Epidemiology and outcomes of primary sclerosing cholangitis: an Australian multicentre retrospective cohort study.

BACKGROUND AND AIMS: Little is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population. METHODS: We conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers. RESULTS: A total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2-15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival. CONCLUSION: In this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant.

Overview of diagnostics on a small-scale RF source for fusion (ROBIN) and the one planned for the diagnostic beam for ITER.

India is responsible for the supply of diagnostic neutral beam systems for ITER to diagnose its helium ash during the deuterium-tritium plasma phase using the charge exchange recombination spectroscopy technique. Considering the many first of its kind in terms of technologies and beam development aspects, ITER Indian domestic agency has adopted a strategy of developing the technology and beam experimentation in parallel. On the beam development front three test beds, namely, the ROBIN (Rf Operated Beam source in India for Negative ion research), the TWIN (TWo rf driver-based Indigenously built Negative ion source), and the INTF (INdian Test Facility) are presently in their various phases of operation, optimization, and setting up at IPR, respectively. Experiments related to plasma production, beam production, and acceleration up to 30 keV in volume and surface mode have been performed on ROBIN. The maximum negative hydrogen ion current density to a tune of 27 mA/cm2 is obtained in the surface mode with Cs injection. Optimal source performance requires optimal surface conditions, minimum impurities, careful characterization of the plasma, cesium feed and its redistribution, and optimal wall temperatures of the surfaces of the plasma box and the plasma grid. A combination of probe, optical, vacuum, laser based, electrical, and calorimetric diagnostic measurements enables such a control. At ROBIN, the above diagnostics are being used regularly. The operational and diagnostic experiences on ROBIN shall provide the desired experience and database for operations of TWIN and INTF in the coming years. A large number of conventional and advanced diagnostic techniques are used for plasma and beam characterization. These diagnostics are suitable not only to detect and understand the plasma but also for studies related to impurity evolution. The temporal evolution of impurities significantly impacts the plasma and beam properties. The studies help in establishing correlations between physical parameters and operational parameters to optimize the source performance ensuring adequate safety and investment protection. This paper will present a brief overview of various diagnostics implemented, lessons learned, and the results obtained from ROBIN. In addition, an outline of the diagnostics planned for INTF based on the experience and understandings developed during the present experiments on ROBIN and TWIN and considering the requirements of large systems shall be discussed.

Are partners of HIV-infected people being tested for HIV? A mixed-methods research from Gujarat, India.

Setting: Four selected antiretroviral therapy (ART) centres of Gujarat State, India, which accounts for 8% of the human immunodeficiency virus (HIV) burden in India. Objectives: 1) To assess the proportion of people living with HIV (PLHIV) whose partners were not tested for HIV; 2) to assess sociodemographic and clinical characteristics of index cases associated with partner testing; and 3) to understand perceived facilitators and barriers to partner testing and make suggestions on how to improve testing from the perspective of the health-care provider. Design: A mixed-method design with a quantitative phase that involved reviewing the programme records of married PLHIV enrolled during 2011-2015, followed by a qualitative phase of key informant interviews. Results: Of 3884 married PLHIV, 1279 (33%) did not have their partners tested for HIV. Factors including index cases being male, illiterate, aged >25 years, belonging to key populations, substance use and being in advanced clinical stages were more likely to be associated with partner non-testing. Non-disclosure of HIV status (due to fear of marital discord) and lack of awareness and risk perception were the key barriers to testing. Conclusion: One third of PLHIV did not have their partners tested for HIV. Several factors were identified as being associated with the non-testing of partners, and solutions were explored that need to be implemented urgently if we are to achieve the 90-90-90 targets and end HIV.

