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Guidelines on the use of haematopoietic colony-stimulating factors for patients having adjuvant chemotherapy for breast cancer are designed to minimise the risk of neutropaenic infection (Smith TJ, Khatcheressian J, Lyman GH et al. Update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 2006; 3: 187-205; Aapro MS, Bohlius J, Cameron DA et al. Effect of primary prophylactic G-CSF use on systemic therapy administration for elderly breast cancer patients. Breast Cancer Res Treat 2011; 47: 8-32; Carlson RW, Allred DC, Anderson BO et al. Breast cancer. Clinical practice guidelines in oncology. J Natl Compr Canc Netw 2009; 7: 122-192). Non-randomised data suggest that the achievement of planned dose intensity (DI) may have an important effect on survival. This trial compared the effects of granulocyte colony-stimulating factor, GCSF, against standard management following a first neutropaenic event (NE) in achieving planned DI.Adult patients receiving adjuvant or neoadjuvant chemotherapy were randomised following a first NE, defined as hospitalisation due to neutropaenic fever, an absolute neutrophil count (ANC) ≤1.5 × 10(9)/l requiring treatment delay or dose reduction of 15% or more of planned dose. The study was initially planned to enrol 816 patients to detect a difference of 10%. This was difficult to achieve in the timeframe and the trial size was amended. Thus, 407 patients were randomly assigned to filgrastim for 7 days or pegfilgrastim versus standard care. The amended study was designed to have 80% power to detect an absolute difference of 14% of planned DI between the two groups.Most regimens were anthracycline-based many of which included a sequential taxane and/or were in clinical trials. Around 82.7% had an NE in the first three cycles. A total of 401 had calculable relative dose intensity (RDI) data. A target of 85% planned RDI was achieved in only 50% of patients in the control arm compared with 75% in the GCSF arm (P0.0001). A secondary end point revealed a reduction in post-randomisation NEs, 65.7% controls versus 18.2% with GCSF.Secondary intervention with GCSF showed a statistically significant improvement in the achievement of adequate RDI in non-intensive regimens. This may have important clinical implications for outcome.

Resume Objectif Determiner la prevalence de l’incontinence urinaire au sein d’une population de coureuses de loisir interrogees lors d’un marathon. Materiel et methodes Etude observationnelle realisee au cours d’un marathon a partir de l’analyse de questionnaires remis aux participantes avant la course. Le questionnaire a ete remis aux 800 participantes et parmi elles, 517 (64,6 %) ont accepte de le remplir. On distinguait 268 (52,4 %) marathoniennes et 243 (47,5 %) relayeuses. Resultats La moyenne d’âge des coureuses etait de 41,1 (±9,7) ans, 479 (93,7 %) d’entre elles etaient d’origine caucasienne, leur indice de masse corporelle moyen etait de 20,7 (±1,9) kg/m2 et 173 (34 %) etaient nullipares. Parmi les repondeuses, 157 (30,7 %) coureuses ont declare avoir des fuites urinaires (toutes circonstances confondues). Parmi les 157 coureuses qui ont declare une incontinence urinaire, 83 (52,9 %) avaient des fuites lors de la course a pied. Dans la moitie des cas, ces fuites survenaient habituellement en fin d’epreuve. La prevalence de l’incontinence urinaire survenant lors de la toux, l’eternuement ou le rire parmi les repondeuses etait de 96/517 (18,5 %). La prevalence de l’incontinence urinaire sur urgenturies etait de 63/517 (12 %). Concernant la frequence des episodes, 39/517 (7,5 %) femmes declaraient avoir au moins une fuite par semaine. La gene etait evaluee a 1,6 (±1,7), sur une echelle de 0 a 10. Conclusion Dans cette etude, la prevalence de l’incontinence chez des coureuses de loisir etait de 30,7 %, ce qui semble comparable a ce qui est observe en population generale. Niveau de preuve 4.

An RF ion-funnel technique has been developed to extract ions from a high-pressure (10 bar) noble-gas environment into a vacuum (10(-6) mbar). Detailed simulations have been performed and a prototype has been developed for the purpose of extracting Ba-136 ions from Xe gas with high efficiency. With this prototype, ions have been extracted for the first time from high-pressure xenon gas and argon gas. Systematic studies have been carried out and compared to simulations. This demonstration of extraction of ions, with mass comparable to that of the gas generating the high-pressure, has applications to Ba tagging from a Xe-gas time-projection chamber for double-beta decay, as well as to the general problem of recovering trace amounts of an ionized element in a heavy (m > 40 u) carrier gas. (C) 2015 Elsevier B.V. All rights reserved.

Purpose The objectives of the study day were to (i) develop an in-depth understanding around the biology and treatment options; (ii) explore the specific physical and psychosocial needs and consideration including patients perspective; and (iii) gain insight into the development of a dedicated, holistic and multi-disciplinary clinic service and the importance of supporting research, for older women with primary breast cancer. Design The format included presentations (with lectures from external and local faculty, and short research papers from Nottingham) with a number of interactive discussions, and sharing of patients’ experience. Results Four sessions were held covering (i) pathological features, (ii) role of radiotherapy and adjuvant chemotherapy, (iii) role of surgery, geriatric assessment and quality of life issues, and (iv) challenges in running research trials. Conclusions A dedicated and joint team approach is required to improve clinical service and support research, in order to optimise the management of primary breast cancer in older women.

