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Goss P.E.,Harvard University | Goss P.E.,Massachusetts General Hospital | Strasser-Weippl K.,Center for Oncology | Lee-Bychkovsky B.L.,Harvard University | And 51 more authors.
The Lancet Oncology | Year: 2014

Cancer is one of the major non-communicable diseases posing a threat to world health. Unfortunately, improvements in socioeconomic conditions are usually associated with increased cancer incidence. In this Commission, we focus on China, India, and Russia, which share rapidly rising cancer incidence and have cancer mortality rates that are nearly twice as high as in the UK or the USA, vast geographies, growing economies, ageing populations, increasingly westernised lifestyles, relatively disenfranchised subpopulations, serious contamination of the environment, and uncontrolled cancer-causing communicable infections. We describe the overall state of health and cancer control in each country and additional specific issues for consideration: for China, access to care, contamination of the environment, and cancer fatalism and traditional medicine for India, affordability of care, provision of adequate health personnel, and sociocultural barriers to cancer control; and for Russia, monitoring of the burden of cancer, societal attitudes towards cancer prevention, effects of inequitable treatment and access to medicine, and a need for improved international engagement. © 2014 Elsevier Ltd.

Tsimafeyeu I.,Kidney Cancer Research Bureau | Bratslavsky G.,New York University
Oncology (Switzerland) | Year: 2015

Dysregulation of fibroblast growth factor (FGF) signaling in renal cell carcinoma is now well understood, and it is becoming increasingly likely that certain tumors become dependent on an activation of this pathway for their growth and survival. Dissecting the FGF/FGF receptor (FGFR) pathway offers the hope of developing new therapeutic approaches that selectively target the FGF/FGFR axis in patients whose tumors are known to harbor FGF/FGFR dysregulation. In this review, we summarize the existing data on the role of FGFR1 in the pathogenesis of renal cell carcinoma and discuss methodological issues for drug investigation in this setting. © 2015 S. Karger AG, Basel.

Tsimafeyeu I.,Kidney Cancer Research Bureau | Zart J.S.,Beijing Hospital | Chung B.,Beijing Hospital
BJU International | Year: 2013

Objectives To evaluate the role of cytoreductive radiofrequency ablation (cRFA) in patients with metastatic renal cell carcinoma (RCC) with small primary tumours treated with immuno- or targeted therapy. To assess the efficacy of sunitinib in patients with metastatic RCC with unresected small primary tumours. Patients and Methods Three parallel single-arm prospective studies were conducted. Eligibility criteria were nearly identical for all trials and included: histopathologically confirmed RCC; metastatic measurable disease; size of primary tumour <5 cm; good or intermediate prognosis according to the Memorial Sloan-Kettering Cancer Center model; and no previous therapy. Study 1: Patients were treated with percutaneous cRFA under computed tomography guidance followed by interferon (IFN)-α, 9 MIU, s.c., three times per week. Study 2: Patients received cRFA followed by sunitinib in repeated 6-week cycles of 50 mg/day orally for 4 weeks, then 2 weeks off treatment. Study 3: Patients with unresected primary RCC received sunitinib alone. The primary endpoint was progression-free survival (PFS). Results Baseline patient characteristics (age, gender, histology, Eastern Cooperative Oncology Group performance status, metastatic sites, primary tumour size) were similar in all three studies. Efficacy data for 114 evaluable patients showed an objective response rate of 8% (95% confidence interval [CI] 4.5, 10.5) for study 1, 28.9% (95% CI 15.2, 34) for study 2, and 31.6% (95% CI 20.3, 38.9) for study 3. The median (95% CI) PFS times were 9.1 (6.9, 10.2), 13.4 (9.8, 14.4) and 12.7 (11.3, 13.5) months for studies 1, 2 and 3, respectively. Objective response rate was significantly higher and PFS significantly longer in the sunitinib trials than in study 1 (P < 0.01 all differences); no differences were found between studies 2 and 3 (objective response rate, P = 0.1; PFS, P = 0.6). Study 1 met its primary endpoint, showing that PFS was significantly longer than the expected 5 months (P = 0.02). The median (95% CI) objective survival (OS) times were greater in study 2 (cRFA/sunitinib) and study 3 (sunitinib-alone) than in study 1 (IFN-α) at 27.2 (22.6, 31.8) and 22.5 (20.7, 24.3) vs 19.5 (16.3, 22.7) months, respectively. Differences were significant (study 1 vs 2, hazard ratio [HR] = 0.55; P = 0.003; study 1 vs study 3 HR = 0.6, P = 0.01). OS was significantly longer in the cRFA/sunitinib group compared with the sunitinib-alone group (HR = 0.71; P = 0.04). There were no unexpected toxicities of medical treatment or complications of cRFA. Conclusions cRFA is a safe and effective approach for select patients with metastatic RCC treated with immunotherapy. The cRFA technique did not improve PFS in patients treated with sunitinib; cRFA probably has impact on OS in these patients. This needs to be tested in a larger trial. Sunitinib was effective in patients with metastatic RCC with unresected small primary tumours. © 2013 BJU International.

