Historically, treatment options for soft tissue sarcoma in adults have been limited. Prior to the introduction of trabectedin, only two main cytotoxic drugs were considered active: doxorubicin and ifosfamide (and to a lesser extent dacarbazine). Trabectedin is a unique marine-derived agent with a dual mechanism of action; it shares the mechanisms of action of cytotoxic agents and targeted therapies. The activity of trabectedin in advanced soft tissue sarcoma has been demonstrated in an extensive Phase II clinical trials program in which some interesting new models of use were identified, including maintenance treatment and rechallenge after treatment interruption. After 13 years since trabectedin was first investigated, it continues to be the subject of active research in both academia and industry. Numerous clinical studies currently underway with trabectedin are aiming to resolve a variety of questions in order to optimize its use in clinical practice.

Treatment of advanced soft tissue sarcoma remains a considerable therapeutic challenge. Doxorubicin-based combination therapy produces reasonable objective response rates but this comes at the cost of high associated toxicity in the absence of an overall survival benefit in the first-line setting. When selecting chemotherapeutic options for patients with advanced disease, it is important to define the goals and expectations of treatment. For the majority of patients with refractory soft tissue sarcoma, goals are long-term tumor stabilization with good quality of life. Trabectedin is an excellent choice in these patients. The fifth anniversary of the marketing authorization of Yondelis(®) (PharmaMar S.A., Madrid, Spain; trabectedin) in Europe provides an excellent opportunity to recap current knowledge and see what the future holds with this novel treatment. Trabectedin has made possible new models of care, such as long-term treatment and rechallenge. Its use has also fueled important and necessary debate about the criteria currently used to evaluate tumor response.

Among soft tissue sarcomas, myxoid liposarcomas are exceedingly sensitive to trabectedin. Obvious tumor shrinkage is seen in some patients, whereas nondimensional changes in tumor tissue are seen in others especially after the first cycles of therapy. These patterns of tumor response are reminiscent of the way in which solid tumors respond to targeted therapies. The finding of trabectedin's ability to target the FUS-CHOP-mediated transcriptional block, restoring adipogenic differentiation within the tumor in myxoid liposarcomas, confirmed a 'targeted' activity that differs from its well-known atypical alkylating mechanism of action. Uterine leiomyosarcoma may show similar patterns of dimensional and nondimensional responses to trabectedin. Unusual cases of delayed response are occasionally seen and suggest other mechanisms of action, including activity on the tumor microenvironment which has recently been reported. An intriguing question is whether the different patterns of response have clinically or therapeutically meaningful correlations.

Trabectedin (Yondelis(®) [PharmaMar S.A., Madrid, Spain]) is one of the most promising agents tested in the last two decades in patients with anthracycline/ifosfamide-resistant sarcomas and is the first agent highlighting the notion of prolonged tumor control in advanced soft tissue sarcoma. Indeed, the unusual pattern of tumor response to trabectedin has raised queries about the appropriateness of conventional radiological evaluation of efficacy according to Response Evaluation Criteria in Solid Tumors and has prompted the search for new end points for Phase II studies. The safety profile of trabectedin is unique and much more favorable than that of doxorubicin and ifosfamide especially as regards neutropenia and alopecia. Its efficacy in translocation-related sarcomas suggests a targeted approach to tumor control in these sarcoma subtypes. With numerous Phase II and III studies of trabectedin underway, it appears certain that the current standard-of-care paradigm in advanced soft tissue sarcoma is set for change.

Crizotinib is a first-in-class oral anaplastic lymphoma kinase (ALK) inhibitor targeting ALK-rearranged non-small-cell lung cancer. The therapy was approved by the US FDA in August 2011 and received conditional marketing approval by the European Commission in October 2012 for advanced non-small-cell lung cancer. A break-apart FISH-based assay was jointly approved with crizotinib by the FDA. This assay and an immunohistochemistry assay that uses a D5F3 rabbit monoclonal primary antibody were also approved for marketing in Europe in October 2012. While ALK rearrangement has relatively low prevalence, a clinical benefit is exhibited in more than 85% of patients with median progression-free survival of 8-10 months. In this article, the authors summarize the therapy and alternative test strategies for identifying patients who are likely to respond to therapy, including key issues for effective and efficient testing. The key economic considerations regarding the joint companion diagnostic and therapy are also presented. Given the observed clinical benefit and relatively high cost of crizotinib therapy, companion diagnostics should be evaluated relative to response to therapy versus correlation alone whenever possible, and both high inter-rater reliability and external quality assessment programs are warranted.

Radiotherapy is the main salvage option after primary radical prostatectomy. Radical prostatectomy, cryosurgical ablation and high-intensity focused ultrasound are the main salvage options after primary radiotherapy. After primary radiotherapy, long-term oncological outcome of salvage radical prostatectomy and salvage cryosurgical ablation is fairly comparable with the results of primary radical prostatectomy and primary cryosurgical ablation. Side effects of salvage radical prostatectomy in elite centers are acceptable and side effects of salvage cryosurgical ablation in tertiary centers are almost the same as after primary cryosurgical ablation. Good long-term data after salvage high-intensity focused ultrasound are lacking and the risk of side effects is considerable. After primary radical prostatectomy, there is a high level of evidence for oncological benefit of salvage radiotherapy. Careful patient selection is important for all salvage modalities.

The medical treatment of colorectal cancer (CRC) has evolved greatly in the last 10 years, involving complex combined chemotherapy protocols and, in more recent times, new biologic agents. Advances in adjuvant therapy have been limited to the addition of oxaliplatin and the substitution of oral fluoropyrimidine (e.g., capecitabine) for intravenous 5-fluorouracil with no evidence for improved outcome with biological agents. Clinical benefit from the use of the targeted monoclonal antibodies, bevacizumab, cetuximab and panitumumab, in the treatment of metastatic CRC is now well established, but the optimal timing of their use requires careful consideration to derive the maximal benefit. Evidence to date suggests potentially distinct roles for bevacizumab and EGF receptor-targeted biological agents (cetuximab and panitumumab) in the treatment of metastatic CRC. This article reviews the evidence in support of modern treatments for CRC and the decision-making behind the treatment choices, their benefits and toxicities.