Contexte : Quatre centres du traitement antirétroviral (TAR) sélectionnés de l'état de Gujarat, qui compte pour 8% du poids du virus de l'immunodéficience humaine (VIH) en Inde.Objective : Nous avons voulu 1) évaluer la proportion de personnes vivant avec le VIH (PVVIH) dont les partenaires n'ont pas été testés pour le VIH ; 2) évaluer les caractéristiques sociodémographiques et cliniques du cas index associées au test du partenaire ; et 3) comprendre les facilitateurs et les contraintes perçus au test du partenaire et faire des suggestions pour améliorer les tests du point de vue des prestataires de soins de santé.Schéma à plusieurs methods: La phase quantitative a impliqué de retrouver dans les archives du programme les PVVIH mariés enrôlés entre 2011 et 2015 ; la phase qualitative a ensuite consisté en entretiens avec des informateurs clés.Résultats: Sur 3884 PVVIH mariés, 1279 (33%) n'ont pas fait tester leurs partenaires pour le VIH. Les facteurs comme le fait que le cas index soit un homme, illettré, d'âge >25 ans, appartenant à des populations clés, utilisant des drogues, étant à un stade avancé de la maladie, ont été plus susceptibles d'être associés à l'absence de test du partenaire. Le non divulgation du statut VIH (due à la peur d'une discorde maritale) et le manque de connaissances et de perception des risques ont été les obstacles majeurs au test.Conclusion : Un tiers des PVVIH n'ont pas fait tester leurs partenaires pour le VIH. Plusieurs facteurs associés à l'absence de test des partenaires ont été identifiés et des solutions ont été recherchées. Elles doivent être mises en œuvre d'urgence si nous voulons atteindre les cibles de 90­90­90 et mettre fin au VIH.

Marco de referencia: Cuatro centros de tratamiento antirretrovírico (TAR) en el estado de Guyarat, que representa el 8% de la carga de morbilidad por el virus de la inmunodeficiencia humana (VIH) de la India.Objetivos: 1) Examinar la proporción de personas positivas frente al VIH cuyas parejas no cuentan con la prueba diagnóstica del VIH; 2) analizar las características socioeconómicas y clínicas del caso inicial que se relacionan con la práctica de la prueba diagnóstica en la pareja; y 3) comprender los elementos facilitadores y los obstáculos percibidos a la prueba del VIH en las parejas y las propuestas encaminadas a mejorar su utilización, desde el punto de vista de los profesionales de salud.Métodos: Se aplicó un modelo de métodos mixtos con una etapa inicial cuantitativa, que comportó el examen de los registros del programa de las personas positivas frente al VIH casadas inscritas del 2011 al 2015, seguida por una etapa cualitativa durante la cual se realizaron entrevistas a informantes clave.Resultados: De las 3884 personas positivas frente al VIH casadas, 1279 parejas no contaban con la prueba del VIH (33%). Las características del caso inicial que se asociaron con mayor frecuencia a la falta de prueba diagnóstica de la pareja fueron el sexo masculino, el analfabetismo, la edad más de 25 años, el hecho de pertenecer a una población clave, el consumo de sustancias psicoactivas y un estadio clínico avanzado de la enfermedad. Los principales obstáculos a la práctica de las pruebas fueron la negativa a divulgar su situación frente al VIH (por temor a una discordia conyugal) y la falta de sensibilización y percepción de los riesgos.Conclusión: En un tercio de las personas positivas frente al VIH, no se había practicado a su pareja la prueba diagnóstica de la infección. Se reconocieron diversos factores vinculados con esta situación y se analizaron las soluciones. La aplicación de estas medidas es urgente con el fin de cumplir con las metas 90­90­90 y eliminar la infección por el VIH.

Multiple delivery cesium oven system for negative ion sources.

Distribution of cesium in large negative ion beam sources to be operational in ITER, is presently based on the use of three or more cesium ovens, which operate simultaneously and are controlled remotely. However, use of multiple Cs ovens simultaneously is likely to pose difficulties in operation and maintenance of the ovens. An alternate method of Cs delivery, based on a single oven distribution system is proposed as one which could reduce the need of simultaneous operation of many ovens. A proof of principle experiment verifying the concept of a multinozzle distributor based Cs oven has been carried out at Institute for Plasma Research. It is also observed that the Cs flux is not controlled by Cs reservoir temperature after few hours of operation but by the temperature of the distributor which starts behaving as a Cs reservoir.

Targeting both Notch and ErbB-2 signalling pathways is required for prevention of ErbB-2-positive breast tumour recurrence.

