PAC1 Receptor Mediates Electroacupuncture-Induced Neuro and Immune Protection During Cisplatin Chemotherapy.

Platinum-based chemotherapy is an effective treatment used in multiple tumor treatments, but produces severe side effects including neurotoxicity, anemia, and immunosuppression, which limits its anti-tumor efficacy and increases the risk of infections. Electroacupuncture (EA) is often used to ameliorate these side effects, but its mechanism is unknown. Here, we report that EA on ST36 and SP6 prevents cisplatin-induced neurotoxicity and immunosuppression. EA induces neuroprotection, prevents pain-related neurotoxicity, preserves bone marrow (BM) hematopoiesis, and peripheral levels of leukocytes. EA activates sympathetic BM terminals to release pituitary adenylate cyclase activating polypeptide (PACAP). PACAP-receptor PAC1-antagonists abrogate the effects of EA, whereas PAC1-agonists mimic EA, prevent neurotoxicity, immunosuppression, and preserve BM hematopoiesis during cisplatin chemotherapy. Our results indicate that PAC1-agonists may provide therapeutic advantages during chemotherapy to treat patients with advanced neurotoxicity or neuropathies limiting EA efficacy.

Optimization of dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin against methicillin-resistant Staphylococcus aureus in neutropenic patients with cancer by Monte Carlo simulations.

The objective of this study was to evaluate the efficacy of various dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin against methicillin-resistant Staphylococcus aureus (MRSA) in neutropenic patients with cancer. Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to determine cumulative fraction of response (CFRs) in terms of area under the concentration-time curve/minimum inhibition concentration target. Currently clinical standard dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin were insufficient to provide expected CFRs against MRSA for neutropenic patients with cancer. The high dosing regimens of vancomycin (3500 mg/d), teicoplanin (800 mg/d) and daptomycin (8 mg/kg/d) could provide CFRs of ≥ 80%, showing a higher treatment success. However, the majority of CFRs with linezolid simulated dosing regimens reached < 80% against MRSA. Therefore, a strategy of high dosages of vancomycin, teicoplanin and daptomycin may be needed to attain optimal therapeutic efficacy against MRSA in neutropenic patients with cancer.

Prophylactic pegfilgrastim to prevent febrile neutropenia among patients receiving biweekly (Q2W) chemotherapy regimens: a systematic review of efficacy, effectiveness and safety.

BACKGROUND: Pegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is commonly used to prevent febrile neutropenia (FN), a potentially life-threatening complication, following myelosuppressive chemotherapy. The FDA label for pegfilgrastim specifies that it should not be administered 14 days before or within 24 h of administration of myelosuppressive chemotherapy, precluding the use of pegfilgrastim in biweekly (Q2W) regimens. The National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer guidelines support the use of prophylactic pegfilgrastim in patients receiving Q2W regimens. The objective of this study was to systematically review evidence from randomized clinical trials (RCTs) and observational studies that describe the effectiveness and safety of prophylactic pegfilgrastim in preventing FN among patients receiving Q2W regimens. METHODS: An Ovid MEDLINE, Embase, and Cochrane Library literature search was conducted to evaluate the evidence regarding efficacy, effectiveness, and safety of prophylactic pegfilgrastim versus no prophylactic pegfilgrastim or prophylaxis with other G-CSF in patients who were receiving Q2W chemotherapy regimens with high (> 20%) or intermediate (10-20%) risk of FN for a non-myeloid malignancy. Studies that addressed absolute or relative risk of FN, grade 1-4 neutropenia, all-cause or any hospitalization, dose delays or dose reductions, adverse events, or mortality were included. Studies where the comparator was a Q3W chemotherapy regimen with primary prophylactic pegfilgrastim were also included. RESULTS: The initial literature search identified 2258 publications. Thirteen publications met the eligibility criteria, including eight retrospective, one prospective, one phase 1 dose escalation study, and three RCTs. In nine of the 13 studies reporting incidence of FN, and in seven of the nine studies reporting incidence of neutropenia, administration of prophylactic pegfilgrastim in patients receiving Q2W regimens resulted in decreased or comparable rates of FN or neutropenia compared with patients receiving filgrastim, no G-CSF, lipefilgrastim or pegfilgrastim in Q3W regimens. In six of the nine studies reporting safety data, lower or comparable safety profiles were observed between pegfilgrastim and comparators. CONCLUSIONS: In a variety of non-myeloid malignancies, administration of prophylactic pegfilgrastim was efficacious in reducing the risk of FN in patients receiving high- or intermediate-risk Q2W regimens, with an acceptable safety profile. TRIAL REGISTRATION: PROSPERO registration no: CRD42019155572 .

