Sunitinib re-challenge in metastatic renal cell carcinoma treated sequentially with tyrosine kinase inhibitors and everolimus.

Therapy of patients with metastatic renal cell carcinoma (mRCC) requires sequential use of several agents with different mechanisms and minimal cross-resistance between the different agents. Tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors prolong progression-free survival (PFS) in patients with mRCC. Re-challenge with TKIs provides clinical benefit after everolimus in patients with mRCC. We report the case of an mRCC patient with lung and bone metastases, treated sequentially with sunitinib, sorafenib and everolimus. The patient had an objective response in reducing bone metastases, but adaptative and concomitant progression in lung metastases during sunitinib re-challenge. Previously, these lung metastases had responded to sunitinib. This intriguing paradox suggests that not only was sunitinib able to target a specific metastatic site during the re-challenge, as seen by the reduction of bone metastases, but it also elicited a more invasive adaptation and progression of lung tumor cells.

Temsirolimus in metastatic chromophobe renal cell carcinoma after interferon and sorafenib therapy.

Chromophobe renal cell carcinoma (chRCC) is a common subtype of renal cell carcinoma (RCC), occurring in 6-11% of renal carcinoma patients. Limited clinical trial data have shown minimal activity with cytokines and chemotherapy, although small-molecule inhibitors of the vascular endothelial growth factor and platelet-derived growth factor pathways such as sunitinib and sorafenib, which are associated with significant clinical activity in clear-cell RCC (ccRCC), have been associated with a 25% response rate in chRCC. The mammalian target of rapamycin kinase inhibitor temsirolimus demonstrates good clinical activity in ccRCC patients with poor prognosis, with further data suggesting it is an effective treatment for all RCC tumour histologies. This report describes the case of a patient with chRCC who experienced rapid improvement in his general condition and stable disease on treatment with temsirolimus, following disease progression on interferon alfa and sorafenib treatment. This case report suggests that temsirolimus is an effective and appropriate treatment for this RCC tumour subtype.

Efficacy of sunitinib in patients with renal cell carcinoma with bone metastases.

Bone is the second most common metastatic site in patients with renal cell carcinoma presenting with metastases (mRCC) at diagnosis. Complications of metastatic bone disease, including bone pain, fractures, spinal cord compression, and hypercalcaemia, are the primary cause of decline in the quality of life of patients with mRCC. Currently, treatment for mRCC bone metastases is generally palliative. Bisphosphonates are also used; however, the efficacy of bisphosphonates in conjunction with targeted agents is currently unknown. As growth factors play a critical role in the development of bone metastases, there is a biological rationale for the use of targeted agents to treat them. We report here the case of two patients with mRCC with surgically unresectable sacral bone metastases treated with sunitinib, who are still alive with long-term stabilization of metastases of 48 and 31 months. Results suggest targeted agents such as sunitinib may be an effective treatment for bone metastases.

Committee for the protection of persons.

The transposition into French law of Directive 2001/20/CE, which relates to good clinical practice in the conduction of trials on drugs for human use, has required the modification of certain provisions that concern the protection of persons participating in biomedical research, in particular those provisions concerning the conditions for the authorisation of biomedical research. Declaration to the competent authorities now comes prior to authorisation and, henceforth, the prior opinion of a Committee for the Protection of Persons (CPP) must be expressly favourable in order for a trial to be undertaken. Proposals are put forward by this Round Table in order to promote the stability and professionalism of the CPPs.

[Adverse drug reaction reporting in emergency medicine]. / Notification des effets indésirables en médecine d'urgence.

METHODS: A regional survey was performed between June and September 2002, to evaluate knowledge and attitudes of emergency physicians regarding adverse drug reaction (ADR) reporting in a French district. 100 questionnaires completed by physicians working in emergency departments and/or mobile intensive care units were analysed. RESULTS: The frequency of ADRs encountered by emergency practitioners was estimated at > or = 0.73 per year and per physician. The ADR notification rate in emergency medicine was estimated at < or = 6%. A minority of physicians were responsible for the majority of ADR reporting. Sixty-four percent of emergency physicians underestimated the conditions required for ADR notification: 28% thought that certain causality was an absolute necessary condition for notification, while 37% considered that notification was required only for ADRs that were both severe and unexpected. CONCLUSION: Interventions focused on advertising ADR reporting procedures could help to improve the notification rate in emergency medicine.

[EGF receptors in urological cancer. Molecular basis and therapeutic involvements]. / Récepteurs EGF dans les cancers urologiques. Bases moléculaires et iplications thérapeutiques.

Many epithelial cancers have been found to overexpress the receptor to epidermal growth factor (EGFR) including head and neck, breast, colon, lung, prostate, kidney, ovary, brain, pancreas and bladder cancer. Because of the association of EGFR overexpression with overall poor prognosis in patients with cancer, a number of strategies to block or downregulate EGFR have been developed to inhibit tumor proliferation and improve clinical outcome. These include monoclonal antibodies directed against the EGFR such as IMC-C225 which specifically targets EGFR and ZD 1839 (Iressa) capable of inhibiting EGFR tyrosine-kinase in vitro. This report will focus on antibodies that target EGFR in renal cell carcinoma, prostate cancer and bladder cancer.