Sequential Monotherapy Research Articles

A Combination anti-HBV regimen using lamivudine and other agents in treatment of resistant chronic hepatitis B

Background: Several difficulties remain in formulating treatment for chronic hepatitis B (CHB), 350 million people are chronically infected with HBV, Chronic infection with hepatitis B virus accounts for an enormous burden of disease worldwide, including up to half of all cases of cirrhosis, end stage liver disease , and hepatocellular carcinoma. Aim of the work: To maximize the elimination of the viral infection while minimizing or preventing damage to the liver cells and tissues and development of viral resistance to more antivirals. Patients and Methods: Eighty eight patients of chronic hepatitis B virus infection with resistance to lamivudine treatment as proved by quantitative PCR (more than 200 IU/ ml). Their age between (20-60) years, (85 males, and 3 females) were selected from the National Hepatology and Tropical Medicine Research Institute and were included in this study. The included patients were two groups, the first group 42 patients , were receiving Lamivudine, plus (Baraclude) Entecavir (tablet 0.5mg / day) treatment at the time of assessment. The second group 46 patients were receiving ( Hepsera tablet 10 mg / day ) Adefovir dipivoxil plus lamivudine (tablet). All the patients were subjected to the following : thorough history and clinical examination, abdominal ultrasonography and collection of blood samples for routine liver and kidney function investigations and serological assay for HBsAg, HBsAb, HBeAg, HBeAb, HBcAb quantitative HBV DNA (PCR). Results: Our results revealed significant differences between the two groups of patients of CHBV infection, resistant to Lamivudine drug, the first group were higher in response to a combination between Lamivudine + (Baraclude) Entecavir, than the second group who were receiving Lamivudine + (Hepsera) Adefovir dipivoxil combination therapy. Conclusion: Our study concluded that the clinical benefit is apparent with high percentage after a combination regimen using Lamivudine + Entecavir than a combination regimen using Lamivudine + Adefovir dipivoxil for the treatment of resistant chronic hepatitis B virus who were treated with Lamivudine only before. Recommendations: Optimal management of chronic hepatitis B,that may require long-term and sometimes lifelong treatment to maintain its clinical benefit is challenging. It is important to initiate treatment with a drug that has the least potential for induction of drug resistance as sequential monotherapy which may result in selection of multidrug resistant HBV mutatants.

Successful treatment of methicillin-resistant Staphylococcus aureus mitral valve endocarditis with sequential linezolid and telavancin monotherapy following daptomycin failure--authors' response

Successful treatment of methicillin-resistant Staphylococcus aureus mitral valve endocarditis with sequential linezolid and telavancin monotherapy following daptomycin failure--authors' response

Comparing Treatment of Neovascular Age-related Macular Degeneration with Sequential Intravitreal Avastin and Macugen Versus Intravitreal Mono-therapy–A Pilot Study

Purpose: To examine if the sequential treatment of Avastin and Macugen is safe and more efficient than the mono-therapies in a prospective randomized masked pilot study.Materials and Methods: Subjects with exudative age-related macular degeneration were randomized to receive three intravitreal injections of either 1 mg of Avastin, 0.3 mg Macugen, or first 1 mg Avastin followed by retreatment of 0.3 mg Macugen. Follow-up examinations were performed after 1, 6, 12 weeks, and 6 months.Results: Forty-eight subjects were included (13:18:17). Avastin resulted in lasting significant changes in visual acuity at 6 weeks, increase in contrast sensitivity at 6 weeks, and a significant decrease in macular thickness after 6 and 12 weeks. Macugen showed a significant decrease in retinal thickness after 6 weeks, but a significant decrease in visual acuity after 6 months, and a significant decrease in contrast sensitivity after 12 weeks and 6 months. The sequential treatment showed a decrease in retinal thickness after 1 and 12 weeks.Conclusion: Avastin alone is more effective in increasing visual acuity and contrast sensitivity and decreasing retinal thickness, than Macugen or the sequential treatment. We conclude that the sequential treatment of Avastin with Macugen is safe, but the single treatment of Avastin is more efficient.