BACKGROUND: We reported that Notch-1, a potent breast oncogene, is activated in response to trastuzumab and contributes to trastuzumab resistance in vitro. We sought to determine the preclinical benefit of combining a Notch inhibitor (γ-secretase inhibitor (GSI)) and trastuzumab in both trastuzumab-sensitive and trastuzumab-resistant, ErbB-2-positive, BT474 breast tumours in vivo. We also studied if the combination therapy of lapatinib plus GSI can induce tumour regression of ErbB-2-positive breast cancer. METHODS: We generated orthotopic breast tumour xenografts from trastuzumab- or lapatinib-sensitive and trastuzumab-resistant BT474 cells. We investigated the antitumour activities of two distinct GSIs, LY 411 575 and MRK-003, in vivo. RESULTS: Our findings showed that combining trastuzumab plus a GSI completely prevented (MRK-003 GSI) or significantly reduced (LY 411 575 GSI) breast tumour recurrence post-trastuzumab treatment in sensitive tumours. Moreover, combining lapatinib plus MRK-003 GSI showed significant reduction of tumour growth. Furthermore, a GSI partially reversed trastuzumab resistance in resistant tumours. CONCLUSION: Our data suggest that a combined inhibition of Notch and ErbB-2 signalling pathways could decrease recurrence rates for ErbB-2-positive breast tumours and may be beneficial in the treatment of recurrent trastuzumab-resistant disease.

Evaluation of immunomodulatory effect of Ranahamsa Rasayanaya - A Sri Lankan classical rasayana drug, on experimental animals.

Immunity plays a key role in maintaining the health of an individual. Therefore, the rational modulation of the immunity through psycho-neuro-endocrine-immune (PNI) axis is useful for the prevention as well as for the curing of the diseases. As immunomodulation is a parameter for evaluation of the rasayana effect of a drug, the same has been studied to assess the rasayana effect of Ranahamsa Rasayanaya (RR). Experimental models such as antibody formation against sheep red blood cells (SRBC) and cell mediated immunity (CMI) have been carried out befitting on Wistar strain albino rats to determine the immunomodulatory effect plus rasayana effect of RR. Statistically significant increase in body weight, nonsignificant increase in antibody formation against SRBC, highly significant decrease in CMI were observed in the treatment groups, when compared to the standard control group. These results show the probable immunomodulatory and anabolic activities of the test drug. Outcome of these studies validate the strong rasayana effect of the test drug claimed by the traditional practitioners of Sri Lanka.

Evaluation of adaptogenic and anti-stress effects of Ranahamsa Rasayanaya-A Sri Lankan classical Rasayana drug on experimental animals.

Various types of stress not only harm the mental function, but also cause diseases by weakening body defenses. Rasayana therapy has an advantage over the conventional Kayachikitsa treatment in such conditions, as it is capable of counteracting the stress, promote the adaptogenic abilities of the body, enhance mental endurance, etc. These are the some of parameters for evaluation the rasayana effect of a drug, therefore the same have been studied to assess the rasayana effect of Ranahamsa Rasayanaya (RR). Experimental models such as forced swimming induced hypothermia and stress induced gastric ulcer formation have been carried out befitting on Charles Foster strain albino rats to determine the rasayana effect of RR. Statistically highly significant decrease in forced swimming induced hypothermia and non-significant decrease in gastric ulcer formation were observed in the treatment groups, when compared to the stress control group. These results show the probable adaptogenic and anti-stress activities of the test drug. The study results support the claims made by the Sri Lankan traditional practitioners that, the test drug is a potent rasayana formulation.

A short-term intervention trial on HIV positive patients using a Sri Lankan classical rasayana drug - Ranahamsa Rasayanaya.

Rational use of Rasayana therapy, in the management of HIV infected individuals, could potentially stabilize the destructive control mechanisms, by modulating the psycho-neuro-endocrine-immune axis. The objective of the present study has been to determine the short-term effects of Ranahamsa Rasayanaya (RR) in HIV infected patients. A total of 27 patients with documented HIV infection were randomly assigned to two groups, Group A - 5 g of RR twice daily with cow's milk and sugar. Group B - Only routine modern therapy was continued, if any they were taking, including highly active anti-retroviral therapy (HAART). Absolute CD4(+) T-cell and total lymphocyte counts were measured in these patients, registered under Group A. Only 21 participants completed the study protocol (In Group A, 15 patients and in Group B, 6 patients). Initial mean CD4(+) T-cell count was 304.50 ± 43.36 cells/microliter, which increased to 430.44 ± 66.01 cells/microliter by 41.36% (P<0.05), measured among 9 patients out of 15, who received RR in Group A. The RR seemed to be a safer adjuvant in people with HIV infection with respect to absolute CD4(+) T-cell count over a 90 days treatment.

