Comparative effectiveness of pegfilgrastim, filgrastim, and sargramostim prophylaxis for neutropenia-related hospitalization: two US retrospective claims analyses.

OBJECTIVE: Few studies have compared the effectiveness of filgrastim (FIL), pegfilgrastim (PEG), and sargramostim (SAR) to reduce the risk of febrile neutropenia (FN) associated with myelosuppressive chemotherapy (M-CT). Two large commercial database analyses were separately conducted to examine the incidence of neutropenia-related and all-cause hospitalizations associated with FIL, PEG, and SAR prophylaxis for patients receiving M-CT for non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, or solid tumors. METHODS: Separate retrospective US claims database analyses utilized patient data from January 1, 2004 to April 30, 2010 using the HealthCore Integrated Research Database (HIRD(SM)) and January 1, 2001 to August 31, 2009 using OptumInsight's (formerly Ingenix) database. Patients were ≥18 years old and treated with M-CT for NHL, Hodgkin lymphoma, and solid tumors. All identified M-CT cycles with prophylactic (first 5 days of cycle) FIL, PEG, or SAR were included in the analysis. Patterns of administration and incidence rates of all-cause and neutropenia-related hospitalization were examined on a per-cycle basis. RESULTS: In total, 9330 and 8762 patients with cancer, representing 30,264 and 24,215 chemotherapy cycles (28,189 and 22,649 (PEG), 1669 and 1351 (FIL), 406 and 215 (SAR)) from the HIRD(SM) and OptumInsight databases, respectively, were included in the separate database analyses. Both the HIRD(SM) and OptumInsight analysis showed that SAR and FIL prophylaxis had a higher risk of neutropenia-related hospitalization (SAR: OR = 3.48 [95%CI = 2.11, 5.74] and 2.81 [1.62, 4.87]; FIL: 1.78 [1.28, 2.48] and 2.36 [1.82, 3.06], respectively) and all-cause hospitalization (SAR: 2.18 [1.41, 3.36] and 2.41 [1.58, 3.68]; FIL:1.57 [1.25, 1.97] and 1.95 [1.60, 2.38], respectively) vs PEG. LIMITATIONS: Medical claims do not contain information about chemotherapy dose, and hospitalizations were not validated against the patient's chart. CONCLUSION: In this comparative effectiveness study, use of PEG was associated with a lower risk of neutropenia-related and all-cause hospitalizations compared to use of FIL or SAR prophylaxis.

Pharmacoeconomics of the myeloid growth factors: a critical and systematic review.

BACKGROUND: The pharmacoeconomics of the myeloid growth factors (MGFs) is an important topic that has received substantial attention in recent years. The use of the MGFs as primary prophylaxis to prevent febrile neutropenia (FN) has grown considerably over the past decade and professional guidelines regarding their use have broadened the settings in which these agents are indicated. Recent data also suggest a potential role for them in reducing infection-related and all-cause mortality. The cost and effectiveness of these agents will continue to gain visibility as companies pursue approval for biosimilar agents in the US, similar to their recent approval in Europe. OBJECTIVES: The objective of this paper is to review the available pharmacoeconomic literature on the MGFs, which is particularly timely in light of the recent passage of healthcare reform and the increasing focus on cost control. The cost of treating cancer in the US is rising faster than the already rapid increase in overall medical expenditure. The clinical utility and cost effectiveness of supportive care measures in oncology must therefore be weighed carefully. This review focuses on the use of different formulations of MGFs for primary and secondary prophylaxis of chemotherapy-induced neutropenia. METHODS: A MEDLINE search was performed to find studies that became available since the prior review of this topic was published in Pharmacoeconomics in 2003. RESULTS: Acceptable cost-minimization estimates for primary prophylaxis with the MGFs in patients receiving cancer chemotherapy have been provided by several studies in the US. Of the commonly used agents in the US, pegfilgrastim appears to be superior to the currently recommended dose and schedule of filgrastim in terms of cost minimization, and primary prophylaxis appears to be less costly than secondary prophylaxis. However, the cost benefits of primary prophylaxis in Europe are not as pronounced as in the US, due to the lower costs of medical care. Data continue to emerge suggesting a decreased risk of early mortality from averted infections as well as the possibility of a disease-specific mortality benefit through maintaining the relative dose intensity of chemotherapy with MGF support. CONCLUSION: This evidence will prove valuable in assessing the overall cost effectiveness and cost utility of the MGFs in patients receiving cancer chemotherapy.

Comparison of hospitalization risk and associated costs among patients receiving sargramostim, filgrastim, and pegfilgrastim for chemotherapy-induced neutropenia.

