Tratamento adjuvante do câncer de colo uterino em estadios iniciais : revisão sistemática quantitativa

Base teórica: Para pacientes com câncer de colo uterino em estádios iniciais (IA2-IIA) e fatores de risco para recorrência, a radioterapia pós-operatória diminui a incidência de recorrência local, embora sem impacto na sobrevida. Os fatores de risco incluem metástases em linfonodos, invasão do espaço linfovascular, invasão com profundidade maior do que 10mm, invasão microscópica de paramétrios, histologia não-escamosa e margens cirúrgicas comprometidas. Além disso, essas pacientes possivelmente estejam sob risco de disseminação subclínica da doença, o que não seria afetado pela radioterapia direcionada à pelve. Desta forma, esta revisão sistemática foi realizada com o objetivo de avaliar as evidências disponíveis para a adição de quimioterapia ao tratamento adjuvante radioterápico de pacientes com câncer de colo uterino em estádios iniciais com fatores de risco de mau prognóstico. Objetivos: Avaliar a sobrevida, a sobrevida livre de progressão e as taxas de recorrência do câncer de colo uterino em estádios iniciais (estádios IA2-IIA) com fatores de risco para recorrência, tratado com quimioterapia e radioterapia adjuvantes versus apenas radioterapia adjuvante. Estratégias de busca: Foram realizadas buscas no Cochrane Gynaecological Cancer Group Trials Register (busca realizada em dezembro de 2004), CENTRAL (a partir de 1993), MEDLINE (a partir de 1966), EMBASE (a partir de 1980), LILACS (a partir de 1982), Biological Abstracts (a partir de 1990), CINHAL (a partir de 1984), SciSearch (a partir de 1991) e Cancerlit (a partir de 1963). Também foram realizadas buscas em resumos de congressos. Critérios de seleção: Foram incluídos todos os ensaios clínicos randomizados controlados comparando quimioterapia e radioterapia adjuvantes (grupo intervenção) com radioterapia adjuvante apenas (grupo controle) no tratamento do câncer de colo uterino em estádio inicial. Extração dos dados e análise: Dois revisores avaliaram de maneira independente os critérios de elegibilidade e de qualidade de cada estudo e extraíram os dados. Resultados: Dois estudos randomizados preencheram os critérios de seleção, incluindo um total de 314 pacientes. As pacientes apresentaram diminuição significativa no risco de morte em 48 meses (hazard ratio 0,43, intervalo de confiança – IC 95% 0,25 – 0,76), o que representou uma redução de 57% no risco de morte e um benefício absoluto de 17%. Em 48 meses, o risco para sobrevida livre de progressão foi estimado em 0,45 (IC 95% 0,28 - 0,74), o que representa uma redução de 55% na razão de chances de progressão da doença e um benefício absoluto de 17%. A recorrência local em 48 meses foi menor no grupo da intervenção (hazard ratio 0,50; IC 95% 0,26 – 0,98). O risco de recorrência à distância não foi diferente entre os dois grupos de tratamento (hazard ratio 0,74; IC 95% 0,36 – 1,52). A recorrência global favoreceu o grupo de intervenção, com razão de chances (RC) de 0,54 (IC 95% 0,33 – 0,90) em 48 meses. A razão de chances para toxicidade grau 3 foi maior no grupo que recebeu quimioterapia (RC 5,19; IC 95% 2,90 – 9,29), da mesma forma que a razão de chances para toxicidade grau 4 (RC 4,62; IC 95% 1,96 - 10,86). Não foram encontrados dados a respeito de qualidade de vida nos estudos avaliados. Conclusão dos revisores: Nesta revisão sistemática, as evidências sugerem haver benefício clínico com a adição de quimioterapia ao tratamento adjuvante radioterápico de pacientes com câncer de colo uterino em estádios iniciais e fatores de risco para recorrência. No entanto, as evidências são limitadas devido ao pequeno número de pacientes incluídas nos estudos e ao curto período de seguimento. Há a necessidade de novos ensaios clínicos randomizados nesta área, com um maior número de pacientes, para que os desfechos possam ser adequadamente avaliados.

