Ceftriaxone plus amikacin in neutropenic patients: a report on 100 cases.

100 febrile patients with chemotherapy-induced neutropenia (less than 0.5 x 10(9)/l) were empirically treated by ceftriaxone (2 g daily in adults, 50 mg/kg daily in children, as a once daily injection) and amikacin (15-20 mg/kg daily). The mean age was 41 years (range 8-72). 51 patients had acute leukemia, 29 non-Hodgkin's lymphoma, 12 Hodgkin's disease, 8 other disorders. 23 febrile episodes were bacteriologically documented (gram-positive: 13 patients; gram-negative: 8 patients; Candida: 2 patients) including 13 cases of bacteremia; 10 were clinically documented, and 67 remained of undetermined origin. Apyrexia was obtained in 39 patients by ceftriaxone plus amikacin alone (success), in 36 patients after the addition of vancomycin and/or amphotericin B (improvement), whereas in the remaining 25 patients it was necessary to substitute the study drug. The failure rate was correlated to the duration of neutropenia: 0/13 when neutropenia less than 6 days; 3/41 (7%) when 6-10 days; 22/46 (48%) when greater than 10 days. Only 2/20 (10%) of patients with neutropenia greater than 20 days were treated with ceftriaxone plus amikacin alone. 9 of the 23 bacteriologically documented episodes were successes (including 6 of the 11 cases due to Staphylococcus), 7 were improvements and 7 were failures (including the 3 cases due to Pseudomonas). No side effects were seen. Ceftriaxone plus amikacin is an effective firstline antibiotic combination in the treatment of febrile neutropenic patients.     

Piperacillin-tazobactam is more effective than ceftriaxone plus gentamicin in febrile neutropenic patients with hematological malignancies: a randomized comparison

GOALS: Efficacy and costs of empirical antibacterial therapy in febrile neutropenic patients are important issues. Several strategies have been reported to be similarly effective: monotherapy with cefepime, ceftazidime or a carbapenem or duotherapy with an antipseudomonal beta-lactam antibiotic or ceftriaxone in combination with an aminoglycoside. Piperacillin-tazobactam monotherapy is promising, but its role in this setting still has to be defined. PATIENTS AND METHODS: Of 212 consecutive febrile episodes in 130 neutropenic patients with hematological malignancies randomized to receive either piperacillin-tazobactam (4.5 g every 8 h; group A) or ceftriaxone (2 g once daily plus gentamicin 5 mg/kg once daily; group B), 183 episodes (98 group A, 85 group B) were evaluable for response. RESULTS: Defervescence within 72 h without modification of the antibiotic therapy was achieved in 56/98 episodes (57.1%) in group A and in 30/85 (35.3%) in group B (P=0.0047). If fever persisted, teicoplanin plus gentamicin (group A) or teicoplanin plus ciprofloxacin (group B) were added. All patients still febrile then received meropenem, teicoplanin and amphotericin B. With these modifications of antibiotic therapy, 89.8% of patients in group A had responded at 21 days but only 71.8% in group B (P=0.005). The mean total antibiotic drug cost in group A was only 39.4% of that in group B (euro 445 versus euro 1129; P=0.010). CONCLUSION: Piperacillin-tazobactam monotherapy is significantly more effective and cost-efficient than ceftriaxone plus gentamicin as first-line therapy in febrile neutropenic patients with hematological malignancies.     

Pegfilgrastim for chemotherapy-induced neutropenia

Many chemotherapy regimens cause myelosuppression, which can result in febrile neutropenia and potentially lead to serious infections. The risk of neutropenia and its complications can be reduced with filgrastim, a granulocyte-colony-stimulating factor. Filgrastim is safe and effective, but it is cleared rapidly from the body (predominantly through the kidneys) and requires daily administration for up to 14 days. A pegylated form of filgrastim, pegfilgrastim, has been developed by attaching a polyethylene glycol molecule to filgrastim. Pegfilgrastim has an extended circulation half-life and self-regulating, patient-specific pharmacokinetics, making it possible to give the treatment as a single dose once per chemotherapy cycle. Clinical trials have shown that a single, subcutaneous dose of pegfilgrastim is as safe and effective as daily filgrastim injections in patients treated with myelosuppressive chemotherapy. In addition, a single, 6 mg fixed dose of pegfilgrastim per chemotherapy cycle is sufficient in adult patients, regardless of their body weight, making pegfilgrastim a simple, effective, and well-tolerated option for managing chemotherapy-induced neutropenia.     