Effect of oral administration of bismuth compounds on Campylobacter colonization in broilers.

Bismuth compounds have been used since the 18th century to treat gastrointestinal ailments in man. Colloidal bismuth subcitrate (De-Nol) is currently used in combination with antibiotics to reduce enteric Helicobacter pylori colonization as a treatment of stomach ulcers. We investigated whether bismuth citrate or its parent compound, colloidal bismuth subcitrate, would reduce colonization of the closely related foodborne pathogen, Campylobacter jejuni in chickens. In 2 studies, birds were either fed 0, 50, or 200 ppm bismuth citrate or bismuth subcitrate (De-Nol) for 10 or 21 d and were orally challenged with 7 combined strains of C. jejuni (n = 6 birds/treatment). For both treatment groups, cecal Campylobacter colonization was reduced when birds were fed 200 ppm for 10 d but not 21 d. For the 50 ppm treatment group, only birds dosed with bismuth citrate for 21 d demonstrated any reduction in cecal Campylobacter concentrations when compared with controls. These data suggest that bismuth citrate and colloidal bismuth subcitrate may reduce cecal colonization by Campylobacter in broilers, but these effects are inconsistent.

Marek's disease virus reactivation from latency: changes in gene expression at the origin of replication.

Marek's disease is a contagious lymphoma of chickens caused by Marek's disease virus (MDV). MDV replicates in chicken lymphocytes and establishes latency within and transforms chicken CD4+ T-cells. Transformed T-cells are seen as skin leukosis or as lymphomas in visceral organs. A major focus of our laboratory is the functional study of genes flanking the origin of replication. This origin (OriLyt) is contained within the repeats flanking the unique long (UL) region of the genome (IRL and TRL). To the left of this Ori are genes associated with MDV latent/transforming infection [1.8-kb RNA family, pp14, Meq), and to the right (UL) are genes associated with early stages of MDV lytic infection [BamHI-H-encoded protein (Hep), pp38/pp24, Mys]. During latency, MDV suppresses lytic gene expression and has evolved mechanisms for blocking the apoptosis of latently-infected CD4+ T-cells. Of the genes expressed during MDV latency and in the transformed cell, the Meq (Marek's EcoRI-Q-encoded protein) has been shown to block apoptosis and transactivate gene expression. Upon reactivation to lytic infection, we have found that splice variants of Meq predominate and that these forms lack several of the domains important to Meq trans-activation and trans-repression. We have found that rightward from the origin of replication, a family genes, including phosphoprotein 38 (pp38) are expressed during early stages of reactivation. Three separate open reading frames (Hep, Mys, and pp38) are encoded by distinct transcripts from this region. We are now determining the kinetics of expression of these transcripts and their relative abundance during reactivation.

Schedule-dependent pulsed paclitaxel radiosensitization for thoracic malignancy.

The objective of this study was to apply preclinical research of paclitaxel radiosensitization to the treatment of thoracic malignancy. Human lung cancer cell line NCI520 and epidermoid cell line A431 were investigated in vitro for radiosensitizing effects of paclitaxel. Optimal schedule of paclitaxel treatment was applied to a clinical protocol as well as off-protocol treatment of thoracic malignancy. Pulsed paclitaxel with concurrent once-daily radiation was delivered every 48 hours during the week using doses of 15 mg/m2, 20 mg/m2, or 25 mg/m2 in a phase I clinical trial of dose escalation. Preclinical data support the finding that low-dose paclitaxel is sufficient for radiosensitization. Data also support that delaying radiation is better than immediate radiation after drug treatment. Twenty-three patients have enrolled in the phase I clinical trial. Seventeen patients completed treatment (6 at 15 mg/m2; 5 at 20 mg/m2; and 6 at 25 mg/m2). Mean tumor shrinkage at 4 to 6 weeks after therapy was 82%, 84%, and 84% for dose levels I, II, and III, respectively [average primary tumor shrinkage was 83% +/- 8% (95% C.I.)]. Locoregional tumor response rate was 100% [12% (2/17) complete response and 88% (15/17) partial response] with low rates of toxicity. It is concluded that pulsed low-dose paclitaxel and radiation is a very effective and well-tolerated regimen for thoracic malignancy.