BACKGROUND: Sargramostim is a granulocyte-macrophage-colony-stimulating factor (GM-CSF). Unlike filgrastim and pegfilgrastim, which are granulocyte-colony-stimulating factors (G-CSFs), sargramostim activates a broader range of myeloid lineage-derived cells. Therefore, GM-CSF might reduce infection risk more than the G-CSFs. This study compared real-world infection-related hospitalization rates and costs in patients using G/GM-CSF for chemotherapy-induced neutropenia. METHODS: This retrospective matched-cohort study analyzed nationally representative health insurance claims in the United States from 2000 through 2007. The sample population included patients who received chemotherapy and G/GM-CSF. G/GM-CSF treatment episodes began with the first administration of G/GM-CSF and ended when a subsequent administration was >28 days after a prior administration. Sargramostim patients were matched 1:1 with filgrastim and pegfilgrastim patients based on gender and birth year. Outcomes included infection-related hospitalization rates and the associated costs. Hospitalization rates were analyzed using univariate and multivariate Poisson methods; covariates included myelosuppressive agents received, tumor type, anemia, and comorbidities. RESULTS: A total of 990 sargramostim-filgrastim and 982 sargramostim-pegfilgrastim matched pairs were analyzed. Cohorts were similar with regard to age, gender, and comorbid conditions. Several differences were observed with regard to tumor type, anemia, and chemotherapy, but no systematic trends were apparent. Sargramostim patients experienced a 56% lower risk of infection-related hospitalizations compared with filgrastim and pegfilgrastim patients. Infection-related hospitalization costs were 84% and 62% lower for sargramostim patients compared with patients treated with filgrastim and pegfilgrastim, respectively. CONCLUSIONS: Among patients with or at risk for chemotherapy-induced neutropenia, these data indicated that use of sargramostim was associated with a reduced risk of infection-related hospitalization and lower associated costs compared with filgrastim or pegfilgrastim.

Growth factors in leukemia.

The role of myeloid growth factors, such as granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, in the management of acute myeloid and acute lymphoblastic leukemias has been evaluated extensively in multiple clinical trials. Growth factors have been given before, concurrently, or sequentially with chemotherapy with the goal of reducing the duration of neutropenia and consequently the incidence and severity of infections, and improving the rate of remissions and overall survival. They also have been studied as chemotherapy-sensitizing agents in an effort to recruit dormant myeloid stem cells into the sensitive phase of the cycle. Additionally, growth factors, shown to stimulate proliferation and differentiation of leukemia cells in vitro, were evaluated as monotherapy in patients with acute leukemia. Most studies show modest improvement in the duration of the neutropenia, which does not consistently correlate with the severity of infection, rate or duration of remissions, or disease-free and overall survival. Attempts to enhance the chemosensitivity of the leukemic cells and decrease drug resistance failed to improve the rate of remission and survival in several large series. However, more recent reports suggested an improved outcome in younger patients with acute myeloid leukemia with normal karyotype. Several anecdotal case reports have shown that growth factor monotherapy can induce a complete remission in patients with acute leukemia. Data from the published clinical trials do not seem to support emergence of drug-resistant leukemia, worsening toxicity, and bone marrow failure with growth factor administration.

Meta-analysis of randomized controlled trials of prophylactic granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor after autologous and allogeneic stem cell transplantation.

PURPOSE: The primary objective of our meta-analysis was to determine whether prophylactic hematopoietic colony-stimulating factors (CSFs) after hematopoietic autologous and allogeneic stem-cell transplantation (SCT) reduced documented infections. Our secondary objectives were to determine whether prophylactic CSFs affected other outcomes including parenteral antibiotic therapy duration, infection-related mortality, graft-versus-host disease (GVHD), or treatment-related mortality. METHODS: We included studies if there was random assignment between CSFs and placebo/no therapy and CSFs were given after SCT and before recovery of neutrophils. From 3,778 reviewed study articles, 34 were included based on predefined inclusion criteria. All analyses were conducted using a random effects model. RESULTS: CSFs reduced the risk of documented infections (relative risk [RR] 0.87; 95% CI, 0.76 to 1.00; P = .05) and duration of parenteral antibiotics (weighted mean difference, -1.39 days, 95% CI, -2.56 to -0.22; P = .02) but did not reduce infection-related mortality (RR, 0.76; 95% CI, 0.41 to 1.44; P = .4). CSFs did not increase grade 2 to 4 acute GVHD (RR, 1.03; 95% CI, 0.81 to 1.31; P = .8) or treatment-related mortality (RR, 1.00; 95% CI, 0.78 to 1.29; P = .98). CONCLUSION: CSFs were associated with a small reduction in the risk of documented infections but did not affect infection or treatment-related mortality.

The economics of inclusion body processing.

Many recombinant proteins are often over-expressed in host cells, such as Escherichia coli, and are found as insoluble and inactive protein aggregates known as inclusion bodies (IBs). Recently, a novel process for IB extraction and solubilisation, based on chemical extraction, has been reported. While this method has the potential to radically intensify traditional IB processing, the process economics of the new technique have yet to be reported. This study focuses on the evaluation of process economics for several IB processing schemes based on chemical extraction and/or traditional techniques. Simulations and economic analysis were conducted at various processing conditions using granulocyte macrophage-colony stimulating factor, expressed as IBs in E. coli, as a model protein. In most cases, IB processing schemes based on chemical extraction having a shorter downstream cascade demonstrated a competitive economic edge over the conventional route, validating the new process as an economically more viable alternative for IB processing.

Granulocyte growth factors in the treatment of non-small cell lung cancer (NSCLC).

