The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer.

BACKGROUND: To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy. METHODS: Baseline clinical prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis. RESULTS: NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 [P < 0.001, hazard ratio (HR) 2.04], pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis. CONCLUSIONS: We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC.

Clinical outcomes to pemetrexed-based versus non-pemetrexed-based platinum doublets in patients with KRAS-mutant advanced non-squamous non-small cell lung cancer.

PURPOSE: KRAS mutation has been associated with enhanced dependency on the folate metabolism in preclinical studies. However, whether KRAS mutation correlates to increased sensitivity to pemetrexed in patients with advanced NSCLC is unknown. METHODS: Patients with advanced non-squamous NSCLC who had a documented EGFR and ALK WT genotype with simultaneous KRAS mutation assessment were evaluated for clinical outcome to pemetrexed- and non-pemetrexed-based first-line platinum doublet according to KRAS mutation status. RESULTS: Of 356 patients identified, 138 harbored a KRAS mutation. Among KRAS-mutant NSCLCs, those treated with platinum/pemetrexed (81/138) had significantly lower ORR (30.9% versus 47.4%, P = 0.05), DCR (51.8% versus 71.9%, P = 0.02) and shorter median progression-free survival [mPFS 4.1 versus 7.1 months, HR 1.48 (95% CI 1.03-2.12), P = 0.03] and median overall survival [mOS 9.7 versus 26.9 months, HR 1.93 (95% CI 1.27-2.94), P = 0.002] compared to those who received a non-pemetrexed-based platinum doublet (57/138). No difference in ORR, DCR, mPFS and mOS was observed between KRAS WT patients who received a pemetrexed-based (124/218) versus non-pemetrexed base platinum doublets (94/218). After adjusting for performance status, age and the presence of brain metastasis at baseline, treatment with pemetrexed-based platinum doublet was associated with an increased risk of death [HR 2.27 (95% CI 1.12-4.63), P = 0.02] among KRAS-mutant patients in multivariate analysis. CONCLUSION: Patients with KRAS-mutant lung adenocarcinoma have a poorer outcome on pemetrexed-based first-line chemotherapy. Whether KRAS-mutant NSCLCs should be excluded from pemetrexed-containing regimens should be assessed prospectively.

Osimertinib beyond disease progression in T790M EGFR-positive NSCLC patients: a multicenter study of clinicians' attitudes.

BACKGROUND: In most cases, T790M EGFR-positive NSCLC patients receiving osimertinib developed "non-drugable" progression, as the patients with common EGFR-sensitizing mutations were treated with first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression. METHODS: We conducted a study on "post-progression" (pp) outcomes of T790M EGFR-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), "switched therapies" or best supportive care only (BSC). RESULTS: 144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression [19 (20.9%) of them with adjunctive LATs] and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively [HR 0.57 (95% CI 0.35-0.92), p = 0.0239] and 11.3 months vs 7.8 months, respectively [HR 0.57 (95% CI 0.33-0.98), p = 0.0446]. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively [HR 0.90 (95% CI 0.68-1.18), p = 0.4560], while median ppOS was 20.2 months and 9.9 months, respectively [HR 0.73 (95% CI 0.52-1.03), p = 0.0748]. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs). CONCLUSION: Our study confirmed that in clinical practice, in case of "non-druggable" disease progression, maintaining osimertinib beyond progression (with adjunctive LATs) is an effective option.

Economic evaluation of sunitinib versus pazopanib and best supportive care for the treatment of metastatic renal cell carcinoma in Chile: cost-effectiveness analysis and a mixed treatment comparison.

Background: Sunitinib and Pazopanib are two metastatic renal cell carcinoma (MRCC) treatment alternatives, however the health system in Chile does not consider coverage for any. The cost-effectiveness versus relevant comparator was assessed to support evidence-based decision making. Methods: A four health states Markov model was built: first, second line treatments, BSC and death. Benefits were measured in QALYs, and efficacy estimates were obtained from an indirect treatment comparison. A 10-year time horizon and a 3% undifferentiated discount rate were considered. Deterministic and probabilistic sensitivity analyses were performed. Results: The costs of treating MRCC with Sunitinib were higher than Pazopanib and BSC. When comparing Sunitinib versus Pazopanib, the incremental benefit is small favoring Sunitinib (0.03 QALYs). The base case scenario shows an average ICER of PA versus BSC of US$62,327.11/QALY and of US$85,885/QALY for Sunitinib versus Pazopanib. The ICER was most sensitive to the OS relative to BSC, where evidence was associated to important bias. Conclusions: Sunitinib or Pazopanib can be considered cost-effective if a 3 GDP per-capita threshold is assumed. The decision between SU or PA is highly sensitive to the price of the drugs, rather than the outcomes. Therefore, the decision might be made based on cost-minimization exercise.