Tobramycin once versus three times daily, given with penicillin G, to febrile neutropenic cancer patients in Norway: a prospective, randomized, multicentre trial

OBJECTIVES: Penicillin G with an aminoglycoside is the standard initial empirical treatment in febrile neutropenia in Norway. It has been argued that giving the aminoglycoside once daily to neutropenic patients with Gram-negative bacteraemia may be hazardous when penicillin G is the beta-lactam antibiotic. We questioned this argument and hypothesized that tobramycin once daily was as efficacious as three times daily. METHODS: We conducted a randomized prospective multicentre study, comparing the efficacy of tobramycin 6 mg/kg once (arm A) versus three times (arm B) daily, plus penicillin G 5 million IU x 4, in febrile neutropenic cancer patients. Primary outcome: modification of the antibiotic regimen. RESULTS: One hundred and seventy-four patients were evaluable for intention-to-treat analyses. One hundred and fifty-five patients had lymphoma or leukaemia as the underlying cancer diagnosis. In arm A, 35 of 88 patients and in arm B, 34 of 86 patients, that is 40% in both arms had no modification of the antibiotic regimen. No patients died while participating in the study. Upon modification of the antibiotic regimen, all patients were successfully treated. The increase in serum creatinine was modest and similar in the two treatment groups. CONCLUSIONS: When administered with penicillin G, tobramycin given once daily was as efficacious and safe as tobramycin given three times daily in cancer patients with febrile neutropenia in Norway, provided the regimen was modified according to the clinical response.     

The prevalence of pain in a pediatric and young adult cancer population

The prevalence and nature of pain in the population of children and young adults with malignancy treated by the Pediatric Branch of the National Cancer Institute were assessed over a 6 month period. One hundred and thirty-nine patients were evaluated during 161 in-patient days and 195 out-patient clinic visits. Approximately 50% of the patients assessed in the hospital and 25% of the patients assessed in the out-patient clinic were found to be experiencing some degree of pain at the time of assessment. Therapy-related pain predominated in both in-patients and out-patients; only one-third of the pain experienced by in-patients and less than 20% of the pain experienced by out-patients was due to tumor. Tumor pain was due primarily to bony invasion. In order to control pain in those individuals experiencing pain, narcotic analgesics were being used by one-half of the in-patients and one-third of the out-patients. Overall pain control was good, with the medium visual analogue scale score being 26 mm on a 0-100 mm scale. During the study period 7 patients were identified to have chronic pain for greater than 1 year following eradication of all known tumor from the site of pain. One was receiving massive doses of narcotics (120 mg/day of methadone) apparently out of proportion to his underlying pain.     

Are shorter courses of filgrastim prophylaxis associated with increased risk of hospitalization?

BACKGROUND: In clinical trials in patients receiving myelosuppressive chemotherapy, 10-11 days of prophylaxis with filgrastim has been found to reduce the incidence of febrile neutropenia. In clinical practice, however, many patients receive shorter courses of therapy, even though the effectiveness of this regimen is unknown. OBJECTIVE: To examine the relationship between duration of filgrastim prophylaxis and risk of hospitalization in patients receiving chemotherapy for non-Hodgkin's lymphoma (NHL), breast cancer, or lung cancer. METHODS: Using a large, automated, US healthcare claims database, we identified all adults who received chemotherapy for NHL, breast cancer, or lung cancer between 1998 and 2002. For these patients, we identified their first course of chemotherapy and each unique cycle within that course. We then focused attention on all patient cycles in which filgrastim was administered on or before cycle day 5 (filgrastim prophylaxis). Pooling all such cycles, we examined the relationship between duration of filgrastim prophylaxis and risk of hospitalization for neutropenia or infection and risk of hospitalization for any reason, using generalized estimating equations. RESULTS: Mean +/- SD duration of filgrastim prophylaxis was 6.5 +/- 3.1 days across 332 cycles for 133 NHL patients, 6.1 +/- 2.9 days across 482 cycles for 205 breast cancer patients, and 4.3 +/- 3.1 days across 522 cycles for 260 lung cancer patients. In multivariate analyses, risk of hospitalization for neutropenia or infection was found to decline with each additional day of filgrastim prophylaxis for patients with NHL (OR 0.81; p = 0.003), breast cancer (OR 0.77; p = 0.001), and lung cancer (OR 0.91; p = 0.084). Risk reductions with each additional day of prophylaxis ranged from 15% to 19% for patients with NHL, 17% to 23% for those with breast cancer, and 8% to 9% for those with lung cancer. Similar reductions in risk were noted for all-cause hospitalization. CONCLUSIONS: Among patients with NHL, breast cancer, or lung cancer, shorter courses of filgrastim prophylaxis may increase the risk of hospitalization.     