Zinc deficits, mucositis, and mucosal macrophage perturbation: is there a relationship?

PURPOSE OF REVIEW: Mucositis is a common and therapy-limiting adverse effect of cancer treatments including radiotherapy, chemotherapy, and immunotherapy. The optimal zinc formulation, dosage, and timing of administration warrant further research as does the efficacious prevention of febrile mucositis that predisposes to febrile neutropenia. RECENT FINDINGS: Metaanalyses concluded that zinc sulfate failed to significantly reduce the incidence or severity of chemotherapy-induced oral mucositis, whereas polaprezinc was associated with a significant reduction. Three new trials were published in 2018. The first trial found that zinc sulfate reduced the incidence and severity of chemotherapy-induced oral mucositis. The second reported that polaprezinc reduced oral mucositis in pediatric patients receiving high-dose chemotherapy for hematopoietic stem cell transplantation. The third trial demonstrated efficacy for a zinc lozenge for postoperative sore throat induced by an endotracheal intubation. SUMMARY: Zinc deficits, dietary or induced by cancer, are common in patients with cancer. Febrile mucositis may better describe the condition linking mucositis with febrile neutropenia. Febrile mucositis disrupts treatment and may be life-threatening. A paradigm shift is needed for a more comprehensive understanding of febrile mucositis. Zinc effects on the thymic immunological network and T lymphocytes during chemoradiotherapy regimens also warrant further investigation.

Effectiveness and safety of the pre-prescription of garenoxacin in comparison to moxifloxacin for low-risk febrile neutropenia in breast cancer patients undergoing adjuvant and neoadjuvant chemotherapy.

PURPOSE: The purpose of this study was to compare the efficacy of the pre-prescription of garenoxacin mesylate hydrate (GRNX) with that of moxifloxacin hydrochloride (MFLX) in the management of breast cancer patients with low-risk febrile neutropenia. METHODS: Data from female patients who had been instructed to take previously prescribed oral GRNX or MFLX for 3 days during adjuvant and neoadjuvant chemotherapy if their body temperature exceeded 38 °C were analyzed. This study compared the effectiveness between these fluoroquinolones using a propensity score matching analysis. RESULTS: The 330 patients received 1192 administrations of chemotherapy between May 2007 and April 2014 and 136 (41.2%) patients had a total of 212 (17.8%) febrile episodes. The frequencies of febrile episodes were 19.5% (113/579) and 16.2% (99/613) in the GRNX and MFLX groups, respectively. After propensity score matching, 384 episodes were matched in each group. Febrile events occurred in 80 and 56 cases in the GRNX and MFLX groups, respectively. Treatment success was identified in 80.0% (64/80) of cases in the GRNX group and 64.3% (36/56) of cases in the MFLX group (P = 0.0494). Additionally, the therapeutic use of granulocyte-colony stimulating factor was 6.3% (5/80) of cases in the GRNX group and 17.9% (10/56) of cases in the MFLX group (P = 0.0498). There were few differences in the frequency of adverse effects between the two groups. CONCLUSIONS: These results indicate that the pre-prescription of GRNX may be a more effective option for the management of low-risk febrile neutropenia during adjuvant and neoadjuvant chemotherapy for breast cancer.

G-CSF guideline adherence in Germany, an update with a retrospective and representative sample survey.