Introduction L’omalizumab (OMZ) est un anticorps anti-IgE indique dans l’urticaire chronique spontanee. Son efficacite est mal connue dans les urticaires inductibles. L’etude XOLUS visait a determiner l’efficacite de l’OMZ dans l’urticaire solaire (US). L’efficacite a court terme a ete precedemment montree et nous presentons ici la duree de maintien de la reponse, ainsi que l’efficacite en cas de reprise du traitement apres arret. Materiel et methodes XOLUS est un essai ouvert de phase II multicentrique, a promotion academique ( NCT02262130 ). Dix patients atteints d’US severe refractaire aux AH1 ont recu 300 mg toutes les 4 semaines d’OMZ a 3 reprises. Les patients ont ete consideres comme repondeurs 4 semaines apres la derniere dose sur l’un des criteres suivants : dose urticarienne minimale (DUM) × 10, DLQI Resultats Quatre semaines apres la premiere serie de traitement, 5 des 10 patients etaient repondeurs, dont 2 qui obtenaient une DUMx10. Huit semaines plus tard (12 semaines apres la derniere injection), les criteres de reponse etaient perdus chez tous, avec notamment retour des DUM aux valeurs pre therapeutiques. Les 5 patients etaient retraites et reevalues a S4bis. Seuls les 2 patients qui avaient, dans la premiere phase de traitement, obtenu une augmentation tres significative de leur DUM repondaient de nouveau, avec disparition des poussees d’US et reaugmentation de la DUM mais avec de nouveau perte de reponse a S12bis. Les 3 autres patients n’obtenaient aucun critere d’efficacite. Discussion Ces resultats montrent, que comme dans l’urticaire chronique spontanee, la reponse therapeutique cesse rapidement apres l’arret du traitement par OMZ dans l’US. Elle n’est regagnee que chez 40 % des patients retraites et uniquement chez ceux qui avaient une augmentation initiale franche de la DUM. Ainsi, seuls 20 % des patients inclus initialement semblent avoir beneficie d’un traitement iteratif par OMZ. Il est a noter que les patients inclus dans l’etude presentaient une US particulierement severe, evoluant depuis de nombreuses annees et ayant resiste a de multiples lignes de traitement. Il serait interessant de tester des modalites therapeutiques par OMZ differentes de celles de l’AMM chez ces patients (posologie adaptee au poids et aux IgE, rapprochement des doses…) et de tester a terme l’anticorps anti-IgE de haute affinite (ligelizumab). Conclusion Le schema therapeutique de l’OMZ dans l’urticaire chronique spontanee ne permet de controler qu’un nombre limite de patients atteints d’US severe et refractaire aux AH1. Des modalites therapeutiques optimales restent a determiner.

Apparent diffusivities of bovine serum albumin (BSA) in bovine erythrocyte suspensions were measured over a range of cell concentrations and shear rates. The work had two purposes: to obtain further validation of a new method for measuring diffusion in suspensions, and to increase understanding of molecular transport in blood. Results were compared to long-standing but poorly validated models of molecular transport in suspensions. All models lacked predictive power; none firmly established the roles of fluid shear and particle volume fraction in determining solute diffusion; and one, the product of a widely quoted review appears to be fundamentally flawed.

Demand is increasing for therapeutic biopharmaceuticals such as monoclonal antibodies. Achieving maximum production of these recombinant proteins under developmental time constraints has been a recent focus of study. The majority of these drugs are currently produced in altered Chinese hamster ovary (CHO) cells due to the high viability and the high densities achieved by these cells in suspension cultures. However, shortening the process of developing and isolating high-producing cell lines remains a challenge. This article focuses on current expression systems used to produce biopharmaceuticals in CHO cells and current methods being investigated to produce biopharmaceuticals more efficiently. The methods discussed include modified gene amplification methods, modifying vectors to improve expression of the therapeutic gene and improving the method of selecting for high-producing cells. Recent developments that use gene targeting as a method for increasing production are discussed.

Los labios menores son dos repliegues cutaneomucosos situados entre los labios mayores. La hipertrofia de los labios menores puede deberse a varios factores, sobre todo congenitos. El objetivo de este articulo es describir las tecnicas de reduccion de la hipertrofia de los labios menores y sus resultados. Hay pocos datos referentes a las indicaciones y las expectativas precisas de las pacientes que solicitan una ninfoplastia de reduccion. Aunque algunas mujeres requieren una reduccion por motivos funcionales (molestias fisicas o sexuales) o por una situacion patologica (espina bifida), la mayoria de las pacientes que solicitan una ninfoplastia de reduccion lo hacen por motivos psicologicos. Las tecnicas consistentes en un colgajo y una reseccion en «V» son las mas descritas. De forma global, estas tecnicas se asocian a buenos resultados anatomicos y funcionales (que van del 89 al 100%). Las complicaciones graves, como las infecciones y las necrosis son muy infrecuentes (

Purpose, patients and methods This retrospective analysis of the BRAVE study evaluated the impact of baseline risk factors and antithrombotic therapy on the risk of thrombovascular events (TVEs) in patients receiving epoetin compared to patients not receiving epoetin. Results Baseline risk factors have a significant impact on TVE risk under epoetin therapy. More than 2 risk factors increased the risk of TVEs in patients receiving epoetin (hazard ratio [HR] 2.89, confidence interval [CI] 1.04–8.02, p value [ p ] = 0.04). In patients on epoetin without antithrombotic therapy, the risk for TVEs was higher (HR 4.11, CI 1.37–12.4, p = 0.01) compared to those who received antithrombotics (HR 1.37, CI 0.59–3.18, p = 0.45). Conclusions Our analysis has identified several risk factors which may impact the risk of TVEs under epoetin therapy. These data suggest that antithrombotic therapy may have the potential to reduce the risk of TVEs under epoetin therapy. These findings are hypothesis-generating and need to be confirmed in a prospective, randomised study.

Anthracyclines are considered to be among the most active agents for the treatment of breast cancer. However, their use is limited by cumulative, dose-related cardiotoxicity. Such cardiotoxicity results in a permanent loss of cardiac myocytes and a progressive reduction in cardiac function following each subsequent dose of anthracycline. Initially, damage to the heart is subclinical; however, increasingly impaired cardiac function can result in cardiovascular symptoms, with serious cardiac injury resulting in chronic heart failure. Since the early detection and treatment of cardiotoxicity can reduce its clinical effects, it is important that oncologists are aware of these adverse effects and manage them appropriately. This review examines the risk factors for anthracycline-associated cardiotoxicity and offers recommendations on strategies to reduce the cardiotoxicity of anthracyclines in the management of patients with advanced breast cancer.

Background: In a phase III trial, 3-weekly capecitabine (1250 mg/m 2 twice daily days 1–14) plus docetaxel (75 mg/m 2 day 1) demonstrated significantly superior overall survival to 3-weekly docetaxel (100 mg/m 2 day 1). We report a retrospective analysis of the impact of capecitabine/docetaxel dose reduction on safety and efficacy. Patients and methods: Safety and efficacy data were analyzed retrospectively according to the actual doses of capecitabine and docetaxel administered. Results: More patients receiving capecitabine/docetaxel (65%) had dose reductions for adverse events than docetaxel alone (35%). In most patients requiring dose reduction with the combination (80%), capecitabine and docetaxel were simultaneously reduced to 950 mg/m 2 and 55 mg/m 2 , respectively. Subsequently, there were fewer cycles (17%) with grade 3/4 adverse events than with the full doses (34%). Time to progression and overall survival appeared to be similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles. Conclusions: Capecitabine/docetaxel dosing flexibility allows management of side-effects without compromising efficacy. This retrospective analysis, as well as multiple phase II studies of taxanes with reduced-dose capecitabine, shows that reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer. In addition, reducing the dose of both agents may be appropriate.