Parental preferences for treatment: Preliminary report from a randomised comparison of treatment strategies in (early) juvenile idiopathic arthritis (BeSt for Kids trial)

Methods A questionnaire is taken at the start in all parents of the participants of the BeSt for Kids trial, treated with either initial sequential monotherapy (group 1) with either methotrexate or sulfasalazine, initial combination therapy with methotrexate and tapered prednisone (group 2), or initial combination therapy with methotrexate and etanercept (group 3). ACRp50 is the primary goal, treatment adjustments are made every 3 months to aim at clinical remission on medication from 6 months and onwards. The questionnaire explores parental preferences or dislikes for the initial therapy.

Phase II clinical trial with gemcitabine and paclitaxel sequential monotherapy as first-line treatment for advanced non-small-cell lung cancer (SLCG 01-04)

In advanced-stage (IIIB or IV) non-small-cell lung cancer (NSCLC), combination chemotherapy has demonstrated response rates of 20% and a 1-year survival rate of 30%. We conducted a multicentre, open-label, nonrandomised phase II trial to determine the efficacy and tolerability of sequential monotherapy with gemcitabine followed by paclitaxel in chemotherapy-naïve patients with advanced NSCLC. Between December 2002 and July 2004, the Spanish Lung Cancer Group (SLCG) conducted a study in which 34 patients with advanced (stage IIIB or IV) NSCLC received 1200 mg/m(2) of i.v. gemcitabine on days 1, 8 and 15 of each 28-day cycle for a total of 3 cycles followed by 100 mg/m(2) of weekly i.v. paclitaxel for a maximum of 8 weeks. If objective response or stable disease was achieved, 70 mg/m(2) of weekly i.v. paclitaxel was maintained until disease progression was evident or toxic effects were intolerable. Lung Cancer Symptom Scale (LCSS) analysis was performed. Baseline levels of serum VEGF, EGFR, telomerase reverse transcriptase (hTERT) and K-ras mutations were analysed. The primary endpoint was the objective response rate. The median age of the 34 patients who were enrolled was 67 years (range 46-77), but later 8 patients were excluded; 78.8% were men, 81.8% had performance status 1 and also 81.8% had metastatic disease at diagnosis. The objective response rate was 28% (95% CI, 14.2-47.8); the median overall survival was 7.2 months (95% CI, 2.1-12.3) and the median time to progression (TTP) was 3.1 months (95% CI, 2.5-5.3). Grade 3 or 4 drug-related haematological toxicities were observed in 6 patients. Patients with lower baseline serum VEGF levels had significantly longer survival. Sequential therapy with gemcitabine followed by paclitaxel was well tolerated with a low proportion of grade 3 or 4 adverse events, the absence of unexpected toxicity and with an improvement in quality of life. Unfortunately, the response rate did not meet the minimally required rate of 20% and the study was prematurely closed. VEGF was identified as a poor prognostic factor for TTP and survival.

Anti-TNF therapy: what have we learned in 12 years?

