Fluconazole Treatment of Neonates and Infants with Severe Fungal Infections

1997 ◽  
Vol 25 (4) ◽  
pp. 214-218 ◽  
Author(s):  
AN Gürpinar ◽  
E Balkan ◽  
N Kiliç ◽  
İ Kiriştioǧlu ◽  
İ Avşar ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Clinical Response ◽  
Fungal Infections ◽  
Efficacy And Safety ◽  
Duration Of Therapy ◽  
Day Range ◽  
The Mean ◽  
Neonates And Infants

A total of 24 neonates and infants, aged from 2 days to 10 months, received treatment with intravenous fluconazole for microbiologically documented or presumed fungal infection. The mean fluconazole dosage was 6 mg/kg/day (range 2 –16 mg/kg/day) and the mean duration of therapy was 25 days (range 5–72 days). Efficacy was evaluated in neonates with proven fungal infections, as documented by the presence of pathogen at baseline. A positive clinical response was achieved in 23 of the 24 clinically evaluable patients (96%); eradication of the fungal organism was also achieved in 23 of the 24 evaluable patients (96%). Adverse events occurred in two patients (8%) but therapy was not discontinued in either patient. The present results confirm the efficacy and safety of fluconazole in the treatment of neonates and infants with severe fungal infections.

First Line Antifungal Treatment with Caspofungin of Oncohemopatic Patients. A Single Centre Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5271-5271 ◽  
Author(s):  
Alessandro Bonini ◽  
Alessia Tieghi ◽  
Luigi Gugliotta
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Ct Scan ◽  
Mechanism Of Action ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Antifungal Drugs ◽  
Severe Neutropenia ◽  
First Line ◽  
The Mean

Abstract Infections are the main complication for patients (pts) with hematologic diseases and severe neutropenia and among them fungal infections are the most difficult to treat and a major cause of mortality. The availability of a new class of antifungal drugs (echinocandins) could improve the chance of cure. Caspofungin (Caspo) is the first drug which is able to destroy the fungal cell wall. Since January 2004 we have treated 28 consecutive adult oncohemopatic and neutropenic pts with Caspo as first line therapy. In case of persistent fever (4 days) despite broad spectrum antibiotic therapy (association of Tazobactam/Piperacillin, Amikacin with or without Vancomycin) with negative blood cultures, a high-resolution CT-scan of the lungs, an abdomen US-scan, swabs from pharynx, nose and rectum, galactomannan test (this test is available at our Centre since February 2006) were performed. In the presence of any other sign or symptom we performed any other test according to the physicyan’s choice. In case of possible, probable or proven fungal infection (according to the EORTC criteria) Caspo was administered at the dosage of 70 mg i.v. on the first day followed by 50 mg i.v. in 1 hour daily. The pts were 15 males and 13 females; the mean age was 46 yrs (range 18–66 yrs). The diagnoses were: acute myeloid leukemia 13, acute lymphoblastic leukemia 5, multiple myeloma 2, lymphoma 8; the disease’s phases were: onset 9, complete remission 11, relapse 2, resistant 6. Six pts received an allogeneic and 4 an autologous BMT; the other pts received an induction or consolidation or rescue chemotherapy course. All the pts had severe neutropenia and the fungal infections were proven in 3 cases (2 aspergillus spp and 1 aspergillus fumigatus), probable in 3 cases and possible in 22 cases. The first site of infection was the lung in 27 pts and paranasal sinuses in 1 patient. CT scan was positive (halo sign, air-crescent sign or cavitation) in all the pts with a lung localization. The mean time of treatment was 18 days (range 6–21 days). The treatment was not discontinued for anyone because of adverse events and no modifications of the dosage were necessary. All the pts submitted to an allogeneic BMT received concomitant therapy with Cyclosporine A and we had not to change the dosage and we did not found any renal or liver alterations. No adverse events during the infusion of Caspo were seen and it was not necessary to administer any drug before the infusion as premedication. No breakthrough fungal infections were found. The infection was cured in 24/28 pts; 4 pts died for fungal infection progression (3 with a progression to the brain and in 1 case the infection remained in the lungs). For all the cured pts there was a concomitant recovery of neutrophils so also in our experience this appears to be a crucial fact for the resolution of the infection. Among the 24 cured patients 8 died later: 5 for hematologic disease and 3 for sepsis during malignant disease recurrence. In 2 cases there was the recurrence of the fungal infection despite the secondary prophylaxis with Caspo. In conclusion we can say we have a new treatment option for fungal infections in neutropenic pts with a new mechanism of action; this option seems safe, it does not preclude any other treatment (such as Cyclosporine), it is well tolerated and the resolution rate of the infections is very high, probably because of the new mechanism of action of the drug. Moreover the cost is lower than other antifungal treatments.