Editorial

Readers may have noted that a short but very important announcement was made in the last issue of CLAE, at the top of the contents page. CLAE has been accepted by Thomson Reuters for abstracting and indexing in its SciSearch, Journal Citation Reports, and Current Contents services. This will ensure a greater visibility to the international research community. In addition, in June 2012 CLAE will receive its very first official Impact Factor – a measure of journal influence of importance to authors and readers alike. The impact factor value has not yet been decided but internal estimates by Elsevier estimate it will be around 1, and it will be applied to all CLAE issue back to January 2009 (volume 32). I would guess readers at this stage would have one of two responses – either ‘that's good news’ or perhaps ‘what's an impact factor?’ If you are in the latter camp then allow me to try and explain. Basically the impact factor or citation index of a journal is based on how many times in the previous year papers published in that journal in the previous two years were cited by authors publishing in other journals. So the 2012 impact factor for CLAE is calculated on how many times in 2011 papers that were published in CLAE in 2010 and 2009 were cited in other journals in 2011, divided by the number of papers published in CLAE 2010 and 2009. Essentially authors will try and get their work published in journals with a higher impact factor as it is thought that the paper will be cited more by other authors or the paper will have higher visibility in the arena. For universities having its published output in higher journals is one of the markers used to judge esteem. For individual authors publishing in journals with a higher impact factor or the number of times one of their papers is published is something that they are likely to add to their CVs or demonstrate the importance of their work. Journals with higher impact factors tend to be more review journals or journals with a wider spectrum so for a relatively small journal with a specialised field like CLAE it is great to be listed with a citation index. The awarding of a citation index crowns many changes that CLAE has undergone since the current Editor took the reins in 2005. CLAE has increased from four issues (in 2004) to six issues per year with at least one review article per issue and one article with continuing education per issue. The rejection rate has gone up significantly meaning that only best papers are published (currently it stands at 37%). CLAE has been Medline/Pubmed indexed for a few years now which is also a very important factor in improving visibility of the journal. The submission and reviewing process for CLAE in now entirely online and finally the editorial board has changed from being merely a list of keynote people to being an active group of keynote people who are enthusiastically involved with the journal. From the editorial board one person is appointed as a Reviews Editor plus we have two additional editors who work as Regional Editors. As ever, on behalf of CLAE I would like to thank the BCLA Council for their continued support (especially Vivien Freeman) and Elsevier for their continuing guidance (in particular Andrew Miller and Rosie Davey) and the excellent Editorial Board (Christopher Snyder, Pauline Cho, Eric Papas, Jan Bergmanson, Roger Buckley, Patrick Caroline, Dwight Cavanagh, Robin Chalmers, Michael Doughty, Nathan Efron, Michel Guillon, Nizar Hirji, Meng Lin, Florence Malet, Philip Morgan, Deborah Sweeney, Brian Tighe, Eef van Der Worp, Barry Weissman, Mark Willcox, James Wolffsohn and Craig Woods). And finally, a big thanks to the authors and reviewers who work tirelessly putting manuscripts together for publication in CLAE. Copyright © 2012 Published by Elsevier Ltd.

A systematic review of the cost-effectiveness of targeted therapies for metastatic non-small cell lung cancer (NSCLC)

Background: Non-small cell lung cancer (NSCLC) imposes a substantial burden on patients, health care systems and society due to increasing incidence and poor survival rates. In recent years, advances in the treatment of metastatic NSCLC have resulted from the introduction of targeted therapies. However, the application of these new agents increases treatment costs considerably. The objective of this article is to review the economic evidence of targeted therapies in metastatic NSCLC. Methods: A systematic literature review was conducted to identify cost-effectiveness (CE) as well as cost-utility studies. Medline, Embase, SciSearch, Cochrane, and 9 other databases were searched from 2000 through April 2013 (including update) for full-text publications. The quality of the studies was assessed via the validated Quality of Health Economic Studies (QHES) instrument. Results: Nineteen studies (including update) involving the MoAb bevacizumab and the Tyrosine-kinase inhibitors erlotinib and gefitinib met all inclusion criteria. The majority of studies analyzed the CE of first-line maintenance and second-line treatment with erlotinib. Five studies dealt with bevacizumab in first-line regimes. Gefitinib and pharmacogenomic profiling were each covered by only two studies. Furthermore, the available evidence was of only fair quality. Conclusion: First-line maintenance treatment with erlotinib compared to Best Supportive Care (BSC) can be considered cost-effective. In comparison to docetaxel, erlotinib is likely to be cost-effective in subsequent treatment regimens as well. The insights for bevacizumab are miscellaneous. There are findings that gefitinib is cost-effective in first- and second-line treatment, however, based on only two studies. The role of pharmacogenomic testing needs to be evaluated. Therefore, future research should improve the available evidence and consider pharmacogenomic profiling as specified by the European Medicines Agency. Upcoming agents like crizotinib and afatinib need to be analyzed as well. © Lange et al.