Resume Objectif L'identification du ganglion sentinelle (GS) permettrait dans certains cancers vulvaires d'omettre le curage inguinal et de reduire les sequelles, mais elle ne doit pas faire meconnaitre une atteinte ganglionnaire qui compromettrait le pronostic vital. Patientes et methodes Depuis juin 2002, 38 patientes porteuses de lesions T1 ou T2 ont eu une identification du GS par injection d'isotopes avec scintigraphie, puis detection peroperatoire par sonde de detection isotopique, plus ou moins bleu patente. Cela etait suivi par un curage complet. En cas de lesion de la ligne mediane (26 cas), le curage etait bilateral quels que fussent les resultats de l'identification du GS. Les GS indemnes en histologie standard etaient etudies en immunohistochimie a la recherche de micrometastases. Resultats Un ou plusieurs GS ont ete identifies chez 36 des 38 patientes. Soixante-quatre creux inguinaux ont ete etudies dont 15 etaient metastatiques. Dans neuf de ces 15 creux, le GS etait atteint, dans cinq il n'avait pas ete identifie, dans un il s'agissait d'un faux negatif. Dans ces six derniers creux, le curage contenait des ganglions totalement envahis histologiquement. Dans 19 des 26 tumeurs medianes, l'operateur n'a identifie un GS qu'unilateralement. Le cote sans GS identifie contenait des ganglions metastatiques dans cinq cas. Discussion et conclusion L'echec d'identification du GS peut etre du a un ganglion totalement envahi. Cela doit etre pris en compte en particulier dans la prise en charge des tumeurs medianes ou un drainage qui semble unilateral a la scintigraphie ne doit pas dispenser d'une exploration du cote « muet ».

A microfluidic device for the measurement of solute diffusion as well as particle diffusion and migration in flowing complex fluids is described. The device is particularly suited to obtaining diffusivities in such fluids, which require a desired flow state to be maintained during measurement. A method based on the Loschmidt diffusion theory and short times of exposure is presented to allow calculation of diffusivities from concentration differences in the flow streams leaving the cell.

Summary Exemestane is a potent steroidal aromatase inhibitor (AI) with activity in post-menopausal women with metastatic breast cancer, with a reported clinical benefit (CB) rate of 24.3% after prior AI therapy. Data on 114 patients (112 female, 2 male) were obtained retrospectively at two cancer centres. Sixty-five percent of patients were confirmed as oestrogen receptor (ER) positive. All patients had received prior third-generation AI therapy. Responses were seen in 5% and the overall CB rate (CR+PR+SD⩾24 weeks) was 46%. Median PFS and OS were 18 and 61 weeks, respectively. In patients with visceral disease, the CBR was 33%. Patients with known ER-positive disease had a CBR of 47%, and a median TTP of 19 weeks. No benefit was seen in patients with known ER-negative disease. Survival was better in those with CB (median survival not reached in those with CB, 28 weeks in those without CB P 0.0001 ). Efficacy persisted in those patients who had received ⩾3 prior lines of hormonal therapy, including adjuvant treatment. These data confirm exemestane to be an effective therapy after third-generation non-steroidal AI in post-menopausal ER-positive metastatic breast cancer, including visceral disease.

The incidence of breast cancer increases with age, reaching over 300 per 100 000 in women aged 70–75 years in the UK, increasing to almost 400 per 100 000 in women aged over 85 years. As a healthy 70-year old woman can now expect to live for an average of 15 years, control of breast cancer is likely to significantly affect survival. Variations exist in surgical care, radiotherapy and chemotherapy, depending on age; however, virtually all elderly women with hormone-responsive disease are given adjuvant endocrine therapy, usually tamoxifen. For older women who do not have hormone-responsive cancer, and who have high-risk disease characteristics, questions remain over their best management. Overview data of adjuvant chemotherapy in clinical trials show a significant benefit of chemotherapy for women up to the age of 69 years but, for older women, there are too few data to draw any firm conclusions. When considering treatment options for older women, assessment is critical; functional status and comorbidity are some of the factors linked to shorter survival.

Many patients with breast cancer suffer from anaemia, as a consequence of the disease itself or its treatment. Anaemia has a negative impact on treatment outcome and overall survival, and affects the quality of life (QoL) of patients with cancer. Previously, cancer-related anaemia was treated with blood transfusion, but this is inconvenient, offers only temporary improvement in haemoglobin (Hb) level and is associated with several risks. Consequently, blood transfusion is usually reserved for patients with severe anaemia (Hb levels

Resume Introduction La Societe Francaise de Photodermatologie a realise une etude prospective sur la frequence des photoallergenes rencontres en France et sur la pertinence du choix des differents photoallergenes de 1991 a 2001 afin d’elaborer une batterie standard de photopatchtests. Malades et methodes Treize centres de photobiologie ont participe a l’etude de 1991 a 1995. Dix centres ont participe de 1995 a 2001. Une batterie de photoepidermotests etait posee chez tout malade suspect de photoallergie en 3 exemplaires. A J2 une irradiation en ultraviolet UVA et en spectre total (0,75 DEM) a ete realisee sur les 2 batteries, la 3 e servant de temoin. La lecture etait realisee a J3 et J4. Resultats Deux mille soixante-sept malades ont ete testes. Huit cent cinquante-six, soit 41 p. 100 des malades ont eu un ou plusieurs tests positifs. Il s’agissait dans la majorite des cas de reactions photoallergiques (de 39,7 p. 100 a 60 p. 100 des cas) et d’eczema (29,5 p. 100 a 45.6 p. 100). Les photoaggravations etaient moins frequentes (7,9 p. 100 a 10,3 p. 100). Les cas de phototoxicite etaient rares. Les lactones sesquiterpeniques provoquaient un nombre constant de photoallergie, soit 12 cas en 10 ans. Si les phenothiazines etaient les allergenes les plus photosensibilisants jusqu’en 1995, ils ont ete ensuite devances par le ketoprofene a partir de 1996 avec 107 cas de reactions photosensibilisantes en UVA (75 cas) et en spectre total (32 cas). Venaient ensuite les filtres solaires, les benzophenones (surtout l’Eusolex 4360 avec 54 cas pertinents de photoallergie) et les derives du dibenzoylmethane (avec 31 cas pour l’Eusolex 8020). Les filtres UVB etaient tous potentiellement photosensibilisants mais a un taux faible (allant de 1 a 5 cas). Discussion Nos resultats different de ceux des equipes anglo-saxonnes par la survenue d’un nouveau photoallergene, le ketoprofene qui a provoque un grand nombre de photosensibilisations tant en UVA qu’en UVB. Ceci justifie l’ajout systematique de ce compose dans notre batterie prospective. Les photoallergies ont ete relativement peu frequentes avec au maximum une centaine de cas recenses sur une periode de 10 ans. L’irradiation des photopatchtests en spectre total a permis de mettre en evidence des photosensibilisations non trouvees avec les seuls UVA. Conclusion L’etude des photopatchtests a permis d’uniformiser la methodologie en France, de faire le point sur la frequence des photoallergenes testes et d’elaborer une nouvelle batterie.