Two decades ago, the available treatment options were not effective for many persons with rheumatoid arthritis (RA) and other inflammatory rheumatic diseases. At this time RA patients had a significantly decreased life expectancy due to a relatively incontrolled inflammatory activity of RA combined with an increased incidence of comorbidities and severe treatment-related side effects. After 5 years of disease duration, a considerable percentage of patients became unemployed. The available disease-modifying antirheumatic drugs were able to slow disease progression, but they could not stop it. This unsatisfying situation changed significantly at the beginning of the 1990s, when treatment options for RA patients expanded to include TNF blockers. These blockers were shown to significantly decrease not only the inflammatory activity of RA, but also the radiographic progression. This breakthrough in therapeutic options was fostered by the pioneering research of Prof. Sir Ravinder Maini and Prof. Sir Marc Feldman working at the Kennedy Institute in London, who introduced a chimeric monoclonal antibody against TNFα in the treatment of RA patients. Since these early clinical trials, TNF inhibitors have radically changed the entire therapeutic approach, not only for RA but also for ankylosing spondylitis (AS) and for psoriatic arthritis (PsA). While the focus once was symptom mitigation, rheumatologists now seek control of disease progression. Today, TNF inhibitors effectively suppress and control the inflammation driving these diseases, and thereby prevent irreversible tissue damage and disability. Radiographic studies are showing that progressive joint damage can be halted under certain conditions in some patients. These conditions and patients are currently being elucidated. New frontiers include early diagnosis and referral; optimizing treatment regimens; identifying patients at risk of rapidly progressing disease; and instituting early, rapid TNF blockade in these patients. Using combination therapy with TNF inhibitors and disease-modifying antirheumatic drugs – specifically methotrexate – at an early stage of RA, disease progression can be stopped or at least significantly retarded. The four articles in this supplement present up-to-date information, current data, and the best thinking on anti-TNF therapy in RA, AS, and PsA. Since research over the past decade revealed that these three disorders share an inflammatory mechanism fueled especially by TNF, efforts to produce viable TNF inhibitors have accelerated. Josef S Smolen and Paul Emery, in their article ‘Infliximab: 12 Years of Experience’, expound upon the record of efficacy and safety amassed for this TNF inhibitor. Research on infliximab, which began with the first randomized controlled study in a rheumatic disease, stimulated most of the development of TNF neutralizing therapies. The authors summarize the major trials in RA, AS, and PsA that contributed to this body of evidence. In the second article, ‘Understanding Emerging Treatment Paradigms in Rheumatoid Arthritis’, Ferdinand C Breedveld and Bernard Combe assert that most patients with RA are undertreated. They outline accumulating data showing that intensive treatment in the early stages of RA can slow or stop disease progression, and they describe alternatives to traditional step-up approaches and to sequential monotherapy with disease-modifying antirheumatic drugs. Next, Georg Schett and colleagues focus on bone and cartilage injury in all three diseases, with an emphasis on key knowledge arising from TNF research and how it has paved the way for future advances. Their article, ‘Structural Damage in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis: Traditional Views, Novel Insights Gained from TNF Blockade, and Concepts for the Future’, explores the different pathologies as well as radiographic data for the interaction between inflammation and structural progression. Lastly, Paul P Tak and I discuss innovative approaches – with TNF inhibitors but also with other biologic agents – to inflammatory arthritides, including new targets within the inflammatory cascade, agents designed to affect associated pathways, and improved management strategies involving early diagnosis and referral. In the article ‘Advances in Rheumatology: New Targeted Therapeutics’, we explore the variable response to targeted therapy and consider how best to integrate these advanced therapies into daily practice. Our goal with the present supplement is to provide a valuable, current resource from which additional dialog may spring. We all agree that optimal treatment, initiated sooner, may reduce costs and risks to patients, and therefore achieve our common ambition – to help the patient and to attain low disease activity or remission in persons with inflammatory arthritis.

Randomized Phase II Study Comparing Efficacy and Safety of Combination-Therapy Trastuzumab and Docetaxel vs. Sequential Therapy of Trastuzumab Followed by Docetaxel Alone at Progression As First-Line Chemotherapy in Patients with HER2 + Metastatic Breast Cancer: HERTAX Trial

Background Because chemotherapy for metastatic breast cancer (MBC) is associated with relevant toxicity, sequential monotherapy trastuzumab followed by cytotoxic therapy at disease progression might be an attractive approach. Methods In a multicenter phase II trial, 101 patients with overexpression of human epidermal growth factor receptor 2 (HER2 +) MBC were randomized between combination-therapy trastuzumab (Herceptin) plus docetaxel (H+D) and sequential therapy of single-agent trastuzumab followed at disease progression by docetaxel alone (H→D) as first-line chemotherapy for metastatic disease. The primary endpoint was progression-free survival (PFS) after completed sequential or combination therapy. Results For the H+D group the median PFS was 9.4 vs. 9.9 months for the H→D group and 1-year PFS rates were 44% vs. 35%, respectively. However the overall response rates (ORRs) were 79% vs. 53%, respectively ( P = .016), and overall survival was 30.5 vs. 19.7 months, respectively ( P = .11). In the H→D group, response rates to monotherapy trastuzumab and subsequent docetaxel were 34% and 39%, respectively, with a median PFS during single-agent trastuzumab of 3.9 months. The incidence and severity of neuropathy were significantly higher in the H+D group. Retrospective analysis of trastuzumab treatment beyond progression (applied in 46% of patients in the H+D group and 37% in the H→D group) showed a correlation with longer overall survival in both treatment arms (36.0 vs. 18.0 months and 30.3 vs. 18.6 months, respectively). Conclusion First-line treatment in patients with MBC with H→D resulted in a similar PFS compared with H+D, but the response rate was lower and the overall survival nonsignificantly shorter.