BACKGROUND: Current guidelines (GL) recommend neutropenia prophylaxis with G-CSF after chemotherapy (CTX) for patients with high (≥ 20%), or, if additional risk factors are present, intermediate (≥ 10-20%) risk of febrile neutropenia. The first sample survey in 2012 (NP1) showed lack of GL adherence. The aim of this second sample survey was to evaluate if GL adherence and implementation have improved. METHODS: The sample size represented 1.0% of the incidences of lung and 1.1% of breast cancer in Germany in 2010. Data of patients with a febrile neutropenia (FN) risk ≥ 10% who had received at least 2 cycles of chemotherapy between October 2014 and September 2015 was surveyed retrospectively. RESULTS: Data from 573 lung cancer (LC) and 801 breast cancer (BC) patients was collected from 109 hospitals and 83 oncology practices with 222 physicians participating. Compared with the NP1 survey, GL adherence increased in LC and FN high-risk (HR) chemotherapy from 15.4 to 47.8% (p < 0.001), and in FN intermediate-risk (IR) chemotherapy from 38.8 to 44.3% (p = 0.003). In BC and FN-HR chemotherapy, GL adherence was unchanged: 85.6% vs. 85.1% (p = 0.73) but increased in FN-IR from 49.3 to 57.8% (p < 0.001). In all IR CTX cycles, there are also no significant differences in GL adherence between the first (51.3%) and subsequent cycles (51.1%; p = 0.948). In LC patients treated in certified or comprehensive cancer centers, the GL adherence in FN-HR chemotherapy was 53.0% vs. 44.9% in other centers (p = 0.295); in FN-IR chemotherapy, it was 45.1% vs. 43.8% (p = 0.750). In BC with FN-HR chemotherapy, GL adherence in certified or comprehensive centers was 85.4% vs. 84.7% in other institutions (p = 0.869); in FN-IR chemotherapy, it was 60.2% vs. 55.0% (p = 0.139). GL adherence in FN-HR chemotherapy and in FN-IR chemotherapy differed between pulmonologists and hematologist-oncologists (FN-HR: 25.0% vs. 43.6%, p < 0.001; 38.1% vs. 48.6%, p < 0.001). Comparing gynecologists with hematologist-oncologists, GL adherence in FN-HR chemotherapy was 86.2% vs. 82.5%. In FN-IR chemotherapy, GL adherence by gynecologists and hematologist-oncologists was 58.6% and 55.6%, respectively (p = 0.288; p = 0.424). Classification and regression tree analysis split pulmonologists and other specialists, with the latter adhering more to GL (p < 0.001). Hematologist-oncologists and gynecologists with more than 2 years of professional training in medical cancer therapy adhered more closely to GL than others (68.7% vs. 46.2%, p < 0.001). Pulmonologists attending ≥ 2 national congresses annually adhered more to guidelines than other pulmonologists (44.8% vs. 24.3%, p < 0.001). CONCLUSIONS: Adherence to G-CSF GL in Germany has increased but is still insufficient. Certified and comprehensive cancer centers show a higher rate of GL implementation. In GL adherence, there is still a disparity between cancer types and between oncology treatment specialists.

Phase I trial of selenium plus chemotherapy in gynecologic cancers.

PURPOSE: Preclinical studies performed in our laboratory have shown that high-dose selenium inhibits the development of carboplatin drug resistance in an ovarian cancer mouse xenograft model. Based on these data, as well as the potential serious toxicities of supranutritional doses of selenium, a phase I trial of a combination of selenium/carboplatin/paclitaxel was designed to determine the maximum tolerated dose, safety, and effects of selenium on carboplatin pharmacokinetics in the treatment of chemo-naive women with gynecologic cancers. Correlative studies were performed to identify gene targets of selenium. METHODS: Chemo-naïve patients with gynecologic malignancy received selenious acid IV on day 1 followed by carboplatin IV and paclitaxel IV on day 3. A standard 3 + 3 dose-escalating design was used for addition of selenium to standard dose chemotherapy. Concentrations of selenium in plasma and carboplatin in plasma ultrafiltrate were analyzed. RESULTS: Forty-five patients were enrolled and 291 treatment cycles were administered. Selenium was administered as selenious acid to 9 cohorts of patients with selenium doses ranging from 50 µg to 5000 µg. Grade 3/4 toxicities included neutropenia (66.7%), febrile neutropenia (2.2%), pain (20.0%), infection (13.3%), neurologic (11.1%), and pulmonary adverse effects (11.1%). The maximum tolerated dose of selenium was not reached. Selenium had no effect on carboplatin pharmacokinetics. Correlative studies showed post-treatment downregulation of RAD51AP1, a protein involved in DNA repair, in both cancer cell lines and patient tumors. CONCLUSION: Overall, the addition of selenium to carboplatin/paclitaxel chemotherapy is safe and well tolerated, and does not alter carboplatin pharmacokinetics. A 5000 µg dose of elemental selenium as selenious acid is suggested as the dose to be evaluated in a phase II trial.