Most patients with operable breast cancer now receive postoperative medical treatment in the form of adjuvant chemotherapy, hormone manipulation or both. These additional interventions have led to a significant improvement in disease-free survival and overall survival. Clinical trials suggest that total chemotherapy dose delivered and dose intensity both affect long-term clinical outcomes, yet clinical practice audits conducted in Europe and the USA show that dose reductions and delays are widely applied when haematological toxicities such as neutropenia occur. In order to reduce the risk of neutropenic complications and help deliver chemotherapy planned dose on time, targeted use of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) in breast cancer patients is recommended. The availability of neutropenia risk prediction models and the first once-per-cycle, fixed-dose rHuG-CSF (pegfilgrastim), will allow more patients to benefit from receiving their planned chemotherapy dose on time, and enable the use of new dose-dense chemotherapy strategies in the adjuvant treatment of primary breast cancer. These hold the prospect of further improving chemotherapy treatment outcomes. (C) 2003 Elsevier Ltd. All rights reserved.

Introduction La pemphigoide de la grossesse (PG) est une dermatose bulleuse auto-immune jonctionnelle due a la production d’auto-anticorps (Ac) IgG diriges contre la portion NC16A de la proteine transmembranaire hemidesmosomale BP180. Le diagnostic repose sur la positivite de l’IFD, constamment negative dans l’eruption polymorphe de la grossesse (PUPPP). La distinction de ces deux dermatoses est importante du fait du retentissement fœtal possible de la PG. Afin d’eviter la realisation de biopsie cutanee chez la femme enceinte, nous avons evalue la sensibilite et la specificite de la technique Elisa pour la recherche d’Ac anti-BPAG2 pour differentier la PG de la PUPPP. Materiel et methodes Etude multicentrique retrospective realisee de 2008 a 2014. Les patientes suspectes de PG ou de PUPPP ont ete identifiees a partir du listing des serums analyses dans le Centre de reference des maladies bulleuses auto-immunes. Tous les serums ont ete analyses pour rechercher l’Ac anti BP180-NC16A par la technique Elisa (MBL ou Euroimmun). Le diagnostic de PG etait retenu sur une IFD positive et celui de PUPPP sur la negativite de l’IFD. La sensibilite (Se), specificite (Spe), valeur predictive positive (VPP) et valeur predictive negative (VPN) de l’Elisa BPAG2 ont ete evaluees. Resultats Quatre-vingt un femmes enceintes d’âge moyen 30,8 ans (20,6–45,4) ont ete incluses : 51 PUPPP et 30 PG. La recherche d’Ac antiBPAG2 etait positive chez 29/30 PG (titre moyen a 129 UI [24–200 UI]) et chez 1/51 PUPPP (titre MBL a 24 UI [N Discussion Une premiere etude de Sitaru en 2004 realisee chez 44 PG et 44 donneurs de sang temoins a trouve une sensibilite de 86,3 % et une specificite de 100 % de l’anti-BP180 par la technique Elisa pour le diagnostic de PG. Une deuxieme etude de Powell en 2005 realisee chez 82 PG, 164 PUPPP et 166 sujets sains apparies sur l’âge et le sexe a trouve une sensibilite et une specificite de 96 % de l’anti-BP180 NC16A par la technique Elisa pour le diagnostic de PG. Notre etude confirme l’excellente sensibilite de la detection d’Ac anti-BPAG2 evaluee a 86 % et 96 % dans deux etudes de la litterature, ce d’autant que le seul serum de PUPPP positif pour l’Elisa anti-BPAG2 MBL avait un titre faible et a pu ulterieurement etre controle negatif en Euroimmun. Les VPP et VPN tres elevees retrouvees dans notre etude suggerent que l’Elisa pourrait permettre de remplacer l’IFD pour poser le diagnostic de PG et ainsi limiter la rancon cicatricielle liee a la biopsie. Cet examen a egalement l’avantage d’etre quantitatif et permet d’evaluer l’activite de la maladie, comme dans la pemphigoide bulleuse. Conclusion L’Elisa PB180 est tres sensible et specifique pour le diagnostic de PG ou de PUPPP et devrait en pratique remplacer l’IFD.

Summary The anthracyclines doxorubicin and epirubicin, and the taxanes paclitaxel and docetaxel, are effective chemotherapeutic agents for the first-line and second-line treatment of metastatic breast cancer, and their clinical use is widespread. However, for women whose disease has progressed despite receiving these drugs, treatment options are limited. These women often have a good performance status, and may survive for many months or even years, so they should be given the opportunity to benefit from further chemotherapy. The goals of chemotherapy in these patients are to obtain maximum control of symptoms, prevent serious complications, and increase survival without diminishing quality of life. Several agents are used for this purpose, including fluorouracil, docetaxel (in patients who have already received paclitaxel), vinorelbine, and mitomycin c, but because data from controlled trials are limited, a standard regimen has not yet been established. Moreover, these agents may be inconvenient to administer and can be associated with adverse events requiring hospitalisation. Therefore, there is a clear need for additional therapeutic options for patients with metastatic breast cancer. Ideally, agents should have a convenient method of administration, eg, oral, and should be suitable for home-based rather than hospital-based therapy. Treatment should control disease in at least 20–30% of patients with an acceptable side-effect profile. Novel oral therapies have now been developed and are being used increasingly in patients whose disease has progressed following taxane therapy.

