[Immunotherapy and tyrosine kinase inhibitors in first-line treatment of metastatic renal cell carcinoma-Which strategy when?].

Immunotherapies with checkpoint inhibitors have led to a paradigm shift in metastatic renal cell carcinoma (mRCC) as they established a new standard in first-line treatment. In addition to the established monotherapy with tyrosine kinase inhibitors, the spectrum of first-line options has now become wider. Based on data from studies and current guideline recommendations, this article discusses possible factors for individual strategies in first-line treatment of mRCC.

[CARD study: relevance for the treatment of advanced prostate cancer].

Background:  Various life-prolonging therapy options are available for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

Objective:  The optimal therapy sequence for mCRPC has been discussed for years. With the final results of the CARD study, important prospective data are available to enlighten the discussion about the therapy sequence.

[Metastatic castration-resistant prostate cancer : Clinical data, new treatment options and therapy monitoring].

Therapies currently available in Germany for metastatic castration-resistant prostate cancer (mCRPC) include docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and radium-223, all of which offer a potential survival benefit that adds up in their sequential application to a significant overall survival benefit. However, the optimal sequencing of these agents is still unclear. In the absence of evidence, treatment selection is based on the particular situation and on comorbid conditions of each individual patient.

The European Medicines Agency approval of axitinib (Inlyta) for the treatment of advanced renal cell carcinoma after failure of prior treatment with sunitinib or a cytokine: summary of the scientific assessment of the committee for medicinal products for human use.

Axitinib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, and VEGFR-3. Based on the positive opinion from the European Medicines Agency (EMA), a marketing authorization valid throughout the European Union (EU) was issued for the treatment of advanced renal cell carcinoma (RCC) after failure of prior treatment with sunitinib or a cytokine. The demonstration of clinical benefit for axitinib was based on a phase III, randomized, open-label, multicenter study of axitinib compared with sorafenib in patients with advanced RCC after failure of a prior systemic first-line regimen containing one or more of the following agents: sunitinib, bevacizumab plus interferon-α, temsirolimus, or cytokines.

Assessing the impact of evolving evidence in renal cell carcinoma treatment: an update of the Renal Cell Carcinoma Appropriateness-based Treatment Toolkit (ReCATT).

The appropriateness of the numerous therapeutic options available for patients with advanced or metastatic renal cell carcinoma (RCC) was evaluated in 2011, using the RAND/University of California, Los Angeles (UCLA) appropriateness methodology to match treatment suitability to a range of patient scenarios. However, the RCC therapeutic area evolves rapidly and a body of new clinical data has accrued in the intervening years; as a result the exercise was repeated in 2013 using the same methodology, expert panel and patient scenarios. The aim of the updated assessment was to update the guidance to clinicians and use it to develop an interactive web-based application, the Renal Cell Carcinoma Appropriateness-based Treatment Toolkit (ReCATT).

[Metastatic castration-resistant prostate cancer: position paper for structured therapy monitoring].

This position paper is intended to help to structure and to standardize therapy monitoring in patients with metastatic castration-resistant prostate cancer (mCRPC). With the treatment options available today, patients with metastatic disease can often maintain good quality of life and stable disease for several years. It is crucial that once a therapy becomes insufficiently effective that it be replaced in a timely manner by a new treatment option.

Treatment algorithm for metastatic renal cell carcinoma--recommendations based on evidence and clinical practice.

Until a few years ago, the treatment options for metastatic renal cell cancer (mRCC) were very limited. The growing understanding of the molecular pathomechanisms underlying RCC allowed the development of new treatment approaches. Meanwhile, several approved target-oriented substances from different drug classes are available for mRCC.

Intermittent versus continuous cyproterone acetate in bone metastatic prostate cancer: results of a randomized trial.

Background: To compare intermittent treatment (IT) versus continuous treatment (CT) using cyproterone acetate (CPA) in bone metastatic prostate cancer patients, we conducted an open-label, multicenter randomized trial. Continuous androgen deprivation therapy is the standard treatment in metastatic prostate cancer. Intermittent treatment might maintain efficacy while toxicity and costs are reduced.