Utilidad de sarilumab en la terapia de la artritis reumatoide / Usefulness of sarilumab in the treatment of rheumatoid arthritis

En junio de 2017, la European Medicines Agency aprobó sarilumab para el tratamiento de la artritis reumatoide, un nuevo anticuerpo monoclonal (subtipo IgG1) totalmente humano, que impide la unión de la interleucina (IL) 6 a las formas soluble y unida a la membrana del receptor de la IL-6, e inhibe la señal a través de IL-6. Administrado cada 2 semanas en dosis de 200 mg (con una dosis de 150 mg cada 2 semanas para el tratamiento de anormalidades de laboratorio), tiene una afinidad por el receptor muy elevada y ha demostrado ser un fármaco eficaz y seguro en el tratamiento de la artritis reumatoide. Esta eficacia se ha demostrado en diferentes ensayos clínicos evaluados en distintos escenarios: falta de respuesta a metotrexato, intolerancia y/o fallo a antifactor de necrosis tumoral alfa y en pacientes con intolerancia a metotrexato. Su doble dosis, su doble dispositivo de administración, su mecanismo dual y su beneficio reconocido lo sitúan como una nueva alternativa potencial en el tratamiento de la artritis reumatoide

In June 2017, the EMA approved sarilumab for the treatment of rheumatoid arthritis, a new monoclonal (subtype IgG1) fully human antibody directed against the alpha subunit of the interleukin-6 receptor complex that inhibits the signal through IL-6. The drug is administered every other week at a dose of 200 mg (or a dose of 150 mg every two weeks if there are laboratory abnormalities), shows very high affinity for the receptor and has proven to be an effective and safe drug in the treatment of rheumatoid arthritis (RA). Its efficacy has been demonstrated in several clinical trials in a variety of scenarios (lack of response to MTX, intolerance and / or failure to anti-TNF). Due to its double dose, the availability of two different devices for its administration, and its dual signaling mode of action and recognised benefit, sarilumab is a new potential alternative in the treatment of RA

Implementation of a Pathway for the Treatment of Fever and Neutropenia in Pediatric Patients With Cancer.

Fever and neutropenia is an oncologic emergency. Time-to-antibiotics (TTA) refers to the amount of time from initial provider evaluation for fever and neutropenia to intravenous antibiotic administration. Research supports that rapid time-to-antibiotics (RTTA) is associated with improved patient outcomes. This quality improvement project evaluated the success of implementing an RTTA pathway in pediatric oncology patients with fever and neutropenia. The setting was an advanced practice nurse-managed pediatric ambulatory infusion center where patients with fever and neutropenia were often evaluated and treated. In order to improve TTA, a multidisciplinary pathway was implemented with a goal of TTA that was less than 60 minutes from initial provider evaluation. Implementation of the RTTA pathway included discussion of shared expectations with the pharmacy and education departments and discussion of shared expectations with the bedside nurses and advanced practice nurses staffing the unit. Additionally, a preliminary lab test was utilized. Success of the implementation was evaluated through 2 measures: TTA and nurses' knowledge of fever and neutropenia and the importance of RTTA. The aims of this project were to improve TTA as well as nurses' knowledge of fever and neutropenia and the importance of RTTA, and both these aims were successfully attained.

A therapeutic benefit of daptomycin against glycopeptide-resistant gram-positive cocci bloodstream infections under neutropenia.