Plasma analysis of celiprolol by HPTLC: a useful technique for pharmacokinetic studies.

A rapid and sensitive high performance, thin-layer chromatographic (HPTLC) method has been developed for the measurement of celiprolol in human plasma and its use in pharmacokinetic studies has been evaluated. Detection and quantitation were performed without using an internal standard. A simple extraction procedure was followed for extracting celiprolol from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Celiprolol was quantitated using a Camag TLC Scanner 3. The average recovery of authentic analytes (20 to 200 ng/mL) added to plasma was 72.06 +/- 2.8% and the lowest amount of celiprolol that could be detected was 10 ng/mL. The method provides a direct estimate of the amount of celiprolol present in plasma. Pharmacokinetic parameters of 2 marketed preparations have also been determined after oral administration to 12 healthy human volunteers.

Extension of a tuned log spiral of revolution fluorescence XAFS detector, designed for optimal detection of a particular element Z, to XAFS of elements other than Z.

Recently, it has been demonstrated that an x-ray detector in the form of a log spiral of revolution, covered with highly oriented pyrolytic graphite, is an excellent device for obtaining the fluorescence XAFS of an element of interest in the presence of competing fluorescence from other elements. In the present work we investigate the capabilities of a log spiral of revolution (LSR) detector, with a geometry optimized for one element (in this case Cr), if used for XAFS of other elements.

Kinetic controls on Cu and Pb sorption by ferrihydrite.

Metal partitioning in ferrihydrite suspensions may reach equilibrium only after a long reaction time. To determine key factors controlling the kinetics, we measured Cu and Pb uptake as a function of ferrihydrite morphology, reaction temperature, metal competition, and fulvic acid concentration over a period of 2 months. X-ray microscopy, which was used to probe ferrihydrite morphology in suspension, showed that drying irreversibly converted the gellike structure of fresh precipitate into dense aggregates. These dense aggregates sorbed Cu and Pb much slower than the gel. Temperature had a more pronounced effect on the kinetics of metal uptake by ferrihydrite gel than by dense ferrihydrite. Independently of treatment and time, Cu and Pb were bound to the ferrihydrite surface byformation of edge-sharing inner-sphere sorption complexes as confirmed by X-ray absorption fine-structure (XAFS) spectroscopy. This invariable binding mechanism, together with the observed effects of morphology and temperature, are in line with surface diffusion limiting the slow sorption process. The quantification of diffusion-limited surface sites in soils and sediments and the subsequent estimation of the effect of reaction time and temperature will be a challenge for properly predicting the fate of metals in the environment.

Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882).

To investigate the effect of adding tamoxifen to megestrol in the hormonal therapy for advanced endometrial cancer, 66 patients were entered in this study. Initially, 41 patients were randomized to either the standard progestin therapy of megestrol or to the combination of megestrol and tamoxifen between October 1982 and October 1984. The megestrol arm was terminated because of poor accrual and 25 patients were directly assigned to the combination arm. Among the 20 eligible cases on the megestrol arm, the response rate of 20% consisted of I complete response and 3 partial responses. The response rate on the megestrol plus tamoxifen arm was 19% with 1 (2%) complete response and 7 (17%) partial responses among 42 eligible cases. The median survival times were 12.0 months and 8.6 months, respectively. Only mild and moderate toxicities were observed on megestrol compared with more toxic complications observed on the combination of megestrol and tamoxifen, including a life-threatening case of pulmonary embolism. Although we could not carry out a comparative evaluation as intended, we conclude that the combination of megestrol and tamoxifen offers no clinical advantage over megestrol alone in the treatment of advanced endometrial carcinoma.

Novel transactivation domain in erythroid Kruppel-like factor (EKLF).