Pegfilgrastim

Granulocyte colony stimulating factor (G-CSF) has proven efficacy in the prophylaxis of chemotherapy induced neutropenia and is associated with a reduction in the duration of neutropenia, febrile neutropenia, hospitalisation and intravenous antibiotic use. It is an effective mobiliser of peripheral blood progenitor cells and is used in many countries to mobilise and provide a source of stem cells for autologous and allogeneic bone marrow transplantation. The longevity of G-CSF action is limited by its short half-life, necessitating daily injections. Pegfilgrastim (Neulasta, Amgen, Inc.) is a novel form of filgrastim (G-CSF) with a sustained duration of action. Single dose pegfilgrastim has been shown to be as safe and effective as daily filgrastim in reducing the incidence of chemotherapy induced neutropenia. Pegfilgrastim provides clinical and quality of life benefits for patients as a result of its once per cycle administration. It is licenced in the US for use in the prophylaxis and treatment of chemotherapy induced neutropenia. Clinical trials to evaluate its ability to mobilise peripheral blood progenitor cells are ongoing.     

Netilmicin plus ceftriaxone versus amikacin plus ceftriaxone in the treatment of infections in granulocytopenic patients.

For the treatment of febrile episodes in granulocytopenic cancer patients, a combination of bactericidal and intravenously administered broad spectrum agents is recommended. An aminoglycoside plus a beta-lactame (piperacillin, azlocillin or IIIrd generation cephalosporins) are the drugs of first choice in an empiric approach. Because of frequent parenteral interventions (e.g. catheters, cannulations) in thrombopenic patients with multifactorial immunosuppression, we consider the application of once daily drugs, such as ceftriaxone, netilmicin or amikacin. For single dose treatment (1st day two applications), we used ceftriaxone in combination with netilmicin or amikacin as the first approach and retrospectively evaluated 47 patients for efficacy and safety.     

Pegfilgrastim

Granulocyte colony stimulating factor (G-CSF) has proven efficacy in the prophylaxis of chemotherapy induced neutropenia and is associated with a reduction in the duration of neutropenia, febrile neutropenia, hospitalisation and intravenous antibiotic use. It is an effective mobiliser of peripheral blood progenitor cells and is used in many countries to mobilise and provide a source of stem cells for autologous and allogeneic bone marrow transplantation. The longevity of G-CSF action is limited by its short half-life, necessitating daily injections. Pegfilgrastim (Neulasta^TM, Amgen, Inc.) is a novel form of filgrastim (G-CSF) with a sustained duration of action. Single dose pegfilgrastim has been shown to be as safe and effective as daily filgrastim in reducing the incidence of chemotherapy induced neutropenia. Pegfilgrastim provides clinical and quality of life benefits for patients as a result of its once per cycle administration. It is licenced in the US for use in the prophylaxis and treatment of chemotherapy induced neutropenia. Clinical trials to evaluate its ability to mobilise peripheral blood progenitor cells are ongoing.     

Economic aspects of empiric antibiotic therapy for febrile neutropenia in children with cancer

Several antibiotic regimens have been proposed worldwide for empiric treatment of febrile neutropenia in children with cancer, but none of them shows clear advantages in terms of clinical efficacy. Therefore, other parameters, including drug acquisition costs, should be considered in the selection of treatment. Children receive a "fraction" of a standard daily dose, and this fraction is generally calculated on the basis of body weight; therefore, the cost of each day of therapy is determined by the packages available for each single drug. We calculated the acquisition costs of various drugs proposed for the empiric treatment of febrile neutropenia in children with cancer, and then we estimated the daily cost of therapy referred to different patient weights. In general, the combination regimen with ceftriaxone plus aminoglycoside turned out to be less expensive than other regimens (including monotherapy with third-generation cephalosporins or carbapenems).     