Antibiotic-resistant infections remain to be a major issue for all over the world. Although appropriate diagnosis and rapid treatment initiation are crucially important particularly in immunocompromised patients, selection of antibiotics without identification of causative bacteria is often challenging. A 44-year-old woman with acute myeloid leukemia (AML) under myelosuppression suffered from teicoplanin-resistant gram-positive cocci bacteremia. Taking severe neutropenia due to chemotherapy and glycopeptide-resistance into account, teicoplanin was empirically substituted with daptomycin, which led to prompt defervescence. This microorganism later turned out to be Leuconostoc lactis (L. Lactis), and daptmycin was continued to use based on antimicrobial susceptibility tests. As a result, empiric use of daptomycin successfully controlled glycopeptide-resistant gram-positive cocci bacteremia under neutropenia. This is the first report of daptomycin treatment for L. lactis bacteremia in a patient with AML under neutropenia. Our findings suggest that daptomycin would be a suitable treatment option for glycopeptide-resistant gram-positive cocci bloodstream infections, especially in myelosuppressive patients.

Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis in chemotherapy-induced febrile neutropenia among breast cancer and Non-Hodgkin's lymphoma patients under Taiwan's national health insurance system.

RATIONALE, AIM AND OBJECTIVE: The beneficial effects of granulocyte colony-stimulating factor (G-CSF) prophylaxis on reducing the risk of chemotherapy-induced febrile neutropenia (CIFN) were well documented throughout the literature. However, existing data regarding its cost-effectiveness were conflicting. We estimated the cost-effectiveness of G-CSF prophylaxis in CIFN under Taiwan's National Health Insurance (NHI) system. METHODS: Data on clinical outcomes and direct medical costs were derived for 5179 newly diagnosed breast cancer and 629 non-Hodgkin's lymphoma (NHL) patients from the NHI claims database. Patients were further categorized into three subgroups as "primary-", "secondary-" and "no -" prophylaxis based on their patterns of G-CSF use. Generalized estimating equations were applied to estimate the impact of G-CSF use on the incidence of CIFN. The incremental cost-effectiveness ratios of primary and secondary prophylactic G-CSF use were calculated and sensitivity analyses were performed. RESULTS: Primary prophylaxis of G-CSF decreased the incidence of CIFN by 27% and 83%, while secondary prophylaxis by 34% and 22% in breast cancer and NHL patients, respectively. Compared with those with no prophylaxis, the incremental cost per CIFN reduced in primary prophylaxis is $931 and $52 among patients with breast cancer and NHL, respectively. In contrast, secondary prophylaxis is dominated by no prophylaxis and primary prophylaxis in both cancer patients. CONCLUSION: Primary but not secondary prophylactic use of G-CSF was cost-effective in CIFN in breast cancer and NHL patients under Taiwan's NHI system.

Avoidant conversations about death by clinicians cause delays in reporting of neutropenic sepsis: Grounded theory study.

BACKGROUND: Evidence suggests that patients delay reporting symptoms of neutropenic sepsis (NS) despite the risk to their life. This study aimed to elicit factors that contribute to delayed patient reporting of NS symptoms. METHODS: A constructivist grounded theory study used observations of chemotherapy consultations (13 h) and 31 in-depth interviews to explore beliefs, experiences, and behaviors related to NS. Participants included women with breast cancer, their carers (partners, family, or friends), and clinicians. An explanation for patient delays was developed through theoretical sampling of participants to explore emerging areas of interest and through constant comparison of data and their coding. This entailed iterative and concurrent data collection and analysis. Data were collected until saturation. RESULTS: All patients who developed NS-type symptoms delayed presenting to hospital (2.5 h-8 days), sometimes repeatedly. Moderators of delay included metastatic disease, bereavement, fatalism, religious beliefs, and quality of relationships with clinicians. There was an interplay of behaviors between clinicians, patients, and carers where they subconsciously conspired to underplay the seriousness and possibility of NS occurring. CONCLUSIONS: Findings have implications for health risk communication and development of holistic service models.

Rates of major complications during neoadjuvant and adjuvant chemotherapy for early breast cancer: An off study population.

