = 0.64). However, there was a statistically significant heterogeneity among the included RCTs (I(2) = 55%, P = 0.01) for OS. To explain this heterogeneity we performed a metaregression assessing the relationship between bisphosphonate potency and improvement in OS, which found indicating an OS benefit with zoledronate (P = 0.058). This provided a further rationale for performing network meta-analyses of the various types of bisphosphonates that were not compared head to head in RCTs. Results from network meta-analyses showed superior OS with zoledronate compared with etidronate (HR 0.43, 95% CI 0.16 to 0.86) and placebo (HR 0.61, 95% CI 0.28 to 0.98). However, there was no difference between zoledronate and other bisphosphonates. Pooled analysis did not demonstrate a beneficial effect of bisphosphonates compared with placebo or no treatment in improving PFS (HR 0.70, 95% CI 0.41 to 1.19; P = 0.18) There was no heterogeneity among trials reporting PFS estimates (I(2) = 35%, P = 0.20).Pooled analysis demonstrated a beneficial effect of bisphosphonates compared with placebo or no treatment on prevention of pathological vertebral fractures (RR 0.74, 95% CI 0.62 to 0.89; I(2) = 7%), skeletal-related events (SRE) (RR 0.80, 95% CI 0.72 to 0.89; I(2) = 2%) and amelioration of pain (RR 0.75, 95% CI 0.60 to 0.95; I(2) = 63%). The network meta-analysis did not show any difference in the incidence of osteonecrosis of the jaw (5 RCTs, 3198 patients) between bisphosphonates. Rates of osteonecrosis of the jaw in observational studies (9 studies, 1400 patients) ranged from 0% to 51%. The pooled results (6 RCTs, 1689 patients) showed no statistically significant increase in frequency of gastrointestinal symptoms with the use of bisphosphonates compared with placebo or no treatment (RR 1.23, 95% CI 0.95 to 1.60; P = 0.11).The pooled results (3 RCTs, 1002 patients) showed no statistically significant increase in frequency of hypocalcemia with the use of bisphosphonates compared with placebo or no treatment (RR 2.19, 95% CI 0.49 to 9.74). The network meta-analysis did not show any differences in the incidence of hypocalcemia, renal dysfunction and gastrointestinal toxicity between the bisphosphonates used.
    Authors' conclusions: Use of bisphosphonates in patients with MM reduces pathological vertebral fractures, SREs and pain. Assuming a baseline risk of 20% to 50% for vertebral fracture without treatment, between 8 and 20 MM patients should be treated to prevent vertebral fracture(s) in one patient. Assuming a baseline risk of 31% to 76% for pain amelioration without treatment, between 5 and 13 MM patients should be treated to reduce pain in one patient. With a baseline risk of 35% to 86% for SREs without treatment, between 6 and 15 MM patients should be treated to prevent SRE(s) in one patient. Overall, there were no significant adverse effects associated with the administration of bisphosphonates identified in the included RCTs. We found no evidence of superiority of any specific aminobisphosphonate (zoledronate, pamidronate or ibandronate) or nonaminobisphosphonate (etidronate or clodronate) for any outcome. However, zoledronate appears to be superior to placebo and etidronate in improving OS.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; Bone Density Conservation Agents/therapeutic use ; Bone Diseases/drug therapy ; Bone Diseases/mortality ; Clodronic Acid/therapeutic use ; Diphosphonates/therapeutic use ; Etidronic Acid/therapeutic use ; Fractures, Bone/prevention & control ; Humans ; Imidazoles/therapeutic use ; Multiple Myeloma/complications ; Multiple Myeloma/drug therapy ; Multiple Myeloma/mortality ; Pamidronate ; Randomized Controlled Trials as Topic ; Zoledronic Acid
    Chemical Substances Antineoplastic Agents ; Bone Density Conservation Agents ; Diphosphonates ; Imidazoles ; Clodronic Acid (0813BZ6866) ; Zoledronic Acid (6XC1PAD3KF) ; Etidronic Acid (M2F465ROXU) ; Pamidronate (OYY3447OMC)
    Language English
    Publishing date 2012-05-16
    Publishing country England
    Document type Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Review ; Systematic Review
    ISSN 1469-493X
    ISSN (online) 1469-493X
    DOI 10.1002/14651858.CD003188.pub3
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top