Antifungal Treatment with Caspofungin: A Single Centre Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5386-5386
Author(s):  
Alessandro Bonini ◽  
Alessia Tieghi ◽  
Luigi Gugliotta
Keyword(s):  
Adverse Events ◽  
Antibiotic Therapy ◽  
Fungal Infection ◽  
Broad Spectrum ◽  
Fungal Infections ◽  
The Other ◽  
Broad Spectrum Antibiotic ◽  
Persistent Fever ◽  
Neutropenic Patients ◽  
The Mean

Abstract Infections are the main complication for patients with hematologic diseases and severe neutropenia and among them fungal infections are the most diffucult to treat and a major cause of mortality for these patients. Now we have a new antifungal class, Echinocandins which work with a new and different mechanism of action regarding azoles and amphotericin B, so we wanted to verify the tolerability and efficacy of Caspofungin (Caspo). From January 2004 until now we have treated 15 consecutive oncohemopatic and neutropenic patients admitted at our Institution. The schedule of treatment was: in case of persistent fever (at least 4 days) during broad spectrum antibiotic therapy a high-resolution CT-scan of the lungs, an abdomen US-scan, swabs from pharynx, nose and rectum and blood cultures were performed. In case of positivity of one or more of these findings suggesting for invasive fungal disease, Caspofungin was administered at the dosage of 70 mg i.v. on the first day and 50 mg i.v. from the second day; the infusion time was 1 hour. The patients were 10 males and 5 females, the mean age was 46 yrs (range 19–60 yrs). The diagnoses were: acute myeloid leukemia 8, acute lymphoblastic leukemia 3, lymphoma 4; the disease’s phases were: onset 3, first remission 3, remission>I 2, partial remission 5, relapse 1, resistant 1. Two patients received an allogeneic BMT, 1 an autologous BMT, the other patients an induction or consolidation or rescue chemotherapy course. In four cases Caspo was administered as secondary prophylaxis of a previous invasive fungal infection while for the other patients Caspo was administered for persistent fever and at least one lesion of the lungs or other organs with no evidence of bacterial or viral infection. The mean time of treatment was 18 days (range 6–21 days); the treatment was not discontinued for anyone of them because of adverse events; the dosage of Caspo was not changed for anyone. For the 2 allogeneic BMT Cyclosporine A administration was not changed and we did not found any renal or liver alterations. All the patients received a concomitant broad spectrum antibiotic therapy (association of Tazobactam/Piperacilline, Amikacine and Vancomycin) and for none of them we registered any liver or renal disfunction. No adverse events during the infusion of Caspo were seen and it was not necessary to administer any drug before the infusion. We did not seen breakthrough fungal infections. In 2 patients a proven fungal infection (Aspergillus fumigatus and Aspergillus spp) was demonstrated so the other cases remained probable or possible infections. No progression of the infection was seen. All the infections, except one, resolved; one patient died after 6 days of antifungal treatment for leukemia progression. Five patients died: 4 for leukemia and 1 for bacterial infection (Pseudomonas aeruginosa) after the fungal infection. In conclusion now we have a new treatment option for fungal infections in neutropenic patients and this option is safe, it does not preclude any other treatment (such as CsA), it is well tolerated and the resolution rate of the infections is very high, probably because of the new mechanism of action of the drug. Moreover the cost of the drug is lower than other antifungal treatments. According to these preliminary data we have decided to continue this experience to verify them in a larger cohort of patients.