OBJECTIVES: To determine the incidence and risk factors for thromboembolic events (TE) and febrile neutropenia (FN) in patients receiving systemic chemotherapy for early breast cancer (EBC). METHODS: 325 patients received FEC75, FEC100-T or ECaP for EBC in 2013. RESULTS: TE occurred in 7.4% and FN in 19.1% of patients. Risk factors for TE were: central venous catheter (p = 0.011). Risk factors for FN were: FEC100-T treatment versus FEC75 and ECaP (p ≤ 0.001); lower pre-treatment neutrophil count (p = 0.009) and poorer performance status (p = 0.012). Two patients died from treatment-related toxicities. CONCLUSION: In real-world experience, the majority of patients completed adequate treatment, despite significant complications.

Bleomycin induced flagellate erythema in a patient with thalamic mixed germ cell tumour: Report of a rare adverse effect.

Bleomycin induced flagellate dermatitis is an uncommon and unique adverse effect. With the declining use of bleomycin, this complication is becoming increasingly infrequent in day-to-day clinical practice. We herein describe a case of a 13year old male patient with left thalamic mixed germ cell tumour treated by multimodality approach, who developed flagellate erythema after two cycles of combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). This brief report highlights the importance of awareness and timely identification and management of this dermatological toxicity in patients undergoing bleomycin based combination chemotherapy.

Cuidados de enfermagem a pacientes onco-hematológicos submetidos a altas doses de quimioterapia: revisão integrativa / Nursing care provided to hematologic cancer patients receiving high-dose chemotherapy: an integrative review / Cuidados de enfermería a pacientes onco-hematológicos sometidos a altas dosis de quimioterapia: revisión integradora

Objetivo: avaliar a partir da literatura nacional e internacional os cuidados de enfermagem prestados aospacientes onco-hematológicos adultos internados submetidos a altas doses de quimioterapia. Método: revisãointegrativa conduzida em seis etapas, a fim de responder a pergunta norteadora: “Quais os cuidados deenfermagem prestados aos pacientes onco-hematológicos adultos internados submetidos a altas doses dequimioterapia seguida ou não de TCTH?” A estratégia de busca foi realizada utilizando a combinação dosdescritores: enfermagem, doenças hematológicas, transplante de medula óssea, transplante de células-troncohematopoéticas e neutropenia, na Cochrane/Central, Cinahl, Lilacs e Medline. A análise e síntese dos dadosforam descritivas segundo as categorias temáticas identificadas. Resultados: a amostra foi constituída por 13estudos primários divididos em três categorias temáticas: Atividade física e fadiga, Segurança do paciente eCuidados com mucosite. Conclusão: as evidências sintetizadas contribuem para o enfermeiro selecionar eimplementar estratégias que possam prevenir ou controlar as condições que sejam limitantes ao pacientedurante o tratamento.(AU)

Objective: to identify in the Brazilian and international literature nursing care provided to adult hematologic cancer patients receiving high-dose chemotherapy. Method: integrative review conducted in six stages intended to answer the question: "What type of nursing care is provided to adult hematologic cancer patients receiving high-dose chemotherapy followed by HSCT or not?" The search strategy included the combination of the descriptors: nursing, hematologic diseases, bone marrow transplantation, hematopoietic stem cell transplantation, and neutropenia in the Cochrane/Central, Cinahl, Lilacs and Medline databases. The analysis and synthesis of data were described according to thematic categories. Results: the sample was composed of 13 primary studies divided into three thematic categories: Physical exercises and fatigue, Patient safety, and Mucositis care. Conclusion: synthesized evidence enables nurses to select and implement strategies intended to prevent or control conditions that limit patients during treatment.(AU)