Spontaneous Emergence of Multiple Drug Resistance in Tuberculosis before and during Therapy

The emergence of drug resistance in M. tuberculosis undermines the efficacy of tuberculosis (TB) treatment in individuals and of TB control programs in populations. Multiple drug resistance is often attributed to sequential functional monotherapy, and standard initial treatment regimens have therefore been designed to include simultaneous use of four different antibiotics. Despite the widespread use of combination therapy, highly resistant M. tb strains have emerged in many settings. Here we use a stochastic birth-death model to estimate the probability of the emergence of multidrug resistance during the growth of a population of initially drug sensitive TB bacilli within an infected host. We find that the probability of the emergence of resistance to the two principal anti-TB drugs before initiation of therapy ranges from 10−5 to 10−4; while rare, this is several orders of magnitude higher than previous estimates. This finding suggests that multidrug resistant M. tb may not be an entirely “man-made” phenomenon and may help explain how highly drug resistant forms of TB have independently emerged in many settings.

The impact of four dynamic, goal-steered treatment strategies on the 5-year outcomes of rheumatoid arthritis patients in the BeSt study

ObjectiveTo compare clinical and radiological outcomes of four dynamic treatment strategies in recent-onset rheumatoid arthritis (RA) after 5 years follow-up.Methods508 patients with recent-onset RA were randomly assigned into four treatment...

Characterization of hepatitis virus B isolated from a multi-drug refractory patient

Prolonged treatment of chronic hepatitis B (CHB) with nucleoside analogues (NAs) almost invariably engenders viral resistance, and sequential NAs monotherapy can promote multi-drug resistance. This study aimed to investigate the molecular characteristics and the mutation profile of multi-drug resistant hepatitis B virus (HBV). The complete genome of HBV isolated from a multi-drug refractory patient was amplified and cloned, and 22 clones were selected for sequencing. The homology of the full-length genome between clones ranged from 98.7% to 99.9%. A precore stop codon mutation of G1896A and basic core promoter (BCP) mutations A1762T/G1764A were detected in a majority of clones. A phylogenetic analysis showed that all clones were classified as subgenotype B2. Three mutations in the surface (S) antigen region, sC76Y, sP120T and sI195M, were detected in 100%, 100% and 77.3% of the clones, respectively. In the core (C) antigen region, a mutation at codon 135 (cP135Q) was detected in 100% of clones. Lamivudine (LAM)-resistant mutations, rtL180M and rtM204V/I were detected in 86.4% of clones. Adefovir (ADV) or entecavir (ETV)-resistant mutations were not detected. Several novel mutations, such as rtT128N, rtA222T, rtS256G, rtL271M, rtS332R, and rtN/T337D, were present in a majority of clones. Furthermore, six pairs of mutations in the overlapping reverse transcriptase (RT) gene and S gene were detected. In conclusion, the complex HBV mutation profile detected in the multi-drug refractory patient highlights the problems associated with the ongoing selection of mutations, including further compensatory mutations as well as potential cross-resistance mutations.

Fixed-dose combination and chronic kidney disease progression: which is the best?

Use of combination therapy whether fixed dose or separate pill combinations is becoming more prevalent. Physicians are not routinely trained in using combinations of different antihypertensive medicines. Recent outcome trials as well as smaller studies document that meaningful combinations of pharmacologically additive agents help achieve blood pressure (BP) goals faster and reduce outcomes. Clinical trials demonstrate that drugs interfering with the renin-angiotensin system, that is, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, combined with either calcium antagonists or thiazide-like diuretics and used as first-line antihypertensive therapy in patients whose BP is more than 20/10 mmHg above goal achieve BP goal faster than sequential monotherapy. Additionally, certain combinations may provide better cardiovascular outcomes than other combinations. Lastly, combination therapy has a clear role in helping to reduce cardiovascular and renal risk, when used. This review provides an update of current evidence regarding the associations of BP control with use of combination antihypertensive therapy to achieve BP goals. A rationale for initial single pill and fixed-dose combination therapy is reviewed. Only one trial with cardiovascular outcome has been performed using a fixed-dose combination and this revealed differences from other trials, including the greatest number of people achieving goal BP and difference in outcomes based on combination used.