Micafungin Is Extremely Effective Against Fungal Infections Complicating Hematological Malignancies: Report of a Multicenter Study by N-FISH (Niigata Fungal Infection Study Group in Hematology).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5350-5350
Author(s):  
Sadao Aoki ◽  
Jun Takizawa ◽  
Yoshinobu Seki ◽  
Kazue Takai ◽  
Koji Nikkuni ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Multicenter Study ◽  
Liver Dysfunction ◽  
Hematological Malignancies ◽  
Fungal Infections ◽  
The United States ◽  
Study Group ◽  
The Mean ◽  
Infection Study

Abstract [Background]Micafungin (MCFG) is a candin antifungal agent, and was marketed in Dec. 2002 in Japan and in Apr. 2005 in the United States. The Niigata Fungal Infection Study Group in Hematology (N-FISH) performed a multicenter prospective study to clarify the therapeutic effects of MCFG on deep fungal infections complicating hematological malignancies. [Methods]A total of 36 pts. who had been treated in centers belonging to N-FISH between Oct. 2003 and Apr. 2005 were included in this study. They consisted of 14 men and 22 women with a mean age of 53.5 years: 14 pts. with AML, 10 pts. with malignant lymphoma, 6 pts. with ALL, and 6 pts with other diseases. They had a proven fungal infection, or were suspected of having a fungal infection because of fever unresponsive to antimicrobial agents or from laboratory data. Three of them had a proven infection, and 33 were suspected of having a fungal infection. Three of these 33 pts. failed to respond to fluconazole. As a rule, MCFG was administered for more than 14 days until infectious symptoms improved or disappeared. When MCFG was judged ineffective because of the worsening of clinical symptoms despite the administration of MCFG, or when the administration of MCFG was judged difficult because of adverse effects, the drug was discontinued or replaced by other drugs. Two pts. orally received amphotericin B syrup singly. [Results]The mean dose of MCFG was 2.6 mg/kg (1.5–4.2 mg/kg), and the mean duration of administration was 15.9 days (5–85 days). Complete or partial response was achieved in 31 (86.1%) of the 36 pts., who showed improvements in infectious symptoms. In 4 pts, MCFG was discontinued because of insufficient effects. There were no breakthrough fungal infections within 7 days after the completion of MCFG therapy. Of the 36 pts., 31 (86.1%) and 24 (66.7%) survived 1 and 3 months after MCFG therapy, respectively. The cause of death was exacerbation of the primary disease, and not exacerbation or the onset of a fungal infection. Eight adverse events occurred in 7 pts.: hypoglycemia in 1, liver dysfunction in 3, eosinophilia in 1, kidney dysfunction in 2, and hypokalemia in 1. In 1 of the 3 pts. with liver dysfunction (grade 3), MCFG therapy was discontinued, with rapid improvement of the liver dysfunction. All other adverse events were mild, allowing continued MCFG therapy. [Conclusion]This multicenter study demonstrated the effectiveness and safety of MCFG therapy for deep fungal infections complicating hematological malignancies. The results suggest that MCFG should be promptly used for fever associated with a fungal infection complicating hematological malignancies.

First Line Treatment of Probable and Proven Invasive Aspergillosis with Caspofungin in Oncohemopatic Patients. A Single Centre Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4836-4836
Author(s):  
Alessandro Bonini ◽  
Alessia Tieghi ◽  
Barbara Gamberi ◽  
Annalisa Imovilli ◽  
Cristiano Carbonelli ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Cyclosporin A ◽  
Ct Scan ◽  
Fungal Infections ◽  
Severe Neutropenia ◽  
Cell Transplant ◽  
First Line ◽  
Hematopoietic Stem ◽  
The Mean

