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PARP inhibitors are effective in different types of tumors such as ovarian, breast, prostate and pancreatic cancer. Many studies are in progress and may lead to prescription evolution. PARP inhibitors prescription is almost reserved to patients with a constitutional BRCA mutation or a somatic BRCA alteration or a tumor with a deficiency in homologous recombination. Nowadays, the diagnosis of homologous recombination deficit, HRD, is possible with the prescription of a myChoice CDx (Myriad) test. PARP inhibitors are studied in association with chemotherapy and targeted therapies but also with radiotherapy and with immune checkpoint inhibitors. Access to PARP inhibitors is challenged with the emergence of resistance mechanism. Various trials are now studying the possibility of reversing these resistance mechanisms., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: The potential prognostic value of hypertension and proteinuria of anti-vascular endothelial growth factor (VEGF) drugs has not been assessed in routine clinical practice so far in breast cancer. The objectives of the MARS study were to assess the prevalence of proteinuria and hypertension at baseline, their incidence under anti-VEGF treatment, and to evaluate a possible link with overall survival., Methods: Patients from 8 centres were included between 2009 and 2011 with a follow-up of 1 year. They were naive of any previous anti-VEGF treatment and planned to be started on one. The results of the group of patients with breast cancer receiving bevacizumab are presented., Results: Four hundred and two patients with breast cancer and treated with bevacizumab were included. At inclusion, hypertension prevalence was 12.4%, proteinuria 23.9%. The incidence of de novo proteinuria and hypertension during the follow-up was 61.7% and 16.8%, respectively. Among patients with de novo proteinuria, 62.2% afterwards improved/normalized. No thrombotic microangiopathy was reported. Baseline or de novo proteinuria/hypertension were not associated with overall survival in breast cancer patients treated with bevacizumab., Discussion: These results on the renovascular safety of bevacizumab in breast cancer patients showed that the prevalence of hypertension and proteinuria was high at baseline and, moreover, patients treated with bevacizumab frequently developed de novo hypertension and/or proteinuria. Finally, neither hypertension, nor proteinuria, neither at baseline, nor de novo, were associated with overall survival in our cohort of "real-life'' patients

Despite castrate levels of androgens, the androgen receptor (AR) remains active and continues to drive prostate cancer progression. Since the approval of docetaxel, four additional agents that show a survival benefit have been registered on the basis of randomized phase 3 trials. These have included enzalutamide and abiraterone, two agents designed specifically to affect the androgen axis, sipuleucel-T, which stimulates the immune system and cabazitaxel, a chemotherapeutic agent. Denosumab was shown to significantly delay skeletal-related events. Clinicians are challenged with a multitude of treatment options and potential sequencing of these agents that, consequently, make clinical decision making more complex. The induction of constitutively-active AR splice variants (AR-Vs) driving clonal proliferation of AR-negative and AR-independent metastases may be one major potential mechanism of resistance to new hormone therapies., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Enzalutamide (MDV3100) is a non-steroidal antiandrogen of second generation that has shown efficacy in metastatic castration-resistant prostate cancer (mCRPC). The study AFFIRM demonstrated a statistically significant increase in overall survival among patients who have progressed following a docetaxel chemotherapy. Based on these results, a marketing authorization for enzalutamide has been granted. The enzalutamide has been shown to be generally well tolerated. Other trials are underway to evaluate its earlier use in the management of mCRPC. A pivotal registration phase III study (PREVAIL) is ongoing to investigate the effectiveness of enzalutamide in patients who have not yet received chemotherapy.

Abiraterone acetate and cabazitaxel have shown an overall survival benefit in patients with metastatic castration-resistant prostate cancer following docetaxel failure. Both have been approved in this indication. The search, follow-up and characterisation of circulating tumor cells should help for the response evaluation and the choice between the two treatments. Recently, alpharadin (radium-223 chloride) has demonstrated also an overall survival advantage in a large phase III trial. Other hormone therapies as MDV3100 or TAK700 are very promising. In undifferentiated cancers with neuroendocrine features, etoposide and platinum salts combinations have shown low efficiency.