Following the encouraging results achieved with the oral fluoropyrimidine capecitabine in clinical trials, a named patient programme was initiated in the UK, through which patients with advanced breast cancer were prescribed capecitabine monotherapy. In this programme, patients were treated with the standard dose of oral capecitabine (1250 mg/m 2 twice daily on days 1–14 of a 21-day treatment cycle). Efficacy and safety data were collected and analysed from 102 patients receiving outpatient treatment with capecitabine. All patients had previously received chemotherapy and for the majority (75%) this was in the metastatic setting. In total, 482 treatment cycles were administered, with a median of 4.5 treatment cycles (range 1–22) per patient. Tumour responses were observed in 20 patients (20%), with an additional 47 patients (46%) achieving disease stabilisation. The median time to disease progression was 4.1 months and median overall survival was 7.7 months. The most common treatment-related adverse events were palmar-plantar erythrodysaesthesia (PPE) (36%) and gastrointestinal toxicities (diarrhoea (33%) and nausea (24%)). Dose reductions due to adverse events were required in 33% of patients, but capecitabine was administered without a dose reduction for 90% of cycles. The results achieved with capecitabine in this named-patient programme confirm that, under ‘real practice' conditions, capecitabine is active and well tolerated in patients with advanced breast cancer.

A new method which allows precise control of the duration of contact between T cells and antigen-presenting cells (APCs) has been developed. A glass coverslip coated with poly-L-lysine, and then with T cells, was placed at the base of a cylindrical well, and the well was filled with liquid medium. A round coverslip, on which APCs were adhered, was supported on the surface of the medium by surface tension, cell-side down. By withdrawing medium from four capillary holes near the base of the well, the coverslip could be lowered to initiate contact between T cells and APCs at a defined time zero. The contact was broken at desired time points by re-introducing medium into the well in order to separate the two coverslips. Each cell type remained adherent to its original surface after separation for all contact times studied. The T cells were monitored for intracellular calcium mobilization using the fluorescent dye, Fura-2. Contact durations of less than 1 min did not trigger calcium signals. Contact durations of 3 and 5 min induced strong calcium signals. Breaking the contact caused a rapid decrease in intracellular calcium levels. This method of cell manipulation allows precise control of the duration of contact of T cells with APCs, while keeping the cells under continuous observation. The measurements so obtained provide a quantitative understanding of the dynamics of early T cell activation.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 39 - N° 8 - p. 679-681

Between October 1993 and September 1994, 33 women with metastatic breast cancer aged between 29 and 74 years with a median age of 58 were entered into a study of oral chemotherapy from three UK centres. Patients by definition had metastatic disease and were fit and well with performance status 0 or 1 in 23 cases, 2 in seven cases and 3 in two cases (one missing). Five patients had received prior adjuvant CMF chemotherapy, nine first line non-anthracycline containing chemotherapy for relapse, eight patients second line non-anthracycline containing chemotherapy and all patients had had hormone therapy either as adjuvant or for relapsed disease. Adjuvant radiotherapy had been given to 17 and palliative radiotherapy to 12 patients. In nine patients there was one site of disease at start of therapy, in 10 two sites, in 11 three sites and in three patients four or more sites. The regimen comprised oral idarubicin 15 mg/m 2 on day 1, 10 mg/m 2 on days 2 and 3 and oral cyclophosphamide 250 mg/m 2 (maximum 400 mg) on days 1, 2 and 3. Treatment was continued until disease progression or toxicity. Results : Overall 25% of 32 evaluable patients responded objectively including one complete response; 50% of patients had stable disease and 25% of patients progression. Among patients who had had no prior chemotherapy the objective response rate was 37.5%; 45% of patients had symptomatic improvement. The most common severe toxicity was granulocytopenia WHO grade 3 or more in 69.7% of patients. Thrombocytopenia grade 3 or 4 was seen in four patients. Six patients had documented infections and all but four patients had alopecia. All patients complained of mild or moderate fatigue. Nausea and vomiting occurred in 75% of patients but only four individuals had grade 3 toxicity. Two patients stopped therapy after myocardial infarction and one after impaired cardiac function was noted. The median time to progression was 2.7 months (1–11.5 months) and median survival time 8.8 months (1–13+ months). Conclusion : The combination chemotherapy is active in heavily treated patients with manageable toxicity but there are problems in heavily pre-treated patients. There was good compliance in taking medication and at the doses chosen the drugs appear to be suitable for younger fitter patients.

The expression of MIB-1, a marker of proliferation, has been measured in tumours from 61 patients with large (>4 cm) operable breast cancers (T2,3 N0,1M,) treated with primary systemic therapy; either with hormone therapy (27 patients), chemotherapy (17 patients) or hormone therapy followed by chemotherapy (17 patients), in order to determine its role in predicting response and survival. Staining was variable between tumours (1–89% of malignant cells staining). There was no correlation between MIB-1 expression and oestrogen receptor concentration when both parameters were measured as a continuous variable, but MIB-1 values were significantly lower in ER-rich tumours compared with tumours which were ER-poor. Response to hormone treatment was restricted to oestrogen receptor positive tumours. Tumours which responded to treatment also had significantly lower MIB-1 values than those which did not (P< 0.004). In terms of response to chemotherapy, neither ER status or MIB-1 predicted for response. However, MIB-1 values were significantly higher in tumours proceeding to a complete pathological response as compared to those with a lesser degree of response (P< 0.01). The overall survival of patients at 10 years was 50%. Neither ER status or MIB-1 predicted for survival following primary hormone therapy. However, MIB-1 predicted for survival following primary chemotherapy; the survival of patients with tumours which showed high MIB-1 expression was significantly better than the survival of those patients with tumours which showed low MIB-1 expression (P< 0.003). In contrast, in the group of patients treated with chemotherapy after failed hormone therapy, survival was significantly worse in those with high MIB-1 expression (P< 0.005).