Abstract Infections are the main complication for patients (pts) with hematologic diseases and severe neutropenia. In particular fungal infections are the most difficult to treat and represent a major cause of mortality. Caspofungin (Caspo) is the first drug which is able to inhibit the growth of the fungal cell wall. Since January 2004 we have treated 64 consecutive adult neutropenic pts with Caspo as first line therapy. In the setting of persistent fever (3 days) despite broad spectrum antibiotic therapy and negative blood cultures, a high-resolution CT-scan of the lungs, an abdomen US-scan, swabs from pharynx, nose and rectum, galactomannan test were performed. In the setting of probable or proven fungal infection (according to the revised EORTC criteria and Cornely CID 2007) Caspo was administered at the dose of 70 mg i.v. on the first day followed by 50 mg i.v. in 1 hour daily. They were 35 males and 29 females; the mean age was 56 yrs (range 19–77 yrs). The diagnoses were: acute leukemia 46 (72%), myeloma 2 (3%), lymphoma 14 (22%) and chronic leukemia 2 (3%); the disease’s phases were: new onset 26 (41%), remission 16 (24%), relapse 22 (35%). Thirteen pts received an allogeneic and 5 an autologous hematopoietic stem cell transplant; the other pts received an induction or consolidation or rescue chemotherapy course. Fungal infections were proven in 13 cases (20% including 11 aspergillus spp, 1 aspergillus fumigatus, 1 G. capitatum) and probable in 51 cases (80%). The first site of infection was the lung in 63 pts (98%) and paranasal sinuses in 1 patient (2%). CT scan was positive (halo sign or air-crescent sign) in all the pts with a lung localization, while the chest X-ray was positive in 40% of them. BAL was performed in 31 pts. The mean time of treatment was 18 days (range 13–25 days). Caspo was well tolerated and not discontinued for adverse events. Among pts submitted to an allogeneic HSCT the concomitant therapy with Cyclosporin A was not influenced by Caspo. No adverse events during the infusion of Caspo were seen, and it was not necessary to administer any drug before the infusion as premedication. The global (partial and complete) response was 55/64 (86%); 9 pts died for fungal infection. The efficacy responses were generally similar for probable and proven infections. No breakthrough fungal infections were found. All surviving patients, upon discharge from the hospital, received oral treatment with Voriconazole or Posaconazole. For all the cured pts, there was a concomitant recovery of neutrophils so also in our experience this appears to be a crucial factor for the resolution of the infection. Among the 55 responsive patients, 25 (45%) died later: 23 for hematologic disease and 2 for sepsis during recurrence of the malignant disease. In 2 cases there was the recurrence of the fungal infection. In conclusion the resolution rate of the infections is very high (86%); Caspo seems safe, it does not preclude any other treatment (such as Cyclosporin A), it is well tolerated and the cost is lower than other antifungal treatments.

A multicenter prospective hospital-based cohort study on the efficacy and safety of pitavastatin.

2020 ◽  
Vol 17 ◽  
Author(s):  
Abdullah Shehab ◽  
Asim Ahmed Elnour ◽  
Akshaya Srikanth Bhagavathula ◽  
Joseph Pulavelil Kurian ◽  
Gazi Hassan ◽  
...  
Keyword(s):  
Cohort Study ◽  
Adverse Events ◽  
United Arab Emirates ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Efficacy And Safety ◽  
Onset Diabetes ◽  
The Mean ◽  
New Onset