Estudio de impacto presupuestal de Daclatasvir asociado a Asunaprevir desde la perspectiva del sistema de salud público chileno.

OBJECTIVES: To assess the impact on the 2015 national health budget of incorporating Daclatasvir/Asunaprevir (DCV / ASV) for the treatment of Hepatitis C genotype 1b (HC1b) in Chile. METHODS: A Chilean HC1b patients cohort was modelled using local prevalence and incidence data. Two scenarios were built and compared, one were all patients receive Peginterferon/Ribavirin (PR) and another were all patients are treated with DCV/ASV. The analysis was conducted from the perspective of public health system of Chile assuming 100% reimbursement and a time horizon of 5 years. Costs associated with drug treatment, adverse events, other relevant resources and costs associated with disease complications were used. RESULTS: At a total DCV/ASV treatment price of USD $55,039, an additional of USD $65,6MM are required during the first year (prevalent cases) equivalent to 0.71% of the 2015 national health budget. From year 2 (incident cases), an additional of USD $12,3MM are needed (0.13% of the 2015 health budget). A price reduction of 33% (USD $36,693), requires an additional of USD $38,2MM the first year and USD $7,16MM from the second year (0.11% and 0.6% of the health budget). If the treatment price is reduced further (USD $18,347), an additional USD $10,9MM are required for the first year and USD $2,03MM from the second year (0.3% and 0.057% of the 2015 heath budget). CONCLUSION: The impact on the health budget ranges between 0.3% and 0.71% the first year and decreases to less than 0.15% from the second year considering the price assessed price range.

Anal human papillomavirus in HIV-uninfected men who have sex with men: incidence and clearance rates, duration of infection, and risk factors.

Little is known regarding the natural history of anal human papillomavirus (HPV) infection. We aimed to evaluate incidence and clearance rates, their risk factors, and duration of anal HPV infection in HIV-uninfected men who have sex with men (MSM). A longitudinal study was conducted. Anal samples were analysed using the Linear Array HPV Genotyping test. Incidence and clearance rates, and corresponding risk factors, were estimated using a two-state Markov model. Overall, 155 MSM (median age 33.4 years) attending the largest sexually transmitted infection (STI) centre in Rome, Italy, were followed for a median of 12.2 months (Q1-Q3: 7.0-18.1). Incidence and clearance rates for any HPV were 85.6 (95% CI: 58.4-125.4) and 35.6 (95% CI: 24.7-51.5) × 1000 person-months, respectively; the median duration of infection was 9.4 months (Q1-Q3: 7.5-12.1). Receptive anal sex emerged as the only risk factor for the acquisition of any HPV (Hazard Ratio, HR = 2.65, 95% CI: 1.16-6.06). The incidence rates for carcinogenic and non-carcinogenic types were 42.3 (95% CI: 29.2-61.4) and 29.2 (95% CI: 19.5-43.7) × 1000 person-months, respectively (p = 0.13); their clearance rates were 62.9 (95% CI: 45.1-87.7) and 65.7 (95% CI: 47.4-91.0) × 1000 person-months, respectively (p = 0.83). HPV16 showed the lowest clearance rate among carcinogenic types (59.7 × 1000 person-months), and a duration of infection of 16.8 months. In conclusion, a higher incidence rate was observed for carcinogenic compared to non-carcinogenic HPV types, although the difference was not significant. HPV16 emerged as the type with the longest duration of infection and the lowest clearance rate among carcinogenic types.

Posterior Reversible Encephalopathy Syndrome in late postpartum eclampsia.