The Renal Insufficiency and Anticancer Medications (IRMA) study is a French national, observational study, which demonstrated the high prevalence of abnormal renal function in a population of 4,684 solid tumour patients, treated in 15 cancer centers. Among them, 7.2% had a SCR level ≥ 110 mmol/L. In the 1,898 patients with breast cancer, only 31 patients (1.63%) had a SCR level ≥ 110 mmol/L. Nevertheless, respectively 51.8 and 50.8% had a creatinine clearance estimated with the Cockcroft-Gault and aMDRD formulae, below 90 mL/min. Even if the most used medications (anthracyclins, taxanes, trastuzumab, hormone therapies) are not nephrotoxic, these results are important because bevacizumab modifies the need for renal management. In case of renal insufficiency, some other treatments such biphosphonates IV, capecitabin and platin salts need drug dosage adjustment or interruption.

Although the number of men presenting with metastatic prostate cancer has decreased significantly over the last several years, the death rate for those men is essentially unchanged. Effective treatments have not existed for prostate cancer progressing after androgen deprivation therapy until recently. Docetaxel based chemotherapy has demonstrated to extend patient survival in two large randomized studies. These studies have provided the impetus to combine docetaxel with novel biologic drugs to further consolidate the gains in long-term outcome. With the arrival of new therapies such as epothilone analogues, small molecule receptor tyrosine kinase inhibitors, monoclonal antibodies, bone-targeted drugs, antisense oligonucleotides, antiangiogenics drugs and endothelin receptor antagonists, the future of prostate cancer therapy appears promising.

New innovating cancer therapies are becoming available on the market. Because medical innovations put a serious financial burden on healthcare system, it is important to understand their diffusion. To analyze this process of diffusion, the molecule trastuzumab (Herceptin) provided by Roche Laboratories was chosen. Because Herceptin is commercialized since 1999 few data are available for this analysis. The objective of this study is to identify factors and brakes associated with the diffusion of the innovation Herceptin. By identifying these factors and brakes, one can notice that Herceptin is the perfect case to illustrate a successful diffusion. All factors mentioned in E. M. Rogers theory are verified with Herceptin: benefit, simplicity, triability, observability and compatibility. The tolerance is excellent and side effects minimized except for cardiac toxicity for patients previously treated with anthracyclines. The weakness concerning financing has been overcome since France changed the payment system to a prospective payment based on the hospital activity. The only problem left is that the fluorescence in situ hybridisation (FISH) test is still not reimbursed by the social security.

The detection of overexpression of human epidermal growth factor receptor 2 (HER2) in some breast cancer tumors has led to the development of a targeted treatment that is tumor selective, effective at extending life expectancy in the patients with advanced or early breast cancers. Trastuzumab (Herceptin), a humanized monoclonal antibody to HER2 is indicated for patients whose tumor demonstrates an amplified copy number for the HER2 oncogene and/or overexpresses the HER2 oncoprotein. Despite a high level of efficacy in combination with chemotherapy, trastuzumab as single agent has limited effectiveness (up to 30% response rates) and patients who respond to trastuzumab will relapse despite continued treatment. The mechanism of trastuzumab action is not fully understood but has been related to cell cycle inhibition. As to mechanisms of resistance, little is known but many preclinical data raised different hypothesis. Thus, the co-expression of growth factor receptors (EGFR family, IGF-1 R), and the activation of PI3K-Akt pathway, mainly by loss of PTEN function may be responsible for the resistance phenotype. It would be interesting to identify the mechanisms of trastuzumab resistance in breast tumors in order to reverse or prevent it. The characterization of these mechanisms would also provide novel strategies for alternative treatments.