Optimising the strategy of care in early rheumatoid arthritis

In rheumatoid arthritis (RA), early use of disease-modifying anti-rheumatic drugs (DMARDs), intensive follow-up and 'treating to target' to achieve low disease activity produce significant improvements in measures of disease activity, functional impairment and retard erosive radiographic progression. Step-up, parallel and step-down regimens are all significantly more effective than sequential monotherapy; although the most effective regimen has not been established. Minimising the period of exposure to synovitis, by including a rapidly acting agent (e.g., corticosteroids or tumour necrosis factor alpha (TNFalpha) inhibitor), may slow radiographic progression further. Biologic therapies, especially TNFalpha inhibitors, are effective in early RA; however, their exact role is unclear. Current measures may overestimate the number of patients in clinical remission; therefore, musculoskeletal ultrasound and/or novel biomarkers may also have a role. Pre-clinical immunological markers could possibly be used to trigger pre-emptive treatment in asymptomatic, 'at risk' individuals. Potential treatment developments include combining biologic agents or targeting alternative immunological pathways.

Time to Achieve Blood Pressure Goal with a Combination Versus a Conventional Monotherapy Approach in Hypertensive Patients with Metabolic Syndrome

The time to achieve a blood pressure (BP) goal ≤130/85 mmHg with a combination versus a conventional monotherapy approach was evaluated in 308 hypertensive patients with metabolic syndrome. They were randomized to valsartan (V) 8 mg/amlodipine (A) 5 mg combination or to V 160 mg monotherapy for 12 weeks and every 2 weeks, there was a titration in nonresponder patients: in the combination group V/A was progressively increased to V 160/A 5 mg; V160/A 7.5 mg; V160/A 10 mg; V 240/A 10 mg, and V 320/A 10 mg. In the monotherapy group, the regimen was progressively modified as following: V 240 mg; V 320 mg; V 320/A 5 mg; V 320/A 7.5 mg, and V 320/A 10 mg. The mean time to achieve the BP goal was shorter in patients randomized to combination therapy compared to those randomized to conventional monotherapy (4.7 ± 2.7 weeks vs. 7.1 ± 3.9 weeks, respectively, p < 0.001). The percentage of patients who achieved target BP in the combination approach group statistically exceeded that of the monotherapy treated one already after 2 weeks of treatment (30.5 vs. 14.9%, p < 0.01) and again after 4, 6, 8, and 10 weeks of treatment. Only at 12 weeks the percentage of normalized patients was similar in the two treatment groups (78.8% vs. 75.3%, ns). These results suggest that initial therapy with a V/A combination approach may be more quickly effective than a conventional sequential monotherapy approach in achieving target BP in hypertensive patients with metabolic syndrome.

Optimizing Blood Pressure Control in Patients with Chronic Kidney Disease

The majority of patients with chronic kidney disease have hypertension, which is an independent risk factor for progression of kidney disease and cardiovascular disease. Therefore, hypertension should be stringently controlled to a blood pressure level of <130/80 mm Hg. Achieving this goal, which usually requires two or more antihypertensive agents, slows the progression of kidney disease and reduces the risk of cardiovascular disease. All antihypertensive treatments for patients with chronic kidney disease should include a renin-angiotensin-aldosterone system (RAAS) inhibitor (an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker). Initial therapy with fixed-dose RAAS inhibitor–based combinations should be considered, because this approach has been shown to bring significantly more patients to target blood pressure levels, compared with stepped-care treatment or sequential monotherapy. Fixed-dose combination therapy may also improve patient adherence to treatment by reducing the number of pills taken daily and the number of office visits for dosage adjustments. Recent clinical data suggest that the combination of a RAAS inhibitor and a dihydropyridine calcium channel blocker may provide more cardiovascular benefit than the generally recommended combination of a RAAS inhibitor and a diuretic in patients at high risk for cardiovascular events.

