Targeted drugs for metastatic renal cell carcinoma

Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
The Lancet (Impact Factor: 45.22). 01/2008; 370(9605):2071-3. DOI: 10.1016/S0140-6736(07)61874-1
Source: PubMed
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Available from: Ethan Basch, May 14, 2014
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    • "For the convenience of hospital staff, most intravenous chemotherapy is being applied during daytime and oral drugs are usually administered once daily, preferentially administered in morning, without putting forward a rationale for this time of dosing.[353637383940] This conventional approach cannot be used for some of the drugs as this lack of attention to the timing of therapy supposes that biological parameters are either constant throughout the 24 hours, or that their variations are unpredictable and/or stochastic. "
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    • "Innovations of science are leading to drastic changes to create new drugs directed at proteins responsible for disease. Molecular-targeted drugs have been developed and are revealing promising results [28]. However, longterm efficacy and adverse events after >5 yr have not been determined yet. "
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    ABSTRACT: Incidence rate of renal cell carcinoma (RCC) differs among countries. The rates of Asian countries are lower than those of countries in North America or Europe but are exceptionally high in Japanese males. Approximately 30% of patients with RCC have metastasis at initial diagnosis, and another 30% have metastasis after nephrectomy. Clinical studies of risk factors in patients with metastatic RCC (mRCC) are mainly based on data from non-Asian patients. We aimed to investigate the prognosis of Japanese patients and their prognostic factors. The subjects of this study were 1463 patients who were clinically diagnosed with RCC with metastasis in 40 Japanese hospitals between January 1988 and November 2002. The primary end point was overall survival calculated from first diagnosis of mRCC to death or last follow-up. We also investigated the relationship between survival and clinical features. The median overall survival time was 21.4 mo. The estimated survival rates at 1, 3, 5, and 10 yr were 64.2%, 35.2%, 22.5%, and 9.1%, respectively; they contrasted with data from the United States of 54%, 19%, 10%, and 6%, respectively for the same periods. A high percentage of patients had undergone nephrectomy (80.5%) and metastasectomy (20.8%), both of which were shown to prolong survival. The median survival time in the present study was approximately twice as long as that of previous studies from North America or Europe. Early diagnosis of metastasis, nephrectomy, metastasectomy, and cytokine-based therapy seemed to improve the prognosis of RCC patients in the present study.
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    • "In a commentary in The Lancet, Motzer and Basch (2007) highlight that important information on the clinical setting , nature of the treatment program, and survival outcomes is necessary to inform the management of patients as well as future trial designs [6]. Other considerations such as cost, patient experience, and adverse events also have an important place in the decision-making process and have complicated the delivery of these new interventional drugs in some settings [11]. "
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    ABSTRACT: Treatment for metastatic renal cell cancer (mRCC) has advanced dramatically with understanding of the pathogenesis of the disease. New treatment options may provide improved progression-free survival (PFS). We aimed to determine the relative effectiveness of new therapies in this field. We conducted comprehensive searches of 11 electronic databases from inception to April 2008. We included randomized trials (RCTs) that evaluated bevacizumab, sorafenib, and sunitinib. Two reviewers independently extracted data, in duplicate. Our primary outcome was investigator-assessed PFS. We performed random-effects meta-analysis with a mixed treatment comparison analysis. We included 3 bevacizumab (2 of bevacizumab plus interferon-a [IFN-a]), 2 sorafenib, 1 sunitinib, and 1 temsirolimus trials (total n = 3,957). All interventions offer advantages for PFS. Using indirect comparisons with interferon-alpha as the common comparator, we found that sunitinib was superior to both sorafenib (HR 0.58, 95% CI, 0.38-0.86, P = < 0.001) and bevacizumab + IFN-a (HR 0.75, 95% CI, 0.60-0.93, P = 0.001). Sorafenib was not statistically different from bevacizumab +IFN-a in this same indirect comparison analysis (HR 0.77, 95% CI, 0.52-1.13, P = 0.23). Using placebo as the similar comparator, we were unable to display a significant difference between sorafenib and bevacizumab alone (HR 0.81, 95% CI, 0.58-1.12, P = 0.23). Temsirolimus provided significant PFS in patients with poor prognosis (HR 0.69, 95% CI, 0.57-0.85). New interventions for mRCC offer a favourable PFS for mRCC compared to interferon-alpha and placebo.
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