Erythroid Kruppel-like Factor (EKLF) is an erythroid-specific transcription factor that plays a critical role in gamma- to beta-globin gene switching during development. To identify essential domains required for EKLF transactivation function, we cotransfected a human erythroleukemia cell line (K562) with a locus control region gamma/Luc-beta/Cat reporter and an EKLF expression vector. In this assay EKLF mediates a 500-fold induction of beta/CAT expression compared with controls. To map essential transactivation domains, progressive NH(2)-terminal and internal deletion mutants of EKLF were constructed. All EKLF mutants were expressed at wild-type levels, localized to the nucleus, and bound DNA. When mutant EKLF proteins were tested for beta/CAT activation, a novel transactivation domain was identified. This novel domain, encompassing amino acids (aa) 140-358, is sufficient for maximal beta/CAT activation. An 85-amino acid subdomain within this region (aa 140-225) is essential for its activity. Interestingly, this central transactivation subdomain is functionally redundant with the amino-terminal domain (aa 1-139). Thus, EKLF possesses at least two potent transactivation domains that appear to function in a redundant manner.

Phase II trial of cisplatin, etoposide, and 5-fluorouracil in advanced non-small-cell lung cancer: an Eastern Cooperative Oncology Group Study (PB586).

Advanced non-small-cell lung cancer (NSCLC) remains an incurable disease despite significant progress in chemotherapy. We conducted a phase II clinical trial to investigate the efficacy and toxicity of a cisplatin, etoposide, and 5-fluorouracil (5-FU) combination in advanced metastatic and/or recurrent NSCLC. Forty patients with advanced, recurrent, or metastatic, measurable NSCLC were treated with cisplatin, 60 mg/m2 intravenously (i.v.) on day 1; etoposide, 120 mg/m2/day i.v. on days 1, 2, and 3; and 5-FU. 1,000 mg/m2/day i.v. continuous infusion on days 1 through 5. Treatment was administered in 4-week cycles. Thirty patients had distant metastases and were previously untreated, and 10 patients had recurrent disease after prior treatment with either surgery (1 patient), radiation therapy (5 patients), or both treatments (4 patients). Twenty-nine patients were evaluable for response. Seven (24%) patients achieved a partial remission (PR), 18 (62%) had stable disease (SD), and 8 (14%) had progressive disease (PD). Overall median survival was 7.9 months (range, 0.4-27.4 months). Patients who achieved a PR had a median survival of 23.5 months (9.3-27.4 months). In contrast, patients with SD had a median survival of 9.9 months (2.5-25.3 months), and patients with PD had a median survival of 2.1 months (1-9.3 months). Median duration of response of 27.1 weeks (4.9-76.5 weeks) for patients with PR, and time to progression was 13.4 weeks (3.7-54.5 weeks) for patients with SD. Toxicity was primarily hematologic and gastrointestinal, and there were three deaths due to infection. The combination of cisplatin, 5-FU, and etoposide as administered in this study appears to have considerable toxicity and does not appear to be superior to other cisplatin-containing regimens used for the treatment of advanced NSCLC.

21-day oral etoposide for metastatic breast cancer: a phase II study and review of the literature.

Previous studies of etoposide for metastatic breast cancer commonly used bolus regimens given over a short period of time and included heavily pretreated patients. Results were poor. Chronic oral regimens would be expected to be superior to bolus doses based on pharmacologic studies and patients with less previous chemotherapy would be expected to have higher response rates. We studied the efficacy of oral etoposide at a dose of 50 mg/m2/day for 21 days of a 28-day cycle in good-risk patients with metastatic breast cancer. Healthy patients (Eastern Cooperative Oncology Group performance status 0, 1, or 2) who had not received chemotherapy for at least 1 year before study entry were selected for therapy. Thirty-four patients were entered; three patients were ineligible and one was cancelled. Thirty patients were available for analysis of response. One complete response and eight partial responses were documented (response rate, 30%; 95% confidence interval, 15-49%). A higher response rate was observed in those patients who never received chemotherapy compared with those who had received prior chemotherapy (57 vs. 6%, p = 0.004). There were two treatment-related deaths, both owing to myelosuppression and infection. We found long-term administration of oral etoposide to have a reasonable response rate for metastatic breast cancer (30%). Our response rate was comparable to those of other published studies of long-term oral etoposide regimens for metastatic breast cancer. Response rates in single-arm studies have generally been higher for long-term oral regimens than those for bolus regimens. We also found the regimen to be significantly toxic, an observation that may be underemphasized in the earlier literature.