Cancer is the second leading cause of death in the world. In the UK cancer has overtaken heart disease as the leading cause of death. Breast cancer is the most common female cancer. In the UK one in 12 women or 27 000 cases of breast cancer present annually. Twothirds of these women are under the age of 70. Most patients have no evidence of metastatic disease at the time of presentation, but many subsequently relapse and the current mortality rate is around 50% [1]. In early disease chemotherapy as adjuvant treatment to surgery gives a 19–30% improvement in relapse-free and a 10–26% improvement in overall survival at 10 years [2]. Although breast cancer is one of the hormone sensitive cancers, one third of women are oestrogen receptor negative at presentation. They tend to be younger and pre-menopausal. All women who have metastatic disease that is initially oestrogen sensitive ultimately develop hormone resistance. Chemotherapy will give response rates of 45–80% with complete response rates of 5–25%. However these responses are short-lived with a median duration of 5–13 months. Subsequent treatments have a poorer result with shorter and fewer complete responses being achieved [3].

Summary Background Given as first- or second-line chemotherapy, docetaxel appears to have great potential in advanced breast cancer. Patients and methods Three hundred and seventy-seven locally advanced or metastatic breast cancer patients received docetaxel (Taxotere®) as part of a named patient programme under the care of 108 oncologists from 61 cancer units across the UK. The recommended starting dose was 100 mg/m2, but patients at higher risk of toxicity started at 75 mg/m2. All patients received corticosteroid premedication. The modal number of prior chemotherapy regimens was 2 (range 1–7), 342 patients (91%) had at least one prior anthracycline-based regimen. Results Response was graded according to the managing clinician's best judgement without formal criteria. The overall response rate (ORR) was 46% among the 331 evaluable patients, 46% among the 299 patients who were ‘anthracycline resistant– and 35% among the 82 patients who were ‘anthracycline refractory’ (progressive disease being the best response obtained to the most recent anthracycline containing regimen). One hundred and ninety-three patients started at the full dose of 100 mg/m2 with an ORR of 55% and 129 started at 75 mg/m2with an ORR of 33%. In October 1997, some two years after the programme had started, 26 of 377 patients were still alive, although no complete remissions have lasted to this date. Kaplan—Meier survival analysis yielded a median survival of 194 days (95% CI: 178–218 days). Haematological parameters were checked before each course of docetaxel and additionally as clinically indicated. The safety data confirmed that docetaxel has a manageable, predictable side effect profile; 29 of 377 (7.7%) patients were hospitalised as a result of neutropenic sepsis. Conclusions The results of this named patient programme over a two year timespan confirm that docetaxel is an effective chemotherapy option in patients with locally advanced and/or metastatic breast cancer, including an ‘anthracycline refractory’ population.

In situ aromatase activity and endogenous levels of oestrone and oestradiol were measure in breast tumours from 11 postmenopausal women with large primary oestrogen receptor positive breast cancers before and after three months systemic therapy with letrozole (2.5 mg daily). Patients were infused before and after treatment with 3 'H androstenedione (20MBq) and 14 C oestrone (1MBq) for 18 hours immediately before surgery. Oestrogens were purified from excised tumours and peripheral plasma. In situ aromatase activity was assessed by determining the relative amounts of 3 H and 14 C in the purified fractions and endogenous oestrone and oestradiol measured by immunoassay. One tumour showed no evidence of in situ oestrogen synthesis both before and after treatment; of the remaining 10 tumours, nine displayed a marked decrease in activity with treatment, the effect being statistically significant ( P = 0.022 by sign test). Endogenous levels of oestrogen (oestradiol + oestrone) also fell with treatment in all 10 tumour pairs examined. These results indicate that systemic therapy with letrozole significantly inhibits in situ oestrogen synthesis and decreases endogenous levels of oestrogen within the breasts of postmenopausal women.

Introduction L’urticaire solaire (US) est une maladie chronique rare, potentiellement handicapante, avec un retentissement important sur la qualite de vie quand les antihistaminiques sont inefficaces. Les options therapeutiques sont alors limitees. L’efficacite des immunoglobulines intraveineuses (IGIV) a ete suggeree dans une etude retrospective sur 7 patients avec une remission chez 5 d’entre eux (71 %). Nous avons voulu confirmer ces resultats en menant une etude prospective. Patients et methodes Une etude multicentrique ouverte de phase II a teste l’efficacite de l’administration d’une cure unique de 2 g/kg de Clairyg ® , administre sur 2 jours, chez les patients atteints d’US severe et refractaire aux antihistaminiques. L’objectif principal etait l’obtention de la remission de l’US aux phototests 12 semaines apres traitement. Les objectifs secondaires etaient : – l’obtention d’une remission clinique ; – une qualite de vie non alteree mesuree par le DLQI ; – une amelioration de 50 % de la severite de la maladie mesuree sur une echelle visuelle analogique, 4 et 12 semaines apres traitement. Cette etude etait financee grâce au programme hospitalier de recherche clinique (PHRC) « Maladies rares », a la Societe francaise de dermatologie et grâce a la mise a disponibilite gracieuse des IGIV par le Laboratoire francais du fractionnement et des biotechnologies (LFB ; Les Ulis, France). Resultats Chez les 9 patients traites par IGIV, la remission de l’US etait observee aux phototests 12 semaines apres traitement chez 2 d’entre eux, avec un taux de reponse de 22 % (IC 95 % 2,8–60,0). Au moins 1 critere de reponse etait observe chez 6 patients (67 %) apres 4 semaines de traitement et chez 5 patients (56 %) apres 12 semaines. Deux patients restaient repondeurs apres 24 semaines, et 1 apres 48 semaines. La tolerance etait dominee par des cephalees moderees a severes survenues chez 56 % des patients. Discussion Si l’objectif principal n’est pas atteint (remission de l’US en conditions experimentales, par phototests), cette etude suggere que la moitie des patients atteints d’US recevant une cure unique de 2 g/kg d’IGIV peut obtenir une reponse clinique apres 12 semaines (remission clinique, qualite de vie non alteree et/ou amelioration de 50 % de la severite initiale de la maladie), tandis que des effets secondaires moderes a severes ne sont pas rares. Conclusion Une cure unique semble insuffisante pour obtenir un controle prolonge de la maladie. Ainsi, l’evaluation future de l’efficacite de cures repetees d’IGIV, avec une surveillance etroite de la balance benefice/risque, reste necessaire.