The erbB receptor family is part of the receptor tyrosine kinase superfamily and consists of four members erbB. The erbB receptor family has been shown to play an important role in both the development of the normal breast and the pathogenesis and progression of breast cancer. Receptor overexpression has also been shown to be a negative prognostic indicator and to correlate with both tumor invasiveness and a lack of responsiveness to standard treatment, both chemotherapy and hormonotherapy. The targeting of EGFR mainly resides in two approaches: tyrosine kinase inhibition and monoclonal antibodies blocking ligand fixation. Many experimental data support the potential role of targeting EGFR in breast cancer. Particularly tyrosine kinase inhibitors demonstrates activity as single agent or in association with hormonotherapy, chemotherapy and trastuzumab. The association of Iressa with hormonotherapy points out that theses agents may prevent or differ hormonoresistance. Moreover studies in situ carcinoma suggest that tyrosine kinase inhibitors may play a role in chemoprevention. So, targeting EGFR may be indicated in a large spectrum of breast tumors from early to advanced stages, hormone negative or positive breast tumors. However the complexity of erbB network requires the targeting of multiple molecular sites within the network and the characterization of tumor profiles in order to optimally select patients for these therapies.

One hundred forty-four patients with breast cancer and osteolytic bone metastases were randomized to receive either oral clodronate 1,600 mg/d (73 patients) or placebo (71 patients), in addition to either chemotherapy or hormonal therapy, for up to 12 months. Patients were withdrawn from the study when the 12 months of treatment had been achieve or a new bone event occurred, which was defined as: hypercalcemia (> 3 mmol/l), increase in, or onset of new bone pain due to metastases, requirement of radiotherapy for bone pain relief, pathological fractures (including vertebral collapse, spinal cord compression) or death due to bone metastases. Patients are well balanced according to age, performance status, bone condition, except for fractures, more frequent in the clodronate group (25% vs 12%). Of the 137 evaluable patients, 69 received oral clodronate and 68 placebo. Clodronate significantly delayed the median time to onset of new bone events compared to placebo, respectively 244 days and 180 days (p = 0.05). Hypercalcemia did not occur in the clodronate group but was observed in four placebo-treated patients. Clodronate-treated patients had a significant reduction in pain intensity compared to placebo (p = 0.01; measured using a visual pain scale) and significantly fewer patients receiving clodronate required analgesics (p = 0.02). The evaluation of global efficacy by physicians and patients indicated that clodronate was more efficacious than placebo (respectively p = 0.02 and p = 0.01). No significant difference in incidence of adverse effects was observed between the two groups. Clodronate therapy significantly delayed the occurrence of new bone events in these patients with bone metastases from breast cancer and adds to treatment of malignant osteolysis.

Recently developed drugs are ten to one hundred fold more costly than the chemotherapies of the past while the number of eligible patients and the average duration of treatments are ever increasing. The combined effect of these trends makes budgeting a daunting task, in particular for hospitals with budgetary allocation. Balancing budgets became difficult with the arrival of taxanes, but innovative therapies based on biotechnological advances will further increase the financial slide. Hospital running costs can not be infinitely reduced. Therefore, new rules that govern the financing of innovative therapies become mandatory and budgetary allocations based on DRG evaluations will no longer be feasible.

HER2 is overexpressed in about 25% to 30% of breast cancers and associated with poor prognosis, resistance to hormonotherapy and lack of sensitivity to CMF-based adjuvant chemotherapy. Herceptin (trastuzumab), a humanized monoclonal antibody, administered as a single agent, produces objective responses in phase II trials in patients with metastatic breast cancers overexpressing HER2. It has shown a substantial benefit in a phase III trial which compares a standard first line chemotherapy (doxorubicin and cyclophosphamide or taxol alone) to the same chemotherapy with Herceptin in metastatic breast cancer. The Herceptin arm had significantly higher response rate (+ 53%), an improvement in the median duration of response (+ 57%) as well as in time to progression (+ 65%) compared to chemotherapy alone.