[Metastatic renal cell carcinoma: primary and follow-up treatment].

Systemic treatment of metastatic renal cell carcinoma has changed fundamentally in recent years. So-called targeted therapy gives patients with incurable renal cell cancer the chance of prolonged survival with acceptable quality of life and manageable side effects. Several tyrosine kinase inhibitors and mTOR inhibitors have been evaluated in various clinical settings within prospective trials.

A multinational phase II trial of bevacizumab with low-dose interferon-α2a as first-line treatment of metastatic renal cell carcinoma: BEVLiN.

Background: Avastin and Roferon in Renal Cell Carcinoma (AVOREN) demonstrated efficacy for bevacizumab plus interferon-α2a (IFN; 9 MIU tiw) in first-line metastatic renal cell carcinoma (mRCC). We evaluated bevacizumab with low-dose IFN in mRCC to determine whether clinical benefit could be maintained with reduced toxicity.

Methods: BEVLiN was an open-label, single-arm, multinational, phase II trial.

Evaluation of treatment options for patients with advanced renal cell carcinoma: assessment of appropriateness, using the validated semi-quantitative RAND corporation/University of California, Los Angeles methodology.

A diverse range of treatment options and interventions are available for the management of renal cell carcinoma (RCC), allowing clinicians to tailor therapy to best meet their patient's needs and situation. However, choosing from the plethora of options can be problematic. RCC treatment guidelines advise on the most efficacious agents based upon specific clinical trial populations, but these do not always take into account all the patient factors that influence the suitability of treatment options for individual patients.

Indirect treatment comparison of bevacizumab + interferon-α-2a vs tyrosine kinase inhibitors in first-line metastatic renal cell carcinoma therapy.

Background: The vascular endothelial growth factor inhibitor bevacizumab (BEV) given in combination with interferon-α-2a (IFN), and the tyrosine kinase inhibitors (TKIs) sunitinib (SUN) and pazopanib (PAZ), have all shown significant increase in progression-free survival (PFS) in first-line metastatic renal-cell carcinoma (mRCC) therapy. These targeted therapies are currently competing to be primary choice; hence, in the absence of direct head-to-head comparison, there is a need for valid indirect comparison assessment.

Methods: Standard indirect comparison methods were applied to independent review PFS data of the pivotal Phase III trials, to determine indirect treatment comparison hazard-ratios (HR) with 95% confidence intervals (95% CI).

Costs of managing adverse events in the treatment of first-line metastatic renal cell carcinoma: bevacizumab in combination with interferon-alpha2a compared with sunitinib.

Background: Bevacizumab plus interferon-alpha2a (IFN) prolongs progression-free survival to >10 months, which is comparable with sunitinib as first-line treatment of metastatic renal cell carcinoma (RCC). The two regimens have different tolerability profiles; therefore, costs for managing adverse events may be an important factor in selecting therapy.

Methods: Costs of managing adverse events affecting patients with metastatic RCC eligible for treatment with bevacizumab plus IFN or sunitinib were evaluated using a linear decision analytical model.

Muscle-invasive urothelial carcinoma of the bladder.

Muscle-invasive urothelial (transitional cell) carcinoma is a potentially lethal condition for which an attempt at curative surgery is required. Clinical staging does not allow for accurate determination of eventual pathologic status. Muscle-invasive urothelial carcinoma is a highly progressive disease, and initiation of definitive therapy within 3 months of diagnosis is worthwhile.

Randomized phase II/III trial of interferon Alfa-2a with and without 13-cis-retinoic acid in patients with progressive metastatic renal cell Carcinoma: the European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951).

Purpose: A randomized phase II/III trial was conducted to determine whether combination treatment with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFN-alpha-2a) was superior to IFN-alpha-2a alone in patients with progressive metastatic renal cell carcinoma.

Patients And Methods: Three hundred twenty patients were randomly assigned to treatment with IFN-alpha-2a plus 13-CRA or to IFN-alpha-2a alone. IFN-alpha-2a was given daily subcutaneously, starting at a dose of 3 million units (MU).

Combination of surgery and immunotherapy in metastatic renal cell carcinoma.

