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Background Sorafenib is a potent targeted-therapy that blockades angiogenesis and has demonstrated activity against some sarcoma subtypes. Preclinical studies suggested that treatment with sorafenib plus cytotoxic agents could result in additive efficacy. Methods Patients with advanced soft tissue sarcoma, with or without anthracycline pretreatment were included. Patients received oral sorafenib 400 mg twice daily starting on Day +2, ifosfamide 2.0 g/m2 iv infusion lasting 4 h on days 1, 2 and 3 with concurrent mesna 400 mg/m2 every three weeks until disease progression or unacceptable toxicity or up to a maximum of 6 cycles of ifosfamide (sorafenib could be continued until progressive disease or unacceptable toxicity). Primary objective was progression-free rate (PFR) at 3 and 6 months; secondary objectives were overall response rate (ORR), Progression-free survival (PFS), Overall survival (OS) and safety. This article reports the phase II part of a phase I/II clinical trial. Results Thirty-five patients were enrolled. PFR at 3 and 6 months was 66% (95% CI 48–81) and 37% (95% CI 22–55). Six patients (17%) achieved partial response and 17 (49%) stable disease. Median PFS was 4.8 months (CI 95% 1.94–6.36) and overall survival 16.2 months (95% CI 8.75-NA). Conclusion Treatment with sorafenib plus ifosfamide achieved a significant clinical benefit with an acceptable safety profile in patients with advanced soft tissue sarcoma resistant to anthracyclines, which warrants a more detailed study in randomized clinical trials.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal soft tissue sarcoma of the gastrointestinal tract. Correct diagnosis with thorough use of pathologic and molecular tools of GIST mutations has been of the foremost importance. GIST are usually (95 %) KIT positive and harbor frequent KIT or platelet-derived growth factor receptor α-activating mutations. This deep molecular understanding has allowed the correct classification into risk groups with implications regarding prognosis, essential use in the development of targeted therapies and even response prediction to this drugs. Treatment has been evolving and an update to include lessons learned from recent trials in advanced disease as well as controversies in the adjuvant setting that are changing daily practice, is reviewed here. An effort from the Spanish Group for Sarcoma Research with investigators from the group has been undertaken to launch this third version of the GIST guidelines and provide a practical means for the different disciplines that treat this complex disease.

Clear-cell renal cell carcinoma (RCC) is the most common kidney cancer. New treatment options of localized RCC recently incorporated include laparoscopic surgery, nephron-sparing surgery, ablative techniques and active surveillance. But 50 % of patients may develop disease recurrence attributable to subclinical metastases. In these cases, and considering the low benefits of chemotherapy, new targeted therapies such as tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors have been developed as first- and second-line treatment. Both sunitinib and pazopanib are TKIs that constitute the first-line treatment option in patients with metastatic RCC. As second-line treatment, sequential therapy with a second TKI or a mTOR inhibitor is recommended. This review has collected together a series of recommendations issued by the Spanish Oncology Genitourinary Group with the aim of facilitating the treatment of these patients. Each recommendation is accompanied by the level of evidence and grade of recommendation on the basis of the available data.

The speed at which targeted therapies are being developed and incorporated into the treatment of advanced renal cell carcinoma (RCC) is surprising. After decades in which the only systemic treatment options available for advanced disease were interleukin-2 and interferon-alpha, in the last decade, six new targeted therapies have emerged showing meaningful clinical benefits to patients with advanced RCC through phase III trials. Recently, the Spanish Oncology Genitourinary Group issued its first public statement of recommendations for the optimal management of advanced RCC. However, most pivotal phase III trials on which these recommendations were based have been updated and/or fully reported. Moreover, a new multikinase inhibitor, pazopanib, has emerged with good quality clinical data. In this report, we review in depth the latest phase III data of targeted therapies for advanced RCC and update our recommendations. Furthermore, we hypothesize about the best environment for patients with advanced RCC to receive cancer therapy.

Sunitinib is a multiselective oral inhibitor of several tyrosine-kinase receptors that has demonstrated its efficacy in patients with metastatic and/or unresectable gastrointestinal stroma tumours (GIST) who were resistant to or intolerant to previous treatment with imatinib. The purpose of this study is to assess the cost-effectiveness of sunitinib vs. best supportive care (BSC) in GIST as a second- line treatment, from the perspective of the Spanish National Health System.A Markov model was used to assess the cost effectiveness of sunitinib (50 mg/day, 4 weeks "on" and 2 weeks "off") vs. BSC in GIST as a second-line treatment. Transition probabilities between the three health states considered in the model (progression-free survival (PFS), progression and death) were obtained from a clinical trial [Demetri et al. (2006) Lancet 368:1329-1338]. Health resource data (drugs, medical visits, laboratory and radiology tests, palliative care and adverse events) were obtained from an expert panel. Deterministic and probabilistic sensitivity analyses were conducted.Projected PFS years, life years (LY) and quality of life adjusted years (QALYs) were higher for sunitinib compared with BSC: 0.50 vs. 0.24, 1.59 vs. 0.88 and 1.00 vs. 0.55. Mean costs per patient were 23,259 euros with sunitinib and 1,622 euros with BSC. The incremental cost-effectiveness ratios (ICERs) obtained were: 4,090 euros/month PFS, 30,242 euros/LY and 49,090 euros/QALY gained. The most influential variables for the results were the efficacy and unit cost of sunitinib.According to the efficiency thresholds for oncology patients in developed countries, sunitinib is considered cost-effective vs. BSC with acceptable costs per LY and QALY gained.