Between 1987 and 1995, 52 breast cancer patients had a surgical resection of lung secondaries. In 40 patients, the diagnosis of metastatic breast cancer could be confirmed following pathological examination. Five-year survival rates of these 40 patients was 54 +/- 8% and 5-year disease free survival was 30 +/- 8%. The median survival (70 months) of these patients was better than that of 57 patients with isolated lung metastases who had been treated conservatively (chemo- or/and hormonotherapy) during the same time interval. Twenty-six patients benefitted from a radical excision and had a longer disease free interval (42 versus 27 months, p = 0.03) than patients who had had a wedge resection. Overall survival was not significantly different (71 versus 41 months, p = 0.07). We feel that isolated lung nodules may best be treated by radical (segment or lobe) excision, in particular since preoperative differential diagnosis with primary lung cancer may be difficult. In the presence of multiple nodules, first line medical treatment by chemo- or hormonotherapy should be advocated, allowing to reduce the tumor load and to optimize survival in association with surgery.

Bladder cancer is a common malignancy and accounts for 8,000 new cases and 4,000 deaths each year in France. Numerous factors may be responsible for the development of this disease, first of which are smoking and occupational exposure to chemicals. Main data regarding etiology, epidemiology and biology of bladder cancer are detailed. Diagnostic and therapeutic advances as well as actual research directions are presented.

Dihydropyrimidine dehydrogenase (DPD) is the principal enzyme involved in the catabolism of 5 fluorouracil (5 FU). The clinical importance of DPD has recently been demonstrated wit the identification of rare cases presenting a severe toxicity to 5 FU related to proven DPD deficiency. We report a new case in a patient with concurrent congenital osteogenesis imperfecta. We were surprised to find another similar association reported by Lyss. It is tempting to speculate that DPD activity may be abnormally regulated in osteogenesis imperfecta patients.

The intravenous administration of Clodronate, a strong inhibitor of osteoclastic activity provides a safe and very effective treatment of hypercalcemia whether secondary to bone metastasis or due to paraneoplastic syndrome. Its action is fast, exclusively osseous and lasts up to 7 days. The response is incomplete when increased renal absorption is the predominant mechanism of hypercalcemia. The data published by Elomaa et al on osteolytic metastases in breast cancer patients show a significant improvement with regard to pain reduction, prevention of fractures as well as hypercalcemia. The results obtained using a 1-yr oral treatment need further confirmation.

Two homosexuals with advanced HIV infection and testicular seminoma stage IIb and IIc were treated with irradiation associated with chemotherapy in one patient. Subdiaphragmatic irradiation was followed by moderate diarrhoea. Initial chemotherapy consisted of cisplatinum, vinblastine, bleomycin replaced by cyclophosphamide after radiotherapy. The use of cyclophosphamide was discontinued after 2 courses due to neutropenia (less than 1500/mm3). Complete tumor remission was achieved in both patients without infection in spite of an aggravation of the CD4 deficit (5/mm3, 52/mm3). The patients died of opportunistic infections 14 and 12 months after terminating treatment. We conclude that cytotoxic and radiation treatment can be administered safely if carefully monitored in these severely immunodepressed patients.

Ninety-four patients with metastatic breast cancer were entered in a prospective randomised trial comparing 2 schedules of the same combination chemotherapy. Group I consisted of 46 patients, treated in a monthly three day course with adriamycin (ADM), cyclophosphamide (CPM), vindesine (VDS) and 5 fluoro-uracil (5 FU). Group II included 48 patients who received the same total monthly doses in 4 injections of ADM, CPM, VDS on days 2, 5, 16, 19 of each month together with a continuous infusion of 5 FU over a total of 10 days (days 1-5 and 15 and 19). Patient characteristics in the 2 groups as regards essential prognostic parameters were identical. We observed no difference in myelosuppression between the 2 groups. There were fewer gastrointestinal side effects in group II. Whereas complete alopecia occurred in 100% of patients in group I, only 33% of patients with the fractionated schedule totally lost their hair. The objective response rates at 8 months were 75 and 74% respectively, but the complete response rates (17.5 versus 28%) showed an advantage for group II. This advantage was not statistically significant. Durations of response were 15 months (group I) and 18 months (group II) and the median survival was 27 months in both. We conclude that prolonged low dose and fractionated administration of chemotherapy over 2 five day courses per month improves the therapeutic index and diminishes side effects.