Posterior Reversible Encephalopathy Syndrome (PRES) is a neurological complication associated with several medical conditions and it has been described in clinical findings of seizures, headache, vomiting, altered mental status, and visual changes and focal neurologic deficit, in conjunction with radiological findings of primarily posterior cerebral white matter edema of both cerebral hemispheres. PRES can develop in a wide array situations including pregnancy and postpartum in patients with or without symptoms and signs of eclampsia. A prompt diagnosis of PRES by magnetic resonance imaging and an immediate antihypertensive and anticonvulsant therapy can help to prevent serious complications. The clinical case presented deals with a 35 year-old pregnant woman whose history of eclampsia was observed after a cesarean section.

Predicting depression from illness severity in cardiovascular disease patients: self-efficacy beliefs, illness perception, and perceived social support as mediators.

BACKGROUND: Many studies have investigated the relationships between cardiovascular diseases and patients' depression; nevertheless, few is still known as regard the impact of illness severity on depression and whether psychosocial variables mediate this association. PURPOSE: The aim of this study is to investigate the putative mediating role of illness representations, self-efficacy beliefs, and perceived social support on the relationship between illness severity and depression. METHODS: A total of 75 consecutive patients with cardiovascular disease (80 % men; mean age = 65.44, SD = 10.20) were enrolled in an Italian hospital. Illness severity was measured in terms of left ventricular ejection fraction, whereas psychological factors were assessed using self-report questionnaires. RESULTS: The relationship between left ventricular ejection fraction and depression was mediated by identity illness perception, self-efficacy beliefs in managing cardiac risk factors, and perceived social support. CONCLUSION: The treatment of depression in cardiovascular disease patients may therefore benefit from a psychological intervention focused on patients' illness representations, self-efficacy beliefs, and their perceived social support.

Pacientes adultos com leucemia aguda - experiência da Faculdade de Medicina do ABC / Adult patients with acute leukemia - ABC Medical School experience

Introdução: Houve uma melhora lenta, porém definitiva no tratamento das leucemias agudas nos últimos anos. No entanto, existem controvérsias para pacientes com características específicas. Este trabalho tem como objetivo descrever o perfil epidemiológico dos pacientes com leucemia aguda atendidos no Hospital Estadual Mário Covas (HEMC), assim como demonstrar as curvas de sobrevida global e livre de doença e as taxas de mortalidade desta população. Métodos: Realizado estudo de corte transversal para avaliação de pacientes com diagnóstico de leucemias agudas da FMABC atendidos, no HEMC, no período de 2008 a 2012. Análise estatística das curvas de sobrevida utilizando Kaplan-Meier (XL Stat® v2012). Resultados: LMA: 50 pacientes com média de 57,72 anos de idade (18 a 89 anos), predomínio do sexo feminino 2,12: 1 e SLD = SG = 42 meses (média de seguimento = 49,9 meses); sendo 12 pacientes com LMA-M3 (SG=SLD=50%) e 38 outros subtipos (SG=SLD=39,5%). LLA: 17 pacientes, com média de 33,7 anos de idade (19 a 66 anos), predomínio do sexo masculino 1,43: 1 e SG = 58,82%, SLD = 47,3% (média de seguimento = 24,6 meses). Conclusão: Pacientes com LMA que atingem resposta na fase de indução apresentam curvas de SG e SLD compatíveis com a literatura. Pacientes com LLA apresentam SG e SLD inferior ao observado na literatura. É preciso prosseguir com este programa a fim de determinar o melhor tratamento para estes pacientes e o impacto do TCTH, assim como sua viabilidade.

Bisphosphonate therapy in patients under androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis.

The objective of this study was to clarify the role of bisphosphonates in the treatment of osteoporosis in patients with prostate adenocarcinoma under androgen deprivation therapy (ADT). The Medline, EMBASE, Cancerlit and the American Society of Clinical Oncology abstract databases were searched for published randomized, placebo-controlled trials evaluating the usage of bisphosphonates in patients with prostate cancer (PC) under ADT. The outcomes assessed were fracture, osteoporosis, incidence of adverse events and changes in bone mineral density (BMD) during treatment. A total of 15 articles (2634 participants) were included in the meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing fractures (risk ratio (RR), 0.80; P = 0.005) and osteoporosis (RR, 0.39; P <0.00001). Zoledronic acid showed the best number needed to treat (NTT), compared with placebo, in relation to fractures and osteoporosis (NNT = 14.9 and NNT = 2.68, respectively). The between-group difference (bisphosphonates vs placebo) in the lumbar spine and femoral neck BMD were 5.18 ± 3.38% and 2.35 ± 1.16%, respectively. This benefit of bone loss prevention could be reached without major side effects (cardiovascular or gastrointestinal events). Bisphosphonates are effective in preventing bone loss in patients with PC who are under ADT.