Ceftriaxone for the treatment of febrile episodes in nonneutropenic patients with hematooncological disease or HIV infection: comparison of outpatient and inpatient care

BACKGROUND: Patients with hematooncological disease or HIV infection and febrile episodes are usually treated in hospital with broad-spectrum antibiotics. The aim of this observational study was to assess the feasibility of ambulatory parenteral antibiotic therapy in hematooncological or HIV-infected patients with confirmed or suspected infection. METHODS: The results in an outpatient treatment group were compared with those obtained in a group initially treated in hospital. Data were gathered on 90 outpatients and 72 inpatients. The inclusion criteria were fever > or =37.5 degrees C with an identified focus of infection, fever > or =38.0 degrees C of suspected bacterial origin with no identified focus of infection, leukocytosis > or =9,000/microl or C-reactive protein elevation > or =10 mg/l. RESULTS: Eighty outpatients and 69 inpatients were evaluable. Treatment in the outpatient group was begun with ceftriaxone. This led to defervescence in 87.5% of cases. The mean treatment duration was 7.1 days. Comparison of results in the outpatients with those initially hospitalized for treatment showed similar success rates. The mean hospital stay in the latter group was 12.9 days. CONCLUSIONS: Ceftriaxone represents an effective treatment for outpatient management of febrile episodes in patients with hematooncological disease or HIV infection. Outpatient treatment is more cost-effective than inpatient care.     

Treatment of typhoid fever with ceftriaxone for 5 days or chloramphenicol for 14 days: a randomized clinical trial.

To compare the therapeutic efficacy of ceftriaxone given once daily for 5 days and chloramphenicol given four times daily for 14 days, a controlled trial was carried out with 59 patients who were culture positive for Salmonella typhi. Ceftriaxone was given to 28 patients in once-daily intravenous doses of 75 mg/kg of body weight to children and 4 g to adults for 5 days; chloramphenicol was given to 31 patients at a dosage of 60 mg/kg/day until defervescence and then at 40 mg/kg/day to complete 14 days of treatment. All Salmonella isolates were susceptible to both antibiotics. Clinical cures (defervescence without complications, no relapse, and no need for further treatment) occurred in 79% of the patients treated with ceftriaxone and 90% of those treated with chloramphenicol (P = 0.37). On the third day of treatment, blood cultures were positive for S. typhi for 60% of the patients in the chloramphenicol group and 0% of the ceftriaxone group (P = 0.001). Defervescence occurred in half the patients in both groups during the first 7 days, but on days 9 to 13 after the start of treatment, nine patients in the ceftriaxone group, compared with six patients in the chloramphenicol group, remained febrile (P = 0.4). The median hematocrit and total leukocyte counts at day 14 were significantly lower for the chloramphenicol group than those for the ceftriaxone group (P = 0.01 and P = 0.02, respectively). These results indicate that the effects of therapy with ceftriaxone for typhoid fever differed from those of chloramphenicol therapy in that blood cultures became negative earlier, prolonged fever persisted in some patients, and bone marrow suppression was reduced. We conclude that a short, 5-day course of ceftriaxone is a useful alternative to conventional 14-day chloramphenicol therapy in the treatment of typhoid fever.     

Three-day treatment of typhoid fever with two different doses of ceftriaxone, compared to 14-day therapy with chloramphenicol: a randomized trial.

Fifty-nine adult Filipino patients suffering from typhoid fever documented by blood culture were randomly allocated to one of three different drug regimens. Nineteen patients received 3 g ceftriaxone iv once daily for three days. Twenty patients received 4 g ceftriaxone iv once daily for three days and 20 patients received oral chloramphenicol 3 g daily in divided doses for two days followed by 2 g daily for 12 days. Eighteen patients were cured (95%) with 3 g of ceftriaxone for three days. All patients receiving 4 g ceftriaxone per day for three days or chloramphenicol for 14 days were cured. In the ceftriaxone groups two patients developed typhoid fever 30 and 45 days respectively after completion of treatment and one further patient had evidence of reinfection. Three patients relapsed within 15 to 17 days in the chloramphenicol group. Fever subsided in most patients between six and eight days, with three patients having a prolonged and moderate fever for 11 days in the ceftriaxone groups. This study suggests that a short treatment of three days of typhoid fever with ceftriaxone (3 or 4 g once daily) is adequate and not hazardous as far as relapses are concerned.     