The aim of this study was to test whether survival for patients with high-grade non-Hodgkin's lymphoma (NHL) can be improved with a non-cross-resistant regimen as compared to a CHOP-based regimen. This is a multicentre study comprising 325 adult patients, median age 58 years, with high-grade non-Hodgkin's lymphoma: patients of any age and performance status were eligible provided they were able to receive the drugs in the regimens. Patients were randomised to either B-CHOP-M (bleomycin, cyclophosphamide, doxorubicin, vincristine, prednisolone and methotrexate) or PEEC-M (methylprednisolone, vindesine, etoposide, chlorambucil and methotrexate) alternating with B-CHOP-M. At a median follow-up of 9 years, there was no significant difference in overall survival or disease-free survival between the two arms. Toxicities for the two regimens were equivalent. This study confirms that for relatively unselected patients with high-grade non-Hodgkin's lymphoma, an alternating multidrug regimen does not improve upon the results obtained with B-CHOP-M.

Breast cancer is the most common female cancer--one woman in 12 will have breast cancer at some stage during her life. Early-stage breast cancer is often curable; however, the prognosis is much worse in patients with multiple lymph node involvement or metastatic disease. The overall survival at five years is approximately 60% in women with positive lymph nodes, decreasing to 27%-44% when more than 10 lymph nodes are involved. After metastatic relapse, the mainstay of treatment is palliative. However, recent advances in supportive care have facilitated investigation into the use of dose-intensive chemotherapy regimens. The advancement of high-dose chemotherapy in breast cancer and results from clinical trials in both metastatic disease and the adjuvant setting are reviewed here. The true benefit of high-dose chemotherapy in breast cancer continues to be investigated. It is hoped that the results of worldwide, randomised clinical trials, due within the next three to five years, will provide a clearer indication of the value of high-dose chemotherapy, its costs and the patients whom it will benefit most.

Recent Phase II studies on the use of myelo-ablative chemotherapy in breast cancer have confirmed that this approach is associated with low mortality and apparent efficacy. In a preceding article the theoretical arguments were presented for testing this approach in the high-risk adjuvant setting; in the current article the clinical data justifying the present approaches for this type of treatment are reviewed. The evidence suggests that peripheral blood stem cell supported myelo-ablative chemotherapy should be tested against conventional regimens in order to determine whether or not the increased expense and toxicity of such an approach is associated with improved survival for women whose axillary node status places them at high risk of disease relapse and subsequent death.

For over a decade pre-operative systemic therapy has been used in early, operable breast cancer. However, we do not yet know its exact role, nor have we yet established the indications for chemotherapy as opposed to endocrine therapy. It offers an opportunity to improve our understanding of the biology of breast cancer, in particular the difference between those tumours that do and those that do respond not to primary therapy. However, there is still much that could be learnt from this approach, and unresolved issues remain, particularly pertaining to the appropriate postoperative treatment strategies for women with tumours that have demonstrated in vivo drug resistance.

BACKGROUND 8-Chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) is undergoing phase I clinical trials as an anticancer drug. However, there is debate as to whether it is a prodrug for its 8-Cl-adenosine metabolite. DESIGN Pharmacokinetics, metabolism and tumour disposition studies have been performed in 7 breast cancer patients receiving continuous infusion (28 day) 8-Cl-cAMP (0.54 or 1.08 mg/kg/day) and tumour biopsies were obtained before and on the last day of infusion. Parallel studies were performed in nude mice bearing the HT29 human colon cancer xenograft after continuous infusion (7 day) of active drug doses (50 or 100 mg/kg/day). RESULTS Steady state plasma levels (Css) of 8-Cl-cAMP in patients ranged from 0.15-0.72 microM but 8-Cl-adenosine was not detected in plasma. In contrast, 8-Cl-cAMP was not detectable in 3 tumour biopsies but 8-Cl-adenosine was present in 2 samples at high concentrations (1.33 and 2.02 microM). In mice, Css of 8-Cl-cAMP ranged from 3.2-4.6 microM and 8-Cl adenosine was present in plasma only at the higher dose (100 mg/kg/day, peak concentration of 2.3 microM). In the HT29 xenograft, 8-Cl-cAMP levels were considerably lower than in plasma (0.37-1.22 microM) while 8-Cl-adenosine was present at 5.3-21.0 microM and 8-Cl-AMP was found at 11.3-35.7 microM. CONCLUSIONS The fate of 8-Cl-cAMP in human tumours is characterised by extensive metabolism to products which are not generally observed in plasma. These data raise the possibility that 8-Cl-cAMP is a prodrug for a product of its metabolism in human tumours.

Introduction L’urticaire solaire (US) est une pathologie chronique rare et invalidante, en particulier quand le traitement de premiere intention par anti-histaminiques (AH1) est inefficace. L’efficacite des anticorps anti-IgE (omalizumab) a ete demontree contre placebo dans l’urticaire spontanee chronique (UCS). Les donnees d’efficacite dans l’US reposent actuellement sur des cas cliniques isoles, avec des resultats discordants. Materiel et methodes Afin d’evaluer l’efficacite et la tolerance de l’omalizumab dans l’US, une etude a promotion academique ouverte multicentrique a ete menee chez des patients atteints d’US severe (DLQI > 10), resistant aux ecrans solaires et aux AH1 qui ont recu une injection sous-cutanee de 300 mg d’omalizumab toutes les 4 semaines (S0, 4 et 8). L’objectif principal etait l’obtention d’une augmentation de plus de 10 fois la dose initiale, de la dose urticarienne minimale (DUM) a S12. Un test statistique binomial a ete utilise (40 % de reponses positives etaient necessaires pour rejeter l’hypothese nulle). Les objectifs secondaires a S12 etaient : DLQI Resultats Dix patients (7 femmes, 3 hommes) d’un âge moyen de 42,9 ans ont ete inclus, avec une US evoluant depuis 7,1 ans en moyenne. Une augmentation d’un facteur 10 de la DUM initiale a S12 etait observee chez 2 patients, soit un taux de reponse de 20 % (95 % IC : 2,52–55,6 ; p = 0,2639). La remission clinique complete (UAS7 = 0) etait observee chez 3 patients (30 %), un DLQI Discussion Un nombre non significatif de patients a atteint l’objectif principal de cette etude. La DUM avait ete choisie comme critere de jugement principal car elle represente l’avantage d’une donnee chiffree objective, reproductible et non influencee par les variations meteorologiques. A contrario, elle ne reflete pas le ressenti du patient et lorsque l’on considere, cette fois, les criteres d’efficacite evalues par le patient, la moitie des malades est repondeuse au traitement, soit un taux proche de celui observe dans les phases III de l’omalizumab dans l’UCS. Conclusion Cette etude de preuve de concept suggere que l’omalizumab pourrait apporter un benefice clinique aux patients atteints d’US chronique severe, refractaire aux anti-histaminiques, avec un profil de tolerance favorable.