Aims: We aim to investigate the efficacy and safety of pitavastatin 4 mg in a population of people living in the United Arab Emirates (UAE). Background: Pitavastatin is a member of the HMG-CoA reductase inhibitors family which was approved for use in adult subjects with primary hyperlipidemia or mixed dyslipidemia. To date, no published studies have assessed the efficacy and safety of pitavastatin in the United Arab Emirates. Objective: The main objective of the current study was to investigate the efficacy and safety of pitavastatin in subjects with dyslipidemia for primary prevention of cardiovascular diseases based on total cardiovascular risk. Methods: This was a multicentre (four private hospitals) prospective cohort study to analyze data on the use of pitavastatin for dyslipidemia in adult outpatients in Abu Dhabi and Dubai emirates, United Arab Emirates. We have followed-up the clinical profiles of subjects in four hospitals for six-weeks during the period from June 2015 to June 2017. Efficacy was based on the evaluation of the mean (± standard deviation) change in low-density lipoprotein cholesterol between baseline and week six after the initiation of pitavastatin therapy. Safety was reported as the incidence of adverse events occurred with the use of pitavastatin and the development of new-onset diabetes. Results: A total of 400 subjects who were receiving pitavastatin 4 mg were included. The mean age of subjects was 50.7 ±10.8 years, of these 79.0% were males. At the baseline, the mean level of total cholesterol was 185.4 ±41.5 mg/dL, low density lipoprotein was 154.9 ±48.55 mg/dL, high-density lipoprotein cholesterol was 40.5 ±11.23 mg/dL and fasting blood glucose was 115.0 (±16.63) mg/dl. At the end of six weeks, low density lipoprotein levels significantly decreased to 112.09 ±41.90 mg/dl (standard mean difference [SMD] (-42.8%), 95% CI: -42.88 [-49.17 to -36.58] mg/dl, P <0.001), while high density lipoprotein levels improved (SMD, 95% CI: 1.77% [0.25 to 3.28] mg/dl, P <0.022). There were 55 subjects (13.7%) reported various adverse events such as myalgia (7.5%), sleep disorders (2.5%), and myopathy (2.2%). Furthermore, 4 (1.0%) have had developed new-onset diabetes post six-weeks of initiation of pitavastatin therapy. Conclusion: Pitavastatin 4 mg had howed robust efficacy in reducing LDL-C levels and improving HDL-C levels in subjects with dyslipidemias. The use of pitavastatin was associated with a low discontinuation rate, fewer adverse events, and very limited cases of new-onset diabetes.

Clinical efficacy and safety following dose tapering of ciclosporin in cats with hypersensitivity dermatitis

2016 ◽  
Vol 18 (11) ◽  
pp. 898-905 ◽  
Author(s):  
Elizabeth S Roberts ◽  
Tiffany Tapp ◽  
Ann Trimmer ◽  
Linda Roycroft ◽  
Stephen King
Keyword(s):  
Adverse Events ◽  
Clinical Response ◽  
Clinical Efficacy ◽  
Safety Profile ◽  
Therapeutic Response ◽  
Clinical Pathology ◽  
Efficacy And Safety ◽  
Dosing Frequency ◽  
Dosing Regimens ◽  
Physical Examinations

Objectives This study was designed to evaluate the efficacy and safety of reducing ciclosporin (CsA) dosing frequency from daily to every other day (EOD) or twice a week (TW) according to clinical response in cats with hypersensitivity dermatitis (HD) and treated with CsA. Methods One hundred and ninety-one cats with HD were given 7 mg/kg CsA daily for at least 4 weeks. Depending on clinical response, the dosing frequency was tapered from daily to EOD over the next 4 weeks and further to TW for an additional 4 weeks. Safety was evaluated through physical examinations, clinical pathology and the monitoring of adverse events (AEs). Results The majority of cats were able to have their dose of CsA tapered to either EOD (15.5%) or TW (62.9%) according to the clinical response. Observed AEs were most frequently mild and self-limiting vomiting and diarrhea. A higher percentage of AEs occurred with daily administration (73%) compared with other dosing regimens (27%). Conclusions and relevance Following 4 weeks of daily dosing at 7 mg/kg, CsA may be tapered to EOD or TW while maintaining the desired therapeutic response in cats with HD. Additionally, CsA appears to be well tolerated with fewer AEs at EOD or TW dosing. Establishing the lowest effective dosing frequency of CsA improves the drug’s safety profile.

