[Targeted therapy for locally advanced and/or metastatic bladder cancer].

Cancer is a complex disease characterized by a multitude of molecular and genetic abnormalities affecting cell proliferation and differentiation, apoptosis, and mobility (invasion). Each of these alterations represents a potential target for the development of targeted therapy. These new therapies inhibit cell growth and are said to be "cytostatic" in contrast with conventional "cytotoxic" chemotherapy.

Update on the medical treatment of metastatic renal cell carcinoma.

Context: Metastatic renal cell carcinoma (mRCC) has long been treated only by immunotherapy with good results only in a small population of patients. In recent years, major improvements in treatment possibilities have occurred with the advent of anti-angiogenic drugs. In the past 2 yr, pivotal phase III trials have confirmed this major breakthrough by increasing the progression-free survival rates and/or overall survival rates provided by sunitinib, sorafenib, and bevacizumab, and more recently by the mTOR (mammalian target of rapamycin) inhibitors temsirolimus and everolimus.

Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial.

Purpose: Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2.

Patients And Methods: Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy--stratified by Karnofsky performance status and number of metastatic sites--were randomly assigned to lapatinib 1,250 mg daily or HT.

First-line bevacizumab combined with reduced dose interferon-alpha2a is active in patients with metastatic renal cell carcinoma.

Background: In patients with untreated metastatic renal cell carcinoma (mRCC), progression-free survival (PFS) was longer with bevacizumab + interferon (IFN)-alpha than IFN + placebo (AVOREN trial). In this hypothesis-generating study, subgroup analysis was carried out to determine the effect of IFN dose reduction.

Patients And Methods: A total of 649 patients received IFN 9 MIU s.

Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma.

Purpose: Sunitinib and sorafenib are novel tyrosine kinase inhibitors (TKIs) that have shown significant clinical activity in metastatic clear cell renal cell carcinoma (RCC). The activity of sunitinib and sorafenib in non-clear cell histologies has not been evaluated.

Patients And Methods: Clinical features at study entry and treatment outcomes were evaluated in patients with metastatic papillary RCC (PRCC) and chromophobe RCC (ChRCC) who received either sunitinib or sorafenib as their initial TKI treatment in five US and French institutions.

Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial.

Background: Vascular endothelial growth factor (VEGF) inhibition is a valid therapeutic approach in renal cell carcinoma. Therefore, an investigation of the combination treatment of the humanised anti-VEGF monoclonal antibody bevacizumab with interferon alfa was warranted.

Methods: In a multicentre, randomised, double-blind, phase III trial, 649 patients with previously untreated metastatic renal cell carcinoma were randomised to receive interferon alfa-2a (9 MIU subcutaneously three times weekly) and bevacizumab (10 mg/kg every 2 weeks; n=327) or placebo and interferon alfa-2a (n=322).

Medroxyprogesterone, interferon alfa-2a, interleukin 2, or combination of both cytokines in patients with metastatic renal carcinoma of intermediate prognosis: results of a randomized controlled trial.

Background: Few randomized trials have compared the survival benefit of interferon-alfa over controls in metastatic renal cell carcinoma, and none has been performed using interleukin-2. The Programme Etude Rein Cytokines (PERCY) Quattro trial was designed to evaluate both cytokines for their survival benefit to intermediate prognosis patients, who represent the majority of candidates for these treatments.

Methods: Patients were randomized in a 2-by-2 factorial design to medroxyprogesterone acetate 200 mg daily, interferon-alfa 9 million IU 3 times a week, subcutaneous interleukin-2 9 million IU daily, or a combination of both cytokines.

Prognostic factors of metastatic renal cell carcinoma after failure of immunotherapy: new paradigm from a large phase III trial with shark cartilage extract AE 941.

Purpose: We analyzed prognostic factors, described survival and generated a prognostic model in patients with metastatic renal cell carcinoma in whom immunotherapy failed and who were potentially eligible for novel agents.

Materials And Methods: An analysis of the relationship between clinical features and survival was performed in 300 patients with advanced renal cell carcinoma in whom immunotherapy had failed and who were subsequently treated as part of a single, phase III clinical trial with the anti-angiogenic agent Neovastat (shark cartilage extract AE 941). Clinical features were first examined univariately and a stepwise modeling approach based on Cox proportional hazard regression was then performed to generate a multivariate model.

Randomized phase II study of docetaxel plus estramustine and single-agent docetaxel in patients with metastatic hormone-refractory prostate cancer.

Background: Docetaxel (Taxotere)-based regimens are the new standard therapy in advanced hormone-refractory prostate cancer (HRPC). A synergistic activity has been shown with docetaxel in combination with estramustine in vitro; however, the benefit of this combination remains controversial in clinical practice. We assessed the activity and safety of docetaxel alone and docetaxel-estramustine in HRPC.

PET scans for decision-making in metastatic renal cell carcinoma: a single-institution evaluation.

Objective: Therapeutic decision-making in metastatic renal cell carcinoma (MRCC) is based on conventional radiological evaluation. Fluorodeoxyglucose positron emission tomography (FDG-PET) scans may modify this strategy.