Summary This article has dealt significantly with the strengths and deficiencies of the present US system. This is the plan with which we are most familiar. We may be accused of having an axe to grind, but familiarity breeds not contempt, but appreciation of strengths and weaknesses. Those proposals for the future, in the preceding paragraphs, are founded in our analysis of the current system. Further studies will clarify the exact modification required in anaesthesia (and indeed all postgraduate) training. Lacking these, the proposals incorporated herein may provide some direction. Above all, it is critical that, in our haste to improve the system, we do not destroy it.

8-Chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) is progressing through clinical evaluation as an anticancer drug. There is debate as to whether 8-Cl-cAMP is the active principal or its cytotoxic metabolite 8-Cl-adenosine. Separate high-performance liquid chromatographic methods are described for (i) 8-Cl-cAMP and its nucleotide metabolites (with 8-Br-cAMP as internal standard), and (ii) 8-Cl-adenosine. Both methods use a reversed-phase (Spherisorb ODS-2) stationary phase and a mobile phase consisting of sodium phosphate buffer (10 mM, pH 3.5) and methanol but with gradient elution for the nucleotides and isocratic elution for 8-Cl-adenosine. 8-Cl-cAMP and related nucleotides are extracted from plasma using strong anion-exchange solid-phase extraction (SPE) and 8-Cl-adenosine is extracted using reversed-phase (C8) SPE. Both techniques enabled analyses to be performed at high detector sensitivity with minimal interference. Limit of detection in plasma was 10 ng/ml for both 8-Cl-cAMP and 8-Cl-adenosine. When applied to the analysis of plasma samples from a patient treated with a low dose continuous infusion of 25 micrograms/kg/h, steady-state concentrations centred around 60 ng/ml 8-Cl-cAMP were determined. In the same patient 8-Cl-adenosine was not detected. Application of this methodology will aid in the further development of 8-Cl-cAMP as a potential new form of anticancer treatment.

50 postmenopausal women with advanced breast cancer were treated with 4-hydroxy-androstenedione (4-OHA) by intramuscular injection of 500 mg given every 2 weeks for 24 weeks unless progression of disease or intolerable side-effects precluded further treatment. All patients had received prior chemotherapy or hormone therapy and 16 patients had responded to their most recent treatment. 46 patients were evaluable for efficacy; 1 died of progressive disease within 3 weeks and 3 were withdrawn for unrelated medical conditions and were ineligible for assessment. All 50 patients were evaluated for toxicity; systemic symptoms were uncommon but 10 patients reported buttock discomfort. Of the 46 patients assessable for response, 7 (15%) had a partial response and 12 (26%) stable disease with 27 (59%) showing disease progression. The median duration of response was 85 weeks (range 32–219 weeks) and the median time to progression was 12 weeks (range 2–219 weeks).

Th e prognosis for a patient with non-Hodgkin's lymphoma is dependent in a large part on the grade of disease, as well as its stage and the general condition of the patient. It was traditionally thought that patients with low grade lymphoma (LGL) had a generally good prognosis, with many series reporting 5-year survivals in the order of 60%-80%. However, in his Karnofsky Memorial Lecture, Rosenberg highlighted the fact that this population has a continual decline in survival over the subsequent years, so that, by 15 years, they fare worse than patients with high grade disease [1]. Reflecting this recognition that there is a substantial long term mortality from LGL, the treatment polices adopted are wide, from no initial treatment to autologous bone marrow transplant in first remission. There is continuing interest in both the use of newer agents such as purine analogues, as well as radical chemotherapy or radiotherapy. We discuss below some of the treatments that have been and are still being used, and attempt to define patient groups for whom each approach may be justified.

Two Bio-Medicus BP-50 centrifugal pumps and two roller pumps were tested simultaneously with porcine blood at 21° ± 1° C in four in vitro circuits to determine the effect of four combinations of flow and pressure conditions on blood damage. Flows of 300 ml/min (¼-inch inner-diameter tubing in the roller pump) and 1775 ml/min (½-inch inner-diameter tubing in the roller pump) and pressure differences across the pump (∆P = outlet pressure – inlet pressure) of 215 mm Hg (n = 6) and 345 mm Hg (n = 5) were examined. The index of hemolysis (milligrams plasma hemoglobin per 100 L blood pumped) for the BP-50 pump was higher at a flow of 300 ml/min than at a flow of 1775 ml/min (p J Thorac Cardiovasc Surg 1993;106:997-1007)

The design of cardiovascular devices is a complex process that is partially, but never completely, illuminated by scientific information and precise specification of the performance wanted of the device. No design satisfies by only accomplishing its intended goal; it must also avoid unintended, unwanted effects, termed in this chapter failure modes. Discussion of these modes is the principal goal of this chapter, which, however, concludes with a discussion of a feasible process of design that can be carried out in the presence of substantial ignorance. Natural components of the cardiovascular system as models for the exploitation of current technology are suggested to be, at least at present, less useful than are precedent artificial systems.

We report a case of osteonecrosis in a patient treated with adjuvant chemotherapy for breast cancer. A 68-year-old woman presented with severe right hip pain. Seven months after completing a course of 6 cycles of adjuvant Cyclophosphamide, Methotrexate and 5-Fluorouracil with standard anti-emetic prophylaxis of Dexamethasone and Domperidone for a T 2 N 0 M 0 breast cancer. Investigations revealed evidence of osteonecrosis of the right femoral head. Due to ongoing hip pain, she underwent an elective total hip replacement and her mobility has returned almost to normal. Osteonecrosis has been associated with corticosteroids and cytotoxic regimens which omit these agents. Osteonecrosis is a rare complication of cytotoxic therapy but with the increasing use of chemotherapy it should be considered in the differential diagnosis of joint pain in patients who have received anti-tumour therapies.

Summary 80 patients with advanced epithelial ovarian carcinoma were treated for 6 months with cisplatinum and prednimustine following initial surgery. Response to treatment was assessed by second-look surgery. The objective response rate was 69% with 38% achieving a complete response for up to 55 months. The toxicity of this regimen was acceptable. Statistically, de-bulking or partial de-bulking had a significant beneficial effect on the likelihood of a complete response. The best survival figures were associated with maximum de-bulking. The combination of cisplatinum and prednimustine is a new and active regimen for operable advanced epithelial ovarian carcinoma.