Efficacy and Safety of Micafungin as An Empirical Antifungal Therapy for Suspected Fungal Infection in Patients with Hematological Disorders.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1939-1939
Author(s):  
Minoru Yoshida ◽  
Kazuo Tamura ◽  
Masahiro Imamura ◽  
Yoshiro Niitsu ◽  
Takeshi Sasaki ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Antifungal Therapy ◽  
Clinical Symptoms ◽  
Fungal Infections ◽  
Efficacy And Safety ◽  
Hematopoietic Stem ◽  
Persistent Fever ◽  
Hematological Disorders ◽  
Study Results ◽  
Empirical Antifungal Therapy

Abstract Background: Invasive fungal infections (IFIs) are of serious concern in the management of immunocompromised patients (pts) with hematological disorders. Empiric antifungal therapy is recommended for neutropenic pts with persistent fever, because treatment after confirmation of fungal infection often produces poor outcomes. Micafungin (MCFG), one of the echinocandin families, was launched first in Japan in 2002, and has now been approved in more than 11 countries and areas including the USA and the EU. Although the efficacy and safety of MCFG against both Candida and Aspergillus infections has been shown in many clinical trials, there are few clinical study reports on the empiric therapy of a suspected fungal infection. Here, we report the multi-center study results of MCFG for the empiric antifungal therapy, which were conducted from April 2005 to September 2006 in Japan. Objective: This prospective study was performed to clarify the efficacy and safety of MCFG for the empirical antifungal therapy on suspected fungal infection in pts with hematological disorders and neutropenia. Methods: Study design: A multiple-center, open, uncontrolled study. The investigator registered pts with neutropenia (&lt; 1,000/μl) who met the following criteria to the Subject Registration Center. Suspected fungal infections were divided into two categories: possible fungal infection defined by positive clinical symptoms/findings and serological testing (beta-D-glucan or galactomannan) or diagnostic imaging (chest X-ray or CT scan), refractory fever defined by unexplained persistent fever (an axillary temperature higher than 37.5 °C) after the antibacterial treatment over 2 days and by positive clinical symptoms/findings. IFIs categorized as proven or probable were not included in this study. Efficacy evaluation was performed using an algorithm based on each of the evaluation of clinical symptoms/findings, imaging study findings, and serological tests. Results: 388 pts (M:234, F:154, mean age:57.8 years old) were registered. The mean dosage and duration of treatment with MCFG were 154.6±55.3 mg/day and 14.0±6.9 days, respectively. The main underlying hematological disorders were acute leukemia (61.3%), non-Hodgkin’s lymphoma (18.3%) and myelodysplastic syndrome (10.8%). The number of pts with hematopoietic stem cell transplantation (HSCT) was 76 (19.6%). The clinical response rate (CRR), excluding 4 non-evaluable pts was 63.3% (243/384): 60.1% (89/148) for pts with possible fungal infection and 65.3% (154/236) for pts with refractory fever, respectively. Even in persistent neutropenic pts whose neutrophil counts were &lt; 500/μL throughout the treatment with MCFG, the CRR was high enough: 46.9% (61/130). No difference was observed in the CRR among the main underlying hematological disorders. The CRR in pts with HSCT and other conditions were 63.2% (48/76) and 63.3% (195/308), respectively. Drug-related adverse events (DAEs) were observed in 16.8% (65/388). Serious DAEs such as elevation of serum bilirubin and renal dysfunction was observed in 0.52% (2/388). Conclusion: MCFG was confirmed to have high clinical efficacy and be safe for the treatment of suspected fungal infection in pts with hematological disorders and neutropenia.

A Comparison of Proposed Biosimilar and Originator Filgrastim for the Prevention of Neutropenia in Patients with Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Phase III, Randomized, Double-Blind Trial (The PIONEER study)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5133-5133 ◽  
Author(s):  
Kimberly Blackwell ◽  
Vladimir Semiglazov ◽  
Pedro Gascon ◽  
Roumen Nakov ◽  
Stefan Kramer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Group ◽  
Adverse Events ◽  
Lower Limit ◽  
Study Drug ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Pioneer Study ◽  
The Mean