Objetivo: evaluar a partir de la literatura brasileña e internacional los cuidados de enfermería prestados a pacientes onco-hematológicos adultos internados sometidos a altas dosis de quimioterapia. Método: revisión integradora conducida en seis etapas para responder a la pregunta orientadora: "¿Cuáles los cuidados de enfermería prestados a los pacientes onco-hematológicos adultos internados sometidos a altas dosis de quimioterapia seguida o no de TCTH?" La estrategia de búsqueda fue aplicada utilizando la combinación de los descriptores: enfermería, enfermedades hematológicas, trasplante de médula ósea, trasplante de célulastronco hematopoyéticas y neutropenia, en la Cochrane/Central, Cinahl, Lilacs y Medline. El análisis y síntesis de los datos fueron descriptivos según las categorías temáticas identificadas. Resultados: la muestra abarcó 13 estudios primarios divididos en tres categorías temáticas: Actividad física y fatiga, Seguridad del paciente y Cuidados con mucositis. Conclusión: las evidencias sintetizadas contribuyen para que los enfermeros seleccionen e implementen estrategias capaces de prevenir o controlar las condiciones limitadoras al paciente durante el tratamiento.(AU)

FOLFOX chemotherapy can safely be given to neutropenic patients with early-stage colorectal cancer for higher dose intensity and fewer visits.

PURPOSE: How does giving adjuvant FOLFOX chemotherapy to patients with early-stage colorectal cancer (ESCRC) regardless of the day-before absolute neutrophil counts (ANC) effect chemotherapy-induced febrile neutropenia (CIFN) rates, received dose intensity (RDI), and chemotherapy cycle delay? Does an ANC level predict future neutropenia? METHODS: A retrospective chart review was conducted on all patients receiving adjuvant chemotherapy for ESCRC at a mid-sized community hospital in Toronto, Ontario, Canada between April 2005 and May 2014. All patients were under one medical oncologist. Day-before CBC data were collected along with other patient characteristics. CIFN was confirmed by hospital records. Inclusion criteria were met by 132 patients. Overall, 1074 cycles of chemotherapy were analyzed. RESULTS: Six episodes of CIFN were observed. There was a significant difference in the average day-before ANC between patients who developed CIFN (1.4 × 10(9)/L, 95 % CI 0.76-2.0 × 10(9)/L) and those who did not (2.9 × 10(9)/L, 95 % CI 2.8-3.0 × 10(9)/L, p = 0.03). The RDI for oxaliplatin was 0.95 and for 5-fluorouracil (5-FU) was 0.96. A total of 170 cycles were given at day-before ANC <1.5 × 10(9)/L (range 0.1 × 10(9)/L-1.4 × 10(9)/L), and 24 were delayed for 1 week for hematologic reasons. Cycles given with grade 2 neutropenia predicted higher grades of neutropenia with a sensitivity of 0.22 (95 % CI 0.12-0.38). CONCLUSIONS: Adjuvant FOLFOX chemotherapy may be given in the setting of low day-before ANC to patients with ESCRC. The benefits include higher RDI and a reduced number of clinic visits for the patient.

The prophylactic use of Chinese herbal medicine for chemotherapy-induced leucopenia in oncology patients: a systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: We performed a systematic review and meta-analysis to explore the clinical application of Chinese herbal medicine (CHM) for chemotherapy-induced leucopenia and to evaluate its effectiveness and safety. METHODS: We included randomized clinical trials (RCTs) with no limitation of publication type or language. Participants were cancer patients undergoing chemotherapy. Trial designs included comparisons of CHM with granulocyte colony-stimulating factor, supportive treatments for leucopenia, and/or placebo. Main outcomes were white blood cell count and incidence of leucopenia. Screening, data extraction, and analysis were conducted according to the PRISMA guidelines. RESULTS: Eighty-three RCTs (n = 8,012) met the inclusion criteria. Fifteen Chinese patent medicines and 47 different modified formulas were used as prophylaxis for chemotherapy-induced leucopenia. Compared with no treatment, CHMs were shown to decrease the incidence of leucopenia (odds ratio (OR) -0.23 [-0.20, -0.27]), P < 0.00001), with the number needed to treat (NNT) -3.45 [-3.13, -3.85]. Subgroup analysis suggested a prophylactic benefit for white blood cell counts with Fufang E-jiao Jiang, Diyu Shengbai Pian, combination Huangqi and Shengmai Zhusheye, and Fuzhong Shengbai Fang for patients undergoing chemotherapy. No serious adverse events were reported. Only three articles (3/83, 4 %) were rated as having adequate methodological quality with a low level of bias. Funnel plots were asymmetrical. CONCLUSIONS: Some CHMs may be efficacious in the treatment of chemotherapy-induced leucopenia, but the majority of reviewed studies were of poor quality. Results need to be confirmed in rigorously conducted high-quality trials, including pharmacokinetic studies to ensure that there are no interactions between the CHM agent and chemotherapy.