A prospective,randomized, double-blind multicenter comparison of parenteral ertapenem and ceftriaxone for the treatment of hospitalized adults with community-acquired pneumonia

BACKGROUND: Ertapenem is a once-daily parenteral beta-lactam licensed in the United States in November 2001 and in Europe in May 2002. OBJECTIVE: This study compared the efficacy and safety profiles of ertapenem with those of ceftriaxone for the treatment of hospitalized adult patients with serious community-acquired pneumonia (CAP) requiring parenteral therapy. METHODS: In this prospective, double-blind (with sponsor blinding), multicenter study, adult patients with CAP were stratified by Pneumonia Severity Index (< or = 3 or > 3) and age (< or = 65 or > 65 years) and randomized (2:1) to receive IV or intramuscular (IM) ertapenem 1 g once daily or IV or IM ceftriaxone 1 g once daily. Investigators could switch patients to an oral antimicrobial agent if clinical improvement was shown after at least 3 days of parenteral therapy. RESULTS: A total of 364 patients were randomized to treatment: 239 to the ertapenem group and 125 to the ceftriaxone group. Three patients in the ertapenem group and 2 in the ceftriaxone group did not receive study therapy. Of the treated patients, 77.1% (182/236) of patients in the ertapenem group and 75.6% (93/123) in the ceftriaxone group were clinically evaluable. Among clinically evaluable patients, the mean (SD) durations of parenteral and total (parenteral plus optional oral) therapy were 5.5 (2.6) and 11.5 (2.7) days for ertapenem and 5.6 (2.8) and 11.7 (3.0) days for ceftriaxone, respectively. Streptococcus pneumoniae was the most frequently isolated pathogen in both treatment groups. Cure rates were 92.2% for clinically evaluable patients in the ertapenem group and 93.6% for those in the ceftriaxone group (95% CI for the difference, adjusted for stratum, -8.6 to 5.7), fulfilling the criteria for statistical equivalence. At completion of parenteral therapy, 94.7% of patients in the ertapenem group and 95.8% in the ceftriaxone group showed clinical improvement. Infused vein complications (ertapenem, 3.4% [8/236]; ceftriaxone, 7.3% [9/123]) and elevated transaminase levels (ertapenem, 6.3% [13/207]; ceftriaxone, 7.1% [8/113]) were the most common adverse events in both groups. CONCLUSIONS: In this study of hospitalized adult patients, ertapenem therapy, with an oral switch option, was as effective as ceftriaxone with the same oral switch option for treatment of CAP requiring initial parenteral therapy. The overall safety profiles of the 2 drugs were comparable.     

Safety of granulocyte colony-stimulating factor (filgrastim) in intubated patients in the intensive care unit: interim analysis of a prospective, placebo-controlled, double-blind study

OBJECTIVE: To investigate the safety of the granulocyte colony-stimulating factor filgrastim in the prevention of nosocomial infections in intubated patients in the intensive care unit (ICU), with special emphasis on the possible deleterious effect on acute respiratory distress syndrome (ARDS) and the development of multiple organ dysfunction (MOD). DESIGN: Predetermined, interim analysis of a prospective, randomized, placebo-controlled, double-blind trial. SETTING: University hospital medical-surgical ICU. PATIENTS: A total of 59 consecutive ICU patients, aged >18 yrs, admitted to the ICU no more than 12 hrs before the study, intubated because of ventilatory insufficiency no more than 48 hrs before the study, expected to stay in the ICU for >48 hrs, and had informed consent from the next relative. INTERVENTIONS: Patients were randomized to receive either placebo or 300 microg of filgrastim subcutaneously once daily for 7 days. MEASUREMENTS AND MAIN RESULTS: No significant differences were found in the number of patients developing ARDS (2 of 20 in the placebo group vs. 0 of 22 in the filgrastim group), disseminated intravascular coagulation (3 of 27 vs. 3 of 29), acute renal failure (1 of 27 vs. 1 of 23), or change in MOD. Data analysis showed nosocomial infections in 11 of 29 patients in the placebo group and in 7 of 30 patients in the filgrastim group (p = .266). The median (range) length of ICU stay was 8 (1-34) days in the placebo group and 6 days (1-28) in the filgrastim group. The day 28 mortality rate was 17% (5 of 29) in the placebo group and 13% (4 of 30) in the filgrastim group. No drug-related adverse events occurred. CONCLUSION: Filgrastim is safe in intubated ICU patients, with no excess risk for development of ARDS or MOD.     