Abstract Introduction: Biosimilars are biologics which have demonstrated highly similar safety, potency and purity to an originator product. Several biosimilars of recombinant human filgrastim, based on the originator Neupogen®, have become available in Europe since 2008 and are now in clinical use for the prevention of chemotherapy-induced neutropenia and hematopoietic stem cell mobilization. Filgrastim biosimilars are presently being developed for the U.S. market. Study design: A randomized, double-blind, four-group, multi-center phase III non-inferiority trial was performed with breast cancer patients treated with myleosuppressive chemotherapy. The two filgrastim products – proposed biosimilar, EP2006 (“biosimilar”) vs. originator (U.S.-licensed Neupogen®) - were compared regarding efficacy and safety. Patients included: women ≥18 years with histologically-proven breast cancer eligible for neoadjuvant or adjuvant treatment with docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC regimen) given for 6 cycles. Other key inclusion criteria included: Eastern Cooperative Oncology Group performance status ≤2 and adequate bone marrow function. Eligible patients were randomized to 4 groups with 2 of these groups alternating between the biosimilar and the originator filgrastim at the end of each cycle: 1) EP: treatment with EP2006 in all cycles; 2) EPNEU: EP2006 in Cycle 1, alternating between Neupogen and EP2006 in the following cycles; 3) NEUEP: Neupogen in Cycle 1, alternating between EP2006 and Neupogen in the following cycles; 4) NEU: treatment with Neupogen in all cycles. Patients received either biosimilar or originator filgrastim subcutaneously (daily dose of 5 µg/kg body weight) starting on Day 2 of each chemotherapy cycle until the absolute neutrophil count (ANC) recovered to 10×109/L after nadir or up to 14 days. Total duration of the study was 25 weeks: 3 weeks screening, 18 weeks treatment (total 6 cycles, 3 weeks each) and a follow-up visit 4 weeks after the last study drug administration. Primary objective was to assess the efficacy of the biosimilar compared to the originator with respect to mean duration of severe neutropenia (DSN) following Cycle 1 chemotherapy. A one-sided 97.5% confidence interval (CI) for the difference in the mean DSN calculated using ANCOVA model with factors “treatment” and “kind of therapy” and covariates “baseline ANC” was to be considered non-inferior if lower limit of this CI lies entirely above non-inferiority margin of -1 day. All secondary efficacy endpoints and safety endpoints were analyzed descriptively by treatment group. The study was conducted between December 2011 and June 2013. Results: Enrolled were 258 patients in 27 centers, of which 218 patients were randomized to treatment. The baseline characteristics were balanced between different groups. The per-protocol set included 204 patients out of 218 randomized patients. The safety set included 214 patients who received at least one dose of study drug. On average each patient received treatment for 8-9 days per cycle. The mean DSN in Cycle 1 was 1.17±1.11 days (biosimilar) and 1.20±1.02 days (originator); the mean difference in DSN was 0.04 days (97.5% CI, lower limit -0.26 days). The pre-defined non-inferiority criteria were met and the biosimilar was considered non-inferior to the originator filgrastim. The incidence of febrile neutropenia over all 6 cycles chemotherapy was comparably low in all treatment groups (EP: 2/40, 5.0%, EPNEU: 5/45, 11.1%, NEUEP: 1/44, 2.3%, NEU: 0/46, 0.0%). There was no obvious difference in incidences of treatment emergent adverse events between the treatment arms. Twelve patients experienced serious adverse events (EP: 5/53, 9.4% patients; EPNEU: 4/54, 7.4%; NEUEP: 1/55, 1.8%; NEU: 2/52, 3.8%). None of them were study drug related, including one death (in the EP treatment group due to pulmonary embolism). No subjects developed anti-drug antibodies. Conclusion: This large clinical study showed that efficacy and safety of the biosimilar was comparable to the originator filgrastim in prevention of neutropenia in patients with breast cancer. Repeated switching between the biosimilar and the originator filgrastim did not impact efficacy, safety or immunogenicity. Acknowledgment: The authors acknowledge the other investigators of the PIONEER study and acknowledge Gabor Stiegler, Sandoz Biopharmaceuticals for the medical writing. Disclosures Blackwell: Sandoz Biopharmaceuticals: Consultancy. Semiglazov:Sandoz Biopharmaceuticals: Consultancy. Gascon:Sandoz Biopharmaceuticals: Consultancy. Nakov:Sandoz Biopharmaceuticals: Employment. Kramer:Sandoz Biopharmaceuticals: Employment. Schwebig:Sandoz Biopharmaceuticals: Employment. Harbeck:Sandoz Biopharmaceuticals: Consultancy.