Physician, patient and family attitudes regarding information on prognosis: a Brazilian survey.

BACKGROUND: Communication between physicians and patients is a fundamental aspect of cancer care, yet most physicians' perceptions are often inconsistent with the patients' stated preferences while prognostic information is the most misunderstood. PATIENTS AND METHODS: Members of the Brazilian Society of Oncology Physicians (n=609) were identified and asked to complete a mailed questionnaire. Outpatients (n=150) and their family members (n=150), oncologists and fellows (n=55) from a public healthcare hospital and a tertiary cancer hospital in Sao Paulo were also personally invited to participate. RESULTS: A total of 202 physicians, 150 outpatients and 150 family members were participated. The majority of patients (92%) believe they should know about their terminal stage compared with 79.2% of physicians and 74.7% of families (P=0.0003). Cancer patients were most likely to support disclosure of diagnosis and terminality (P=0.001), to consider that this disclosure was not stressful (P<0.0001) and that this knowledge would improve their quality of life (P<0.0001). CONCLUSIONS: Cancer patients seen in these centers in Southeastern Brazil prefer to know the truth about their poor prognosis more than their physicians and families think. Further studies with larger samples of patients and physicians are necessary to show if our results are representative of all Brazilian situations.

Terapia de privación de andrógenos y obesidad mórbida: ¿tienen en común el riesgo cardiovascular por síndrome metabólico? / Androgen Deprivation Therapy And Morbid Obesity: Do They Share Cardiovascular Risk Through Metabolic Syndrome?

Antecedentes: A pesar de que el uso de la terapia de privación de andrógenos (TPA) ha producido una mejora en la supervivencia de hombres con cáncer de próstata avanzado, el hipogonadismo resultante se asocia con efectos negativos acusados, comparables a los que se observan en la obesidad mórbida, estando el riesgo cardiovascular entre los más letales. Objetivos: Evaluar el síndrome metabólico, las anomalías metabólicas y el riesgo cardiovascular en pacientes con cáncer de próstata sometidos a TPA, sin TPA y con obesidad mórbida. Métodos: Se trata de un estudio transversal que incluye a 79 hombres con cáncer de próstata, de los cuales 54 están sometidos a TPA y en 25 está ausente esta terapia, incluyéndose también a 91 pacientes con obesidad mórbida agrupados por sexo y edad. Para definir el síndrome metabólico empleamos los criterios de la Federación Internacional de Diabetes (FID). Se compararonl as anomalías metabólicas, los marcadores metabólicos y la puntuación Framingham entre los pacientes en terapia TPA, sin terapia TPA y con obesidad mórbida con el fin de predecir el riesgo de enfermedad coronaria a 10 años. Resultados: Los pacientes en terapia TPA presentaron una incidencia mucho mayor de diabetes y obesidad centralizada, así como mayores niveles de colesterol total y lipoproteínas de baja densidad (LBD), en comparación con los varones eugonadales. El riesgo cardiovascular medio fue significativamente superior en pacientes sometidos a TPA (39,97±12,53% vs. 26,09±14,80%; p = 0,021). Los sujetos con obesidad mórbida tenían un mayor riesgo de enfermedad coronaria a 10 años, comparable a la de los pacientes sometidos a TPA (p = 0,054). Conclusión: Este estudio apunta a que en los pacientes sometidos a TPA la preponderancia de anomalías metabólicas y riesgos cardiovasculares es mayor, siendo similar a la observada en sujetos con obesidad mórbida. Es posible que ambos procesos tengan en común el riesgo cardiovascular por vía de síndrome metabólico (AU)