Incidence of febrile neutropenia in early stage breast cancer patients receiving adjuvant FEC-D treatment.

PURPOSE: The purpose of this study is to determine the incidence of febrile neutropenia (FN) among women receiving FEC-D (flurouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2) every 3 weeks for three cycles followed by docetaxel 100 mg/m(2) every 3 weeks for three cycles) chemotherapy for early stage breast cancer (ESBC) and the impact of primary granulocyte colony-stimulating factor (G-CSF) prophylaxis in a non-clinical trial setting. PATIENTS AND METHODS: A retrospective chart review of women referred for ESBC to The Moncton Hospital between 2005 and 2010 evaluated patient and disease characteristics, adjuvant chemotherapy receipt, G-CSF usage, FN incidence, hospital admission rates, and length of stay. Association of variables with FN was examined, and exploratory multivariable logistic regression modeling examined the impact of baseline variables on risk of FN. RESULTS: Of 520 patients enrolled in the database, 251 (48.3 %) received adjuvant chemotherapy for ESBC. Most (66.9 %) received FEC-D. Overall, 55 (21.9 %) patients developed FN. Forty-four (26.2 %) patients on FEC-D developed FN. Forty of 129 (31.0 %) FEC-D patients who did not receive primary G-CSF prophylaxis developed FN, versus 4 of 39 (10.3 %) receiving G-CSF. Receipt of FEC-D or TC (docetaxel 75 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks for four or six cycles) was associated with odds ratios of 6.5 or 6.77, respectively, for the development of FN. Receipt of trastuzumab with chemotherapy was associated with an odds ratio of 3.48 for developing FN versus no trastuzumab. Primary G-CSF prophylaxis led to a 63 % reduction in the odds ratio of developing FN. CONCLUSIONS: Incidence of FN with FEC-D treatment is considerably higher in clinical practice than reported in phase III trials. Consistent with ASCO guidelines, prophylactic G-CSF should be considered for all ESBC patients receiving adjuvant FEC-D.

Feasibility, efficacy, and adverse effects of outpatient antibacterial prophylaxis in children with acute myeloid leukemia.

BACKGROUND: Intensive chemotherapy for pediatric acute myeloid leukemia incurs the risk of infectious complications, but the benefits of antibiotic prophylaxis remain unclear. METHODS: In the current study, among 103 children treated on the AML02 protocol between October 2002 and October 2008 at St. Jude Children's Research Hospital, the authors retrospectively assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia, clinically or microbiologically confirmed infections (including bacteremia), and antibiotic resistance, as well as on the results of nasal and rectal surveillance cultures. Initially, patients received no prophylaxis or oral cephalosporin (group A). The protocol was then amended to administer intravenous cefepime alone or intravenous vancomycin plus either oral cephalosporin, oral ciprofloxacin, or intravenous cefepime (group B). RESULTS: There were 334 infectious episodes. Patients in group A had a significantly greater frequency of documented infections and bacteremia (both P < .0001) (including gram-positive and gram-negative bacteremia; P = .0003 and .001, respectively) compared with patients in group B, especially viridans streptococcal bacteremia (P = .001). The incidence of febrile neutropenia without documented infection was not found to be different between the 2 groups. Five cases of bacteremia with vancomycin-resistant enterococci (VRE) occurred in group B (vs none in group A), without related mortality. Two of these cases were preceded by positive VRE rectal surveillance cultures. CONCLUSIONS: Outpatient intravenous antibiotic prophylaxis is feasible in children with acute myeloid leukemia and reduces the frequency of documented infection but not of febrile neutropenia. Despite the emergence of VRE bacteremia, the benefits favor antibiotic prophylaxis. Creative approaches to shorten the duration of prophylaxis and thereby minimize resistance should be explored.