Comparison of cefepime versus ceftriaxone-amikacin as empirical regimens for the treatment of febrile neutropenia in acute leukemia patients

BACKGROUND: High-intensity regimes of chemotherapy have led to longer and more severe episodes of neutropenia with a resulting increase in morbidity and mortality due to infections. Which empiric antibiotic regimen to use in these cases is still under debate. METHODS: We performed a randomized comparative study to evaluate the efficacy of cefepime versus ceftriaxone plus amikacin as the initial treatment in an escalating, empirical, antibiotic therapy regimen in febrile neutropenic patients. Both adults and children were included. All patients had less than 500 neutrophils/microl at the time of infection. Patients were randomized to receive either cefepime or ceftriaxone plus amikacin. If infection continued 72 h later, patients in both groups received vancomycin, and if infection had not disappeared 7 days after starting antibiotics, amphotericin B was started. RESULTS: Twenty patients were included in each group. Both treatment and control groups were comparable for age and sex, among other factors. There were 18 cures in the cefepime group and 17 in the ceftriaxone plus amikacin group (p = 0.9). No patient discontinued therapy because of toxicity. CONCLUSIONS: Cefepime is a safe and very effective therapy for patients with acute leukemia and febrile neutropenia; in addition, it is a cheaper regimen in our country, and lacks the potential toxicity of the aminoglycosides.     

Safety and local tolerability of intramuscularly administered ertapenem diluted in lidocaine: a prospective, randomized, double-blind study versus intramuscular ceftriaxone

BACKGROUND: Ertapenem is a new, structurally unique, parenteral beta-lactam antimicrobial agent that can be administered once daily. OBJECTIVE: This study compared the local tolerability of ertapenem 1 g once a day administered intramuscularly (IM) versus IM ceftriaxone, with both drugs reconstituted in lidocaine. METHODS: In this prospective, double-blind, multicenter study, adult patients with lower respiratory tract infection, skin infection, or urinary tract infection requiring initial parenteral therapy were randomly assigned in a 3:1 ratio to treatment with IM ertapenem 1 g once daily or IM ceftriaxone 1 g once daily. Although study drugs were administered by unmasked personnel, the patients, investigators, and the sponsor medical reviewer were blinded. Patients who improved clinically could be switched to oral amoxicillin-clavulanate after at least 2 days of IM therapy. Tolerability and safety analyses were carried out for the treated population, and efficacy analyses were performed for the modified intent-to-treat population. RESULTS: A total of 117 patients were randomized. The 87 patients in the ertapenem group and 30 in the ceftriaxone group received IM therapy for a mean duration of 4.1 and 3.8 days, respectively. During treatment, 35.6% (31/87) of patients treated with ertapenem and 43.3% (13/30) of those treated with ceftriaxone experienced > or =1 symptom at the local injection site; the most common symptom was tenderness, followed by pain. Symptoms were moderate to severe in only 1 patient (1.1%) in the ertapenem group and 3 patients (10.0%) in the ceftriaxone group. Clinical drug-related adverse events were reported during IM therapy in 14 patients (16.1%) in the ertapenem group and 5 patients (16.7%) in the ceftriaxone group. Mean +/- SD creatine kinase concentrations, measured in all patients, were 204.8+/-234.8 U/L at the end of IM ertapenem therapy and 382.9+/-721.1 U/L at the end of IM ceftriaxone therapy; at follow-up, values had returned to normal or had decreased in all cases. CONCLUSIONS: Ertapenem 1 g (reconstituted in lidocaine) administered once daily IM was generally well tolerated. The tolerability and safety profiles of IM ertapenem therapy in this study were comparable to those of IM ceftriaxone therapy.     

