The next steps in improving the outcomes of advanced ovarian cancer

Worldwide ovarian cancer affects over 200,000 women per year. Overall survival rates are poor due to two predominate reasons. First, the majority of patients present with advanced disease creating significant difficulty with effecting disease eradication. Second, acquisition of chemotherapy resistance results in untreatable progressive disease. Advances in treatment of advanced ovarian cancer involve a spectrum of interventions including improvements in frontline debulking surgery and combination chemotherapy. Anti-angiogenic factors have been shown to have activity in frontline and recurrent disease while novel chemotherapeutic agents and targeted treatments are in development particularly for disease that is resistant to platinum-based chemotherapy. These developments aim to improve the progression-free and overall survival of women with advanced ovarian cancer

Introduction to managing patients with recurrent ovarian cancer

Ovarian cancer is the 5th most common cancer found in women in the UK. It is the leading cause of death from gynaecological cancer, and is the 4th most common cause of cancer death among UK women. Similar to the majority of other cancers, relative survival rates for ovarian cancer are improving, although 5-year mortality rates remain stubbornly low. The stage of the disease at diagnosis is the single most important determinant of ovarian cancer survival, as many patients first present with advanced disease. Treatment of ovarian cancer involves a combination of 'upfront' primary surgery followed by chemotherapy. Platinum/taxane-based chemotherapy is the recommended standard-of-care first-line chemotherapy, but the majority of patients will relapse with drug-resistant disease within 3-5 years. However, not all patients can continue with platinum combination therapies due to loss of activity or toxicity-related issues, including hypersensitivity, neurotoxicity, alopecia and ototoxicity. Therefore the choice of second-line chemotherapy must take into account factors such as platinum-free treatment interval (PFI); patient's performance status; current symptoms; history of and likely future toxicities while on chemotherapy; dosing schedule requirement; and cost of treatment. A consensus in 2010 established 4 distinct subgroups within the ROC patient population based on the PFI: (platinum sensitive <12 months, partially platinum sensitive 6-12 months, platinum resistant <6 months, and refractory disease ≤4 weeks). Within patients with platinum sensitive disease, those with partially platinum sensitive disease remain the most clinically challenging to manage effectively. Non-platinum based combination therapies, in particular trabectedin with pegylated liposomal doxorubicin (PLD), offers new options together with a significant survival advantage relative to PLD alone for these patients

Response to sunitinib (Sutent) in chemotherapy refractory clear cell ovarian cancer

• Case describes a response to sunitinib in clear cell ovarian cancer. • Discussion of unique molecular characteristics of clear cell ovarian cancers; • Practical points regarding dosing and toxicity when using sunitinib discussed

The role of kinin B[indice inférieur 1] receptor in diabetic hyperalgesia

Autoimmune insulin-dependent type 1 diabetes involves an overproduction of cytokines, including interleukin-1[bêta] (IL-1[bêta]) and tumour necrosis factor-[alpha] (TNF-[alpha]), which leads to T-cell-mediated pancreatic [bêta]-cell destruction. It is associated with a series of complications including nephropathy, retinopathy and painful diabetic neuropathy (PDN). Several neurovascular systems are activated in type 1 diabetes including the inducible bradykinin (BK)B[indice inférieur 1] receptor (BKB[indice inférieur 1]-R) subtype which is generally absent or of little impact in healthy states, but highly induced or over-expressed under pathological conditions among which type 1 diabetes, where the over-production of cytokines, the hyperglycemia and the oxidative stress are critical factors for its up-regulation. The present project aimed at studying the development of hyperalgesia in rodent models of type 1 diabetes and characterising the role of the inducible BKB[indice inférieur 1]-R in this diabetic complication, through the use of selective BKB[indice inférieur 1]-R agonists and antagonists. Nociception was evaluated with two types of thermal pain tests; spinal (tail immersion and tail flick tests) and supra-spinal (hot plate and plantar stimulation) tests. Chemically streptozotocin (STZ)-induced diabetic mice and rats showed a marked hyperalgesia that was stable over 4 weeks following the STZ injection. Non-obese diabetic (NOD) and BioBreeding/Worcester (BB/Wor) rats, models of autoimmune spontaneous type 1 diabetes, similarly developed significant hyperalgesia over time (4-32 and 4-24 weeks of age, respectively). Hyperalgesia observed in NOD mice and BB/Wor rats did not correlate with hyperglycemia, but rather preceded the increase in the animal plasma glucose concentration. This finding supports the hypothesis that type 1 diabetic complications start early during the progression of the disease, even before the diagnosis of the state of hyperglycemia. The selective BKB[indice inférieur 1]-R agonist, desArg[indice supérieur 9]BK (DBK), which did not affect nociception in control non-diabetic animals, potentiated hyperalgesia in STZ-diabetic and NOD mice. In addition, the acute and chronic administration of the selective BKB[indice inférieur 1]-R antagonists R-715 and R-954 significantly attenuated diabetic hyperalgesia in all tested animals models. Our results also showed that stimulation of the inducible BKB[indice inférieur 1]-R activates several neurotransmitter systems responsible for the mediation of diabetic hyperalgesia including the substance P (SP), nitric oxide (NO) and calcitonin gene-related peptide (CGRP). Nevertheless, the hyperalgesia observed in wild type diabetic mice was totally absent in the BKB[indice inférieur 1]-R-knockout (KO) diabetic mice in which DBK had no effect on nociceptive responses."--Résumé abrégé par UMI

Continuous 5-fluorouracil in the treatment of breast cancer.

Prolonged infusions of 5-fluorouracil (5-FU) have been used since the early 1960s, but recently there has been a major resurgence of interest, partly because of the advent of electronically controlled portable infusion pumps. This paper looks at the published data on continuously infused 5-FU in breast cancer. As a single agent, bolus 5-FU has a response rate of around 25%; this includes many patients in older series who were chemotherapy naive. The overall response rate across all the studies with continuously infused 5-FU is 29%. However, the majority of these patients were heavily pretreated, and response rates of up to 54% have been reported. What is more encouraging is the response rate in combination chemotherapy--even for pretreated patients with metastatic disease, response rates up to 89% have been found. However, this level of benefit brings a new toxicity--palmar--plantar erythrodysaesthesia; and of course myelotoxicity still remains a problem in the combination regimens. Randomised trials to assess the role of infusional 5-FU are now indicated

Langue et littérature coptes

L'auteur remercie Jean-Luc Fourier pour sa relecture attentive. Le mot « copte », qui vient de l'égyptien ancien, désignait la ville de Memphis, refuge du dieu Ptah. Ce mot s'est transformé en qubti, vocable dont les Arabes allaient désormais désigner les habitants de l'Égypte. Le mot hébreu gibtith figure également dans le Talmud au IIe siècle après J.-C. Le copte constitue la dernière phase de l'évolution de l'ancienne langue égyptienne. Fondée sur le parler du Nouvel Empire, cette langue..