The treatment of choice for non-disseminated renal cell cancer (RCC) is surgery. However, the 5-year survival rates for all stages do not exceed 60%, even in contemporary series. Further improvement will most likely have to await the development of a more effective systemic therapy and the application of combined treatment modalities to counter the relatively high number of patients presenting with advanced stages.

The genetic make-up of renal cell tumors.

Recent developments in (molecular genetics have led to a better understanding of renal tumor biology. The current knowledge of the genetics of benign as well as malignant renal tumors is discussed briefly. This knowledge may, in the near future, be used to more accurately diagnose these tumors and also to optimalize individually based therapy.

Interferon-alpha-2a with or without 13-cis retinoic acid in patients with progressive, measurable metastatic renal cell carcinoma.

Background: In patients with metastatic renal cell carcinoma (MRCC), interferon-alpha (IFN) monotherapy leads to response rates of 5-15%, dependent on the selection of patients. In 1995, preclinical and clinical data indicated an improvement of these results if IFN was combined with 13-cis retinoic acid (CRA).

Methods: In a randomized Phase II study, patients with measurable MRCC received either subcutaneous IFN (9 MU daily; Arm A) or the same daily subcutaneous dose of IFN plus oral CRA (1 mg/kg; Arm B).

Identification of multidrug resistance-associated protein 1 and glutathione as multidrug resistance mechanisms in human prostate cancer cells: chemosensitization with leukotriene D4 antagonists and buthionine sulfoximine.

Objective: To assess the involvement of the multidrug resistance-associated protein 1 (MRP1) and the glutathione pathway in the multidrug resistant (MDR) phenotype of prostate cancer in vitro.

Materials And Methods: Chemoselection of human prostate cancer cell lines PC3 and DU145 with etoposide resulted in the resistant cell lines PC3-R and DU-R. Resistance against etoposide, doxorubicin and vincristine, and its reversal with leukotriene D4 antagonists MK-571 and zafirlukast, and buthionine sulfoximine (BSO), was assessed using tetrazolium-dye viability assays.

Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis.

Purpose: Metastatic renal cancer is associated with a poor prognosis. Recent advances in immunotherapy for this problem have rekindled interest in cytoreductive nephrectomy. We report a combined analysis of 2 prospective randomized trials that used an identical study protocol.

Randomized Phase II trial assessing estramustine and vinblastine combination chemotherapy vs estramustine alone in patients with progressive hormone-escaped metastatic prostate cancer.

Based on the results of combined data from three North American Phase II studies, a randomised Phase II study in the same patient population was performed, using combination chemotherapy with estramustine phosphate (EMP) and vinblastine (VBL) in hormone refractory prostate cancer patients. In all, 92 patients were randomised into a Phase II study of oral EMP (10 mg kg day continuously) or oral EMP in combination with intravenous VBL (4 mg m(2) week for 6 weeks, followed by 2 weeks rest). The end points were toxicity and PSA response in both groups, with the option to continue the trial as a Phase III study with time to progression and survival as end points, if sufficient responses were observed.

Recurrence after radical prostatectomy for organ-confined prostate cancer.

Background: Some patients from our radical prostatectomy (RPx) series with organ-confined (pT2) prostate cancer and negative surgical margins show a PSA (prostate specific antigen) relapse. Aim of the study was to analyze this cohort of patients that otherwise would have been considered to be cured.

Patients And Methods: Since the introduction of PSA measurement in the follow-up after RPx, 475 pelvic lymph node dissections with subsequent RPx were performed in our department from 1988 to 1997.

Multidrug resistance in prostate cancer.

Advanced hormone-refractory prostate cancer remains a therapeutic challenge, because all available pharmaceutical concepts have been ineffective in improving cancer-specific survival. Failure of chemotherapy may be caused by multidrug resistance (MDR) mechanisms protecting cancer cells against cytotoxic drugs, and the question arises whether prostate cancer is also using MDR principles resulting in resistance against chemotherapeutic agents. In consequence, an array of diverse pathways known to lead to MDR such as MDR1, MRPs, glutathione, and apoptosis have been examined and partially established at varying degrees in hormone-refractory prostate cancer.