Methods: Patients with MRCC for whom a therapeutic decision had been made underwent an FDG-PET scan in order to complete the standard radiological evaluation.

Midterm local efficacy and survival after radiofrequency ablation of lung tumors with minimum follow-up of 1 year: prospective evaluation.

Purpose: To prospectively evaluate the local efficacy of radiofrequency (RF) ablation of lung neoplasms, with a minimum follow-up period of 1 year.

Materials And Methods: Sixty patients (34 men and 26 women; age range, 27-81 years; mean age, 66 years) with 100 lung tumors gave written informed consent to be enrolled in a prospective study that was approved by the local ethics committee. There were five or fewer tumors per patient, each with a diameter of less than 40 mm (mean +/- standard deviation, 17 mm +/- 10).

[New entities in pathological classification and new therapeutic options in renal cell carcinoma].

Therapy for renal cell carcinoma has made considerable progress in the past few years. The aims of this review are to update the pathological classification of this tumor and discuss predictive factors for tumor response and survival in the case of metastasis as well as the place of immunotherapy with interleukine-2 and/or interferon alpha . Furthermore, we will review new therapeutic options and current results on allogeneic stem cell transplantation with non-myeloablative conditioning and HLA genoidentical donors.

Interferon alpha for the treatment of advanced renal cancer.

This paper is an overview on the place of IFN-alpha in metastatic renal cell carcinoma (MRCC). After a presentation of MRCC and the mode of action of IFN-alpha, the results of studies including IFN-alpha alone or in combination with IL-2, chemotherapy and other biological modifiers are presented. Finally, new trends for new drugs, including antiangiogenic therapies, are discussed.

Multicentre EORTC study 16997: feasibility and phase II trial of farnesyl transferase inhibitor & gemcitabine combination in salvage treatment of advanced urothelial tract cancers.

In this study, the feasibility and activity of combined chemotherapy of the farnesyl transferase inhibitor SCH66336 and gemcitabine was evaluated. This therapy was used as second-line treatment in patients with advanced urothelial tract cancer and the influence of SCH66336 exposure on the pharmacokinetics of gemcitabine was also determined. Patients who had received one previous chemotherapy regime for advanced urothelial cancer were treated with a combination of SCH66336 (150 mg in the morning and 100 mg in the evening) and Gemcitabine (1000 mg/m2 on day 1, 8 and 15 per 28-day cycle).

Phase I study and pharmacokinetic of CHS-828, a guanidino-containing compound, administered orally as a single dose every 3 weeks in solid tumours: an ECSG/EORTC study.

CHS 828 is a new guanidino-containing drug. The aim of this study was to determine the maximum tolerated dose (MTD), the recommended dose and the toxicity of CHS 828. CHS 828 was given orally once every 3 weeks.

Prognostic factors of response or failure of treatment in patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Français d'Immunothérapie.

Interleukin-2 (IL2) or/and interferon (IFN) are routinely used for treating patients with metastatic renal cell cancer. However, results are disappointing since most patients experience treatment failure. Within 6 years, the Groupe Français d'Immunothérapie enrolled 782 patients in successive multicenter trials using cytokine regimens.

Interleukin-6, interleukin-10, and vascular endothelial growth factor in metastatic renal cell carcinoma: prognostic value of interleukin-6--from the Groupe Francais d'Immunotherapie.

Purpose: Few clinical prognostic factors have been identified for patients with metastatic renal cell carcinoma (MRCC), and no biomarker is known in this disease. Several endogenous cytokines have demonstrated interesting and significant correlations with survival in these patients. Our objective was to analyze the prognostic value of circulating vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), and interleukin-6 (IL-6).

Baseline mood and psychosocial characteristics of patients developing depressive symptoms during interleukin-2 and/or interferon-alpha cancer therapy.

It has been suggested that patients with subclinical mood symptoms prior to initiating cytokine treatment (as revealed by elevated baseline scores on depression rating scales) are more likely to become clinically depressed during the course of cytokine therapy. The present study was designed to identify which specific preexisting symptoms predict development of depressive symptomatology during treatment with the cytokines, interleukin-2 (IL-2) and/or interferon-alpha (IFN-alpha), in patients with cancer. Thirty-two patients with renal cell carcinoma or malignant melanoma eligible to receive treatment with IL-2 and/or IFN-alpha were enrolled in the study.

[Refining the French system of cost assessment for oncology patients following chemotherapy].

The aim of this study was to check the clinical predictive variables of the variance of the total cost by GHM for patients undergoing chemotherapy. 10 different hospitals registered 537 hospital stays and 1,535 day care sessions. The initial disease, metastases, other pathologies, participation to randomised trial were recorded.

Subcutaneous interleukin-2, interferon alpha-2b and 5-fluorouracil in metastatic renal cell carcinoma as second-line treatment after failure of previous immunotherapy: a phase II trial.

The association of interleukin-2 (IL-2), interferon alpha-2a (IFNalpha), 5-fluorouracil (5-FU) has been reported to induce response in metastatic renal cell carcinoma (MRCC). This study evaluated IL-2, IFNalpha and 5FU as second-line treatment after failure under immunotherapy. A total of 35 patients received IL-2, at 9 x 10(6) IU m(-2), once or t.