Review of Serum Voriconazole Concentrations and Correlations with Adverse Events and Efficacy

2009 ◽  
Vol 25 (3) ◽  
pp. 183-189
Author(s):  
Michael J Latran
Keyword(s):  
Adverse Events ◽  
Fungal Infections ◽  
Case Reports ◽  
Elevated Serum ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Efficacy And Safety ◽  
Data Synthesis ◽  
Additional Information ◽  
Search Terms

Objective: To review the available evidence regarding the monitoring of serum voriconazole concentrations in terms of efficacy and safety. Data Sources: A literature search of MEDLINE was conducted (1950–February 2009), with combinations of the following search terms: voriconazole, therapeutic drug monitoring, voriconazole serum concentrations, voriconazole levels, trough, and adverse events. Data Collection: All studies and case reports that evaluated serum voriconazole concentrations in adults were reviewed and considered for inclusion. Citations in identified articles were searched for additional information. Data Synthesis: Ten studies and case reports that evaluated serum voriconazole concentrations in terms of efficacy and safety in adults were identified and included in this review. Results from efficacy studies show an association between low serum voriconazole concentrations and disease progression. One study found that a lack of response occurred more often in patients with a serum voriconazole trough of 1 μg/mL or less (p = 0.02). Another study found that patients were more likely to fail voriconazole therapy for invasive fungal infections when serum concentrations were less than or equal to 2 μg/mL. In terms of safety, 6 studies showed an association between elevated serum voriconazole concentrations and adverse events. Conclusions: Available data suggest that serum voriconazole concentrations of 1 μg/mL or less are associated with therapeutic failures, whereas serum voriconazole concentrations of 6 μg/mL or more are associated with adverse events. Studies show that monitoring serum voriconazole concentrations may decrease the incidence of adverse events while increasing efficacy.

Propranolol in the Management of Infantile Hemangiomas: Clinical Response and Predictors

2012 ◽  
Vol 16 (3) ◽  
pp. 169-173 ◽  
Author(s):  
Alexandra Balma-Mena ◽  
Ajith Chakkittakandiyil ◽  
Miriam Weinstein ◽  
Perla Lansang ◽  
Nhung Ho ◽  
...  
Keyword(s):  
Cohort Study ◽  
Side Effects ◽  
Clinical Response ◽  
Retrospective Cohort ◽  
Analogue Scale ◽  
Optimal Dose ◽  
Duration Of Therapy ◽  
Predictors Of Response ◽  
Percent Improvement ◽  
The Mean

Background: Recent data suggest that propranolol is an effective treatment for infantile hemangiomas (IHs). Data on the optimal dose, duration of therapy, and predictors of response are currently lacking. Objective: To assess the clinical response to and predictors of propranolol use in the treatment of IH. Methods: Retrospective cohort study of 44 patients. Two independent assessors evaluated improvement by comparing serial digital photographs using a 100 mm visual analogue scale (VAS), where 5 mm change represented 10% change in the size or appearance of the IH. Results: Propranolol was started at a mean age of 7.8 (SD 8.21) months and was used for 7.3 (SD 4.8) months before weaning. The mean percent improvement compared to baseline (as measured by the VAS) was 78% (SD 23%). Minor adverse events were noted in 32% of patients. The most significant predictor of regrowth after weaning was a IH > 5 cm in size ( p = .017). Conclusions: Propranolol is effective in IH, but the side effects and the possibility of regrowth should be considered.

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