Tsimafeyeu I.,Kidney Cancer Research Bureau | Snegovoy A.,Nn Blokhin Russian Cancer Research Center | Varlamov S.,Altai Regional Cancer Center | Safina S.,Tatarstan Regional Cancer Center | And 3 more authors.
Targeted Oncology | Year: 2015

Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR) recommended for patients with metastatic renal cell carcinoma (mRCC) who progressed on previous vascular endothelial growth factor (VEGF) receptor-tyrosine kinase inhibitor therapy. Efficacy of everolimus in patients who progressed on anti-VEGF monoclonal antibody bevacizumab is unknown. We did a multicenter prospective trial of everolimus in patients with mRCC whose disease had progressed on bevacizumab ± interferon alpha (IFN). Patients with clear-cell mRCC which had progressed on bevacizumab ± IFN received everolimus 10 mg once daily. The primary end point was the proportion of patients remaining progression-free for 56 days, and a two-stage Simon design was used, with 80 % power and an alpha risk of 5 %. This study is registered with ClinicalTrials.gov, number NCT02056587. From December 2011 to October 2013, a total of 37 patients (28 M, 9 F) were enrolled. Median age was 60.5 years (range 41–66), 11 % had Eastern Cooperative Oncology Group Performance Status (ECOG PS) >2, and Memorial Sloan-Kettering Cancer Center (MSKCC) favorable/intermediate risk was 38/62 %. Five (14 %) patients had a confirmed partial response and 26 (70 %) patients had a stable disease. Median progression-free survival was 11.5 months (95 % CI, 8.8–14.2). Median overall survival was not reached. No grade 3 or 4 treatment-related toxicities were observed. The most common grade 2 adverse events were fatigue (19 %) and pneumonitis (8 %). Everolimus demonstrated a favorable toxicity profile and promising anti-tumor activity as a second-line therapy in metastatic renal cell carcinoma (RCC) patients previously treated with bevacizumab ± IFN. © 2014, Springer International Publishing Switzerland.

Tsimafeyeu I.,Kidney Cancer Research Bureau | Demidov L.,Nn Blokhin Russian Cancer Research Center
Journal of Cancer Research and Therapeutics | Year: 2010

We report on a family with von Hippel-Lindau (VHL) disease and atypically aggressive renal cell carcinoma. A woman and her brother had progressive VHL disease with multiple tumors in their kidneys. One patient developed pulmonary metastases. The patient who had localized disease received radiofrequency ablation with complete destruction of tumors. Cytoreductive nephrectomy was performed in the case of metastatic disease, following which sunitinib maleate (50 mg orally daily, 4 weeks on, 2 weeks off) was given. Examination after two treatment cycles showed complete regression of all metastases. For 19 months, the patients have been under active observation without disease progression. Also, we detected high immunohistochemical expression of vascular endothelial growth factor receptors 1 and 2 in the cytoplasm and nuclei of tumor cells.

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