First-line everolimus followed by second-line sunitinib versus the opposite treatment sequence in patients with metastatic renal cell carcinoma (mRCC).

TPS232 Background: Targeted therapies for advanced renal cell carcinoma (RCC) have changed treatment paradigms. Currently, sequential monotherapy with targeted agents is the standard of care. Sunitinib is a multikinase inhibitor approved for first-line use in advanced RCC; everolimus, an oral inhibitor of mTOR, is approved for use following sunitinib. Currently, these 2 agents have level 1 recommendations for use in the first and second line settings, respectively. However, the most appropriate sequence for everolimus and sunitinib has not been established in a prospective clinical trial. The RECORD-3 (Renal Cell Cancer Treatment with Oral RAD001 Given Daily) trial will assess progression-free survival (PFS) for everolimus- sunitinib versus sunitinib-everolimus in treatment naive patients with mRCC. RECORD-3 is the first trial to evaluate everolimus as second-line therapy after treatment solely with sunitinib. Methods: RECORD-3 is a randomized, open-label, multicenter phase II trial currently recruiting p...

Combination versus sequential chemotherapy for metastatic breast cancer: An evaluation of outcomes from a community oncology network.

6106 Background: There is wide variability in the treatment of metastatic breast cancer (MBC). Debate exists regarding the relative benefits of combination vs. sequential chemotherapy. Combination therapy may improve response rates, but its effect on overall survival (OS) is not clear. This study evaluated OS for MBC patients receiving combination vs. sequential therapy starting with second-line therapy. Methods: Using the iKnowMed electronic medical record database from the US Oncology network, patients with MBC who initiated second-line chemotherapy between July 2006 and July 2009 were included in this retrospective analysis. Combination therapy was allowed in all patients for first-line therapy only. Group A patients were treated with sequential single-agent chemotherapy (other than first-line). Group B patients received combination chemotherapy at any time beyond first-line. The primary endpoint was OS (from time of initiation of second-line chemotherapy to death). A documented date of death was required for inclusion. Patients with HER2-positive disease were excluded. Patients were characterized with respect to age, Karnofsky performance status, hormone receptor status, visceral vs. bone-only metastases, and lines of therapy. OS was compared using the Kaplan Meier method. Results: 263 patients were included. 135 patients received single-agent therapy (Group A) and 128 patients received combination therapy (Group B). There was a 1.1 month difference in median OS, which was not significant (6.5 months in Group A vs. 7.6 months in Group B; p = 0.1493; hazard ratio = 0.8356; 95% CI = 0.6550 to 1.0665). The groups were well balanced with respect to age, hormone receptor status, and types of metastases. Patients receiving combination therapy tended to have slightly higher performance status. Median number of lines of therapy for MBC was 3 (Group A) vs. 4 (Group B). Conclusions: These findings, incorporating real-world variability in the treatment of MBC, support the concept that combination chemotherapy beyond first-line does not significantly prolong survival compared to sequential monotherapy. Because MBC is incurable, OS, toxicities, and costs are important treatment considerations. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration US Oncology

Blood pressure changes in patients with recent-onset rheumatoid arthritis treated with four different treatment strategies: a post hoc analysis from the BeSt trial

ObjectiveTo evaluate the effect of disease activity and antirheumatic treatment on blood pressure (BP) in patients with recent-onset rheumatoid arthritis (RA).Methods508 patients with RA were randomised to receive (1) sequential...