Background: Although the use of androgen deprivation therapy (ADT) has resulted in improved survival in men with advanced prostate cancer, the resulting hypogonadism is associated with profound adverse effects comparable to those found in morbid obesity, being cardiovascular risk among the most lethal. Objectives: Evaluate metabolic syndrome, metabolic abnormalities and cardiovascular risk in patients with prostate cancer under ADT, not under ADT and morbid obese men. Methods: This is a cross-sectional study that involves 79 men presenting prostate cancer, of whom 54 under ADT and 25 not under ADT and 91 morbidly obese patients paired by sex and age. To define metabolic syndrome, we used the International Diabetes Federation (IDF) criteria. Metabolic abnormalities, metabolic markers and Framingham score to predict the ten year coronary heart disease risk were compared among patients under ADT, not under ADT and morbid obese. Results: Patients under ADT presented significantly greater occurrence of diabetes and central obesity and higher levels of total cholesterol and low density lipoprotein (LDL) compared to eugonadal men. The mean cardiovascular risk was significantly higher in patients under ADT (39.97±12.53% vs. 26.09±14.80%; p = 0.021). Morbidly obese subjects had increased ten year coronary heart disease risk; comparable to patients under ADT (p = 0.054). Conclusion: This study suggests that patients under ADT show higher prevalence of metabolic abnormalities and cardiovascular risk similar to those found in morbidly obese subjects. It is possible that both processes share cardiovascular risk through metabolic syndrome (AU)

[Androgen deprivation therapy and morbid obesity: do they share cardiovascular risk through metabolic syndrome?]. / Terapia de privación de andrógenos y obesidad mórbida: ¿tienenen común el riesgo cardiovascular por síndrome metabólico?

BACKGROUND: Although the use of androgen deprivation therapy (ADT) has resulted in improved survival in men with advanced prostate cancer, the resulting hypogonadism is associated with profound adverse effects comparable to those found in morbid obesity, being cardiovascular risk among the most lethal. OBJECTIVES: Evaluate metabolic syndrome, metabolic abnormalities and cardiovascular risk in patients with prostate cancer under ADT, not under ADT and morbid obese men. METHODS: This is a cross-sectional study that involves 79 men presenting prostate cancer, of whom 54 under ADT and 25 not under ADT and 91 morbidly obese patients paired by sex and age. To define metabolic syndrome, we used the International Diabetes Federation (IDF) criteria. Metabolic abnormalities, metabolic markers and Framingham score to predict the ten year coronary heart disease risk were compared among patients under ADT, not under ADT and morbid obese. RESULTS: Patients under ADT presented significantly greater occurrence of diabetes and central obesity and higher levels of total cholesterol and low density lipoprotein (LDL) compared to eugonadal men. The mean cardiovascular risk was significantly higher in patients under ADT (39.97±12.53% vs. 26.09±14.80%; p=0.021). Morbidly obese subjects had increased ten year coronary heart disease risk; comparable to patients under ADT (p=0.054). CONCLUSION: This study suggests that patients under ADT show higher prevalence of metabolic abnormalities and cardiovascular risk similar to those found in morbidly obese subjects. It is possible that both processes share cardiovascular risk through metabolic syndrome.

Cancer-related fatigue: a practical review.

Fatigue is an exceedingly common often treatable problem in cancer patients that profoundly affects all aspects of quality of life. Prevalence estimates have ranged from 50% to 90% of cancer patients overall. After addressing reversible or treatable contributing factors, such as hypothyroidism, anemia, sleep disturbance, pain, emotional distress, climacterium, medication adverse events, metabolic disturbances, or organ dysfunction such as heart failure, myopathy, and pulmonary fibrosis, patients may be screened with a brief fatigue self-assessment tool. All cancer patients should be screened regularly for fatigue. Those with moderate or severe fatigue may benefit from both pharmacologic and nonpharmacologic interventions, while mild fatigue that does not interfere with quality of life can be treated with nonpharmacologic measures alone. Physicians often have insufficient knowledge about fatigue and its treatments or underestimate the impact of fatigue on quality of life, while patients may consider it an unavoidable and untreatable side-effect and fear that reporting it may incite a change toward less aggressive cancer treatment. A practical review may therefore be useful to health care professionals in order to avoid the common barriers to its treatment that exist on the sides of both physicians and patients.

Doctor, how long?