Filgrastim therapy in acute nonlymphoblastic leukemia

AIM: To specify effects of the granulocytic colony-stimulating factor (G-CSF) in the treatment of acute nonlymphoblastic leukemia. MATERIAL AND METHODS: Thirteen patients with acute myeloid leukemia (AML) were treated in the Hematological Clinic of the Higher Medical Institute in Plovdiv in 1996-1998. All of them received a standard induction therapy with cytosin arabinoside + daunorubicin (7 + 3 days). During the first neutropenic phase (neutrophils < 0.5 x 10(9)/l) G-CSF filgrastim was applied (5 microg/kg/day, s.c.) until a recovery of the neutrophil count reached > 1.0 x 10(9)/l and was maintained for 3 successive days. The control group consisting of patients matched by age, gender, an AML cytomorphologic variant was given the same therapy but filgrastim. RESULTS: The study group showed quicker recovery of the neutrophil count (12.6 vs 16.8 days), reduced febrile period (9.8 vs 12.4 days) and shorter duration of parenteral antibiotic treatment (9.8 vs 12.4 days) compared to controls. No statistically significant difference between both groups was found in the duration of the antimycotic treatment (p > 0.05). No cytological signs of aggravation of basic disease were absent in patients who received filgrastim. CONCLUSION: Administration of G-CSF in AML is useful as it promotes rapid overcoming of neutropenia and its complications.     

Pegfilgrastim for the prevention of chemotherapy-induced febrile neutropenia in patients with solid tumors

Introduction: Neutropenia and febrile neutropenia are the most common and most severe bone marrow toxicities of chemotherapy. Recombinant granulocyte-colony stimulating factors (G-CSFs), both daily (filgrastim and biosimilars, and lenograstim) and long-acting (pegfilgrastim and lipegfilgrastim) formulations, are currently available to counteract the negative consequences of these side effects.

Areas covered: The purpose of this article is to review the physiopathology of chemotherapy-induced febrile neutropenia and its consequences, and the current evidence regarding the pharmacological properties, clinical efficacy and cost-effectiveness of pegfilgrastim as a strategy to prevent chemotherapy-induced febrile neutropenia in patients with solid tumors.

Expert opinion: Chemotherapy-induced febrile neutropenia and its complications are still a major health-care concern, and the inappropriate employment of G-CSFs in clinical practice can partially explain its burden. Pegfilgrastim has pharmacological advantages over daily G-CSFs that makes it easily administrable, thus reducing the chance of incorrect delivery. The once-per-cycle administration might explain the findings derived from observational studies suggesting a possible superior efficacy of pegfilgrastim over daily G-CSFs. For patients at higher risk of failure with daily G-CSF prophylaxis (e.g. risk of non-compliance, difficulties on performing regular hemograms, high risk of developing febrile neutropenia), pegfilgrastim might be the most appropriate option.     

Estimating resource use and cost of prophylactic management of neutropenia with filgrastim

The study objective is to develop a methodology for the measurement of time, resource use and cost of the prophylactic management of neutropenia with filgrastim in different settings where the drug is routinely used: in-hospital care, outpatient care and home care. The activity-based costing method is used to analyse the cost of managing prophylactically neutropenia and comprises four steps. First, department heads in each of the chosen settings were selected and interviewed to obtain key elements in the workflow that involves the management of neutropenia, followed by the second step involving in-depth, structured interviews of key personnel. The third step was the measurement of the time required for frequently occurring activities in monitoring neutropenia and the administration of filgrastim by a study nurse. Finally, information on resource unit costs and personnel salaries were collected from the administration units to calculate an average cost. Sensitivity analyses were undertaken on estimated variables in the study. A list of eight to 14 consecutive activities linked to the prophylactic management of neutropenia was observed. The number and type of activities do not differ between an in-hospital oncology ward and an outpatient setting except for blood samplings. The difference is more pronounced between hospital and home care settings, as in the latter the patient performs many of the activities him/herself. The cost estimate per setting for prophylactic drug use is 6.30 Euros for in-hospital care, 3.67 Euros for outpatient care and 5.49 Euros for home care. Taking the two most frequently occurring scenarios per chemotherapy cycle (i.e. with or without febrile neutropenia), the following cost estimates are obtained: 60.41 Euros for a patient with febrile neutropenia and 56.77 Euros for a patient without febrile neutropenia, excluding drug costs. With the activity-based costing method it is possible to accurately demonstrate cost savings in the management of neutropenia using the newer drug therapies.