Clinical audit: virological and immunological response to combination antiretroviral therapy in HIV patients at a Sydney sexual health clinic

Bigge Park Centre (BPC) is a sexual health clinic located in a socially disadvantaged area in Southwest Sydney. This served as a retrospective clinical audit, documenting patient demographics, identifying factors associated with virological, immunological and discordant responses, evaluating the centre's ability in HIV control and investigating changes in practice from 1996 to 2007. Data including age, gender, ethnicity, mode of transmission, hepatitis co-infection, prior acquired immune deficiency syndrome (AIDS)-defining-illness, HIV-1 RNA and CD4+cell counts of patients on combination antiretroviral therapy (CART) for treatment of HIV with at least 1-year follow up at the BPC were analysed. Results were compared with other cohorts in medical literature. BPC manages HIV patients from diverse backgrounds. Sequential monotherapy was associated with poor virological control, lower CD4+cell recovery and discordant response. When patients who had sequential monotherapy were excluded, Caucasian race, high viral load at 1 month and triple-NRTI (nucleoside reverse transcriptase inhibitor) regimen were associated with lack of virological control. Lower baseline viral load and triple-NRTI regimen were associated with lower CD4+cell recovery. Lower baseline CD4+cell count and prior diagnosis of AIDS were associated with discordant response. Virological control and CD4+cell recovery achieved were comparable to that documented in medical literature. There was no significant change over time in terms of timing of CART initiation, attainment of immunological response or virological control since the late 1990 s. HIV control achieved at the BPC was comparable to that reported in medical literature. Enhancement of strategies to promote screening and improve adherence as well as performance of HIV resistance assessment and avoidance of triple-NRTI therapy will likely improve patient care.

Evolution of endocrine adjuvant therapy for early breast cancer

Endocrine treatment plays a pivotal role in the adjuvant therapy of patients harbouring oestrogen and/or progesterone receptor positive breast cancer. The objective of this paper is to critically review endocrine treatment options in early breast cancer focusing on ongoing development. Literature was collected through the ISI Web of Science and PubMed in January/February 2009 with subsequent update by December 2009, using the words breast cancer, endocrine therapy, oestrogen receptor and aromatase. Endocrine therapy improves outcome in early breast cancer. Yet several controversies remain. There has recently been a lack of general consensus regarding the limit of oestrogen receptor positivity. As for adjuvant therapy in general and use of aromatase inhibitors in particular, we need the results from ongoing studies to decide what may be the optimal duration of therapy and regimen (sequential treatment versus monotherapy; one drug compared with another). Further, there is a need to critically assess optimal use of endocrine therapy for metastatic disease among patients previously exposed to endocrine regimens in the adjuvant setting. While in general the mechanisms of resistance to endocrine therapy among ER positive tumours remains unknown, merging evidence suggest a role of different growth factor pathways, in particular HER-2 activation. Thus, particular attention is paid to the topic of HER-2 expression as a potential cause of endocrine resistance.

Outcomes in paediatric metastatic rhabdomyosarcoma: Results of The International Society of Paediatric Oncology (SIOP) study MMT-98

Purpose Results are presented of the SIOP study MMT-98 for paediatric metastatic rhabdomyosarcoma (RMS), which evaluated intensive chemotherapy followed by low intensity ‘maintenance’ chemotherapy in standard risk patients (SRG). For poor risk patients (PRG), the value of a therapeutic window study, sequential high dose monotherapy to achieve a complete response (CR) followed by low dose maintenance chemotherapy was examined. Patients and methods From November 1998 to 2005, 146 patients aged 6 months to 18 years with metastatic RMS were entered. Forty-five were SRG, i.e. age < 10 years and no bone marrow or bone involvement. Treatment was a 6-drug regimen with local therapy of surgery and/or radiotherapy followed by maintenance of 9 courses of vincristine, actinomycin D and cyclophosphamide (VAC). One hundred and one patients were PRG, i.e. >10 years, or with bone marrow or bone metastases. An upfront window study, high dose monotherapy, local treatment and then VAC maintenance therapy were given. Results With a median follow-up of 1.52 years, the 3-year event-free survival (EFS) and overall survival (OS) for SRG were 54.92% and 62.14%, respectively, whilst for the PRG 16.17% and 23.17%. The corresponding adverse hazard ratio (HR) for the PRG was HR = 2.65 (95% CI 1.63–4.31, p-value < 0.001) for EFS and HR = 2.51 (CI 1.53–4.11, p-value < 0.001) for OS. Conclusion SRG patients’ EFS and OS were comparable to those of previous studies. For PRG patients there was no improvement in survival.