This study aimed to quantify the average survival time of cancer patients once terminal sedation was started until death and identify potential variables that may influence their survival time on sedation. This is a retrospective cohort analysis of all consecutive terminal cancer patients who died after starting terminal sedation at public tertiary Brazilian Hospital. A total of 532 cancer patients died in Hospital Estadual Mário Covas during this period and 181 out of them who received terminal sedation were included in this analysis. The median survival was 27 h. By multivariate analysis, increase in the dose of sedative drug during sedation (odds ratio 1.576, 95% CI 1.113-2.232), use of opioids alone for sedation (odds ratio 1.438, 95% CI 1.046-1.977) and dyspnoea as cause of sedation (odds ratio 1.564 95% CI 1.045-2.341) were independent risk factors for a shorter survival time after starting terminal sedation. Sedated, terminal cancer patients usually live about 1 day. We identified risk factors for a shorter sedation period. This study is limited by its retrospective design and by the frequent use of opioids as the main sedative medications. Prospective studies must be carried out in order to validate these data.

Drug interactions in oncology: how common are they?

BACKGROUND: Drug-drug interactions (DDIs) comprise an important problem in medical oncology practice. We systematically reviewed the frequency of DDIs in oncology. METHODS: We searched PubMed for eligible articles and on-line databases for abstracts of major oncology meetings. RESULTS: Eight studies reported on the frequency of DDIs: six evaluated the frequency of potential DDIs, while two studies reported on real DDIs, i.e. interactions that had clinical consequences. Studies of potential DDIs found that approximately one-third of patients are exposed to dangerous drug doublets, with the most common ones involving warfarin and anticonvulsants. One study of real DDIs found that 2% of hospitalized cancer patients had a DDI as the cause of admission. CONCLUSIONS: Drug interactions comprise an important issue in oncology, with approximately one-third of ambulatory cancer patients being at risk of DDIs. Data are limited on the clinical consequences of drug interactions among cancer patients.

XM02, the first granulocyte colony-stimulating factor biosimilar, is safe and effective in reducing the duration of severe neutropenia and incidence of febrile neutropenia in patients with non-Hodgkin lymphoma receiving chemotherapy.

Recombinant granulocyte colony-stimulating factors (G-CSFs) such as filgrastim or lenograstim are being used to treat chemotherapy-induced neutropenia. The aim of the present study was to investigate a new G-CSF, XM02, in comparison to filgrastim in terms of safety and efficacy in the prevention of chemotherapy-induced neutropenia in non-Hodgkin-lymphoma (NHL). A total of 92 patients receiving chemotherapy were randomised in cycle 1 to treatment with daily injections (subcutaneous 5 microg/kg/day) of XM02 (n = 63) or filgrastim (n = 29) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received XM02. The mean duration of severe neutropenia (DSN) was 0.5 and 0.9 days in cycle 1 for XM02 and filgrastim, respectively (p = 0.1055). In cycle 1, the incidence of febrile neutropenia (FN) was 11.1% for XM02 and 20.7% for filgrastim (p = 0.1232). The adverse event profile was similar between XM02 and filgrastim. XM02 demonstrated equivalent efficacy and similar safety profile as the reference medication filgrastim. Treatment with XM02 is as beneficial as filgrastim in ameliorating severe neutropenia and FN in patients with NHL receiving chemotherapy. XM02 is safe and well tolerated in the doses applied in this study.

XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy.

BACKGROUND: Recombinant granulocyte colony-stimulating factors (G-CSFs) such as Filgrastim are used to treat chemotherapy-induced neutropenia. We investigated a new G-CSF, XM02, and compared it to Neupogen after myelotoxic chemotherapy in breast cancer (BC) patients. METHODS: A total of 348 patients with BC receiving docetaxel/doxorubicin chemotherapy were randomised to treatment with daily injections (subcutaneous 5 microg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of XM02 (n = 140), Neupogen (n = 136) or placebo (n = 72). The primary endpoint was the duration of severe neutropenia (DSN) in cycle 1. RESULTS: The mean DSN in cycle 1 was 1.1, 1.1, and 3.9 days in the XM02, Neupogen, and placebo group, respectively. Superiority of XM02 over placebo and equivalence of XM02 with Neupogen could be demonstrated. Toxicities were similar between XM02 and Neupogen. CONCLUSION: XM02 was superior to placebo and equivalent to Neupogen in reducing DSN after myelotoxic chemotherapy.