Neutropenia and subsequent infections are common events that limit treatment of non-small cell lung cancer (NSCLC). Granulocyte growth factors (G- and GM-CSF) have been introduced in clinical practice and their use has yielded a reduction of the infection risk related to chemotherapy and a dose increase of drug delivery. Randomized clinical trials have shown that granulocyte colony-stimulating factors and, more recently, the longer-acting pegylated granulocyte colony-stimulating factor (pegfilgrastim) effectively reduce the incidence and severity of neutropenia and of its complications. Recommendations for the use of haematopoietic colony-stimulating factors from the American Society of Clinical Oncology (ASCO) have been published in 1994 and updated in 1996, 1997 and 2000. Recently, moreover, National Comprehensive Cancer Network (NCCN) guidelines for the myeloid growth factors in cancer treatment make available. Chemotherapy-associated myelosuppression is a major limitation of anticancer therapy also in early stage, local advanced and metastatic NSCLC. Recently, dose-dense chemotherapy has been shown to improve the outcome in early stage breast cancer and non-Hodgkin's lymphoma. However, few randomized trials have been reported on chemotherapy with or without granulocyte growth factors as primary prophylaxis in NSCLC. Presently, there is no evidence for a benefit in response rate and survival from the use of granulocyte growth factors as support of chemotherapy, in particular, for locally advanced and metastatic NSCLC. In clinical practice, the role of granulocyte growth factors for NSCLC treatment should be limited following the guidelines. An appropriate use of granulocyte growth factors may reduce the overall cost of treatment and improve the quality of life, important aims in the treatment of patients with local advanced or metastatic NSCLC. In the future, we need to identify patients who can benefit from granulocyte growth factors for optimize the schedule and doses, in advanced disease and also, after the recent positive results of adjuvant chemotherapy, in early stages. This review summarizes the present knowledge on the use of granulocyte growth factors in NSCLC.

Effects of a formulary change from granulocyte colony-stimulating factor to granulocyte-macrophage colony-stimulating factor on outcomes in patients treated with myelosuppressive chemotherapy.

STUDY OBJECTIVE: To evaluate the effects on efficacy and safety of a formulary change from granulocyte colony-stimulating factor (G-CSF) to granulocyte-macrophage CSF (GM-CSF). DESIGN: Retrospective chart review. SETTING: Single-center academic institution. PATIENTS: Fifty-six patients aged 18 years or older with breast cancer, lung cancer, melanoma, Hodgkin's lymphoma, or non-Hodgkin's lymphoma who developed neutropenia within 4 weeks after treatment with myelosuppressive chemotherapy and who had been given five or more doses of CSF as primary or secondary prophylaxis from January 1995-March 2002. Twenty-nine patients treated before January 2000 were given G-CSF; after the formulary change in January 2000, 27 patients were primarily given GM-CSF. MEASUREMENTS AND MAIN RESULTS: The primary efficacy end point was time to an absolute neutrophil count of 1.5x10(3)/mm3 or greater after treatment with CSF. Second and third efficacy end points, respectively, were frequency of febrile neutropenia and effect of CSF treatment on schedule and dose intensity of subsequent chemotherapy cycles. Primary and secondary safety end points, respectively, were frequency of adverse events and use of resources used to manage these events. The time to neutrophil recovery was similar with G-CSF and GM-CSF. Febrile neutropenia was more common in the patients given GM-CSF. Chemotherapy dose delays also were more common in patients treated with GM-CSF, as was the frequency of fever. Use of resources (platelet and red blood cell transfusions, intravenous antibiotics, and hospitalizations) was greater in the patients treated with GM-CSF. CONCLUSION: The formulary change to GM-CSF was associated with a higher frequency of febrile neutropenia, resultant chemotherapy dose delays, more adverse events, and greater use of resources to manage the adverse events. These results suggest that G-CSF and GM-CSF are not therapeutically equivalent, with G-CSF having a superior safety and efficacy profile for the prevention of chemotherapy-induced neutropenic events.

Phase II clinical trial of local use of GM-CSF for prevention and treatment of chemotherapy- and concomitant chemoradiotherapy-induced severe oral mucositis in advanced head and neck cancer patients: an evaluation of effectiveness, safety and costs.

In the present open non-randomized phase II study we looked for effectiveness, safety, tolerability and costs of locally applied GM-CSF in preventing or treating mucositis in patients receiving chemotherapy or chemoradiotherapy for head and neck cancer. In addition to clinical mucositis scoring system, the effects of treatment with GM-CSF were evaluated by its impact on patient quality of life and by laboratory immunological assays such as serum proinflammatory cytokines, IL-2 and leptin. The trial was designed to assess the effectiveness of local GM-CSF treatment in two different settings: i) prophylaxis of mucositis; ii) treatment of mucositis. Prophylaxis was chosen for chemoradiotherapy treatments of high mucosatoxic potential, while curative treatment was reserved for chemotherapy or chemoradiotherapy treatments of lesser potential of inducing mucositis. From January 1998 to December 2001, 68 patients entered the study. The great majority of patients of both groups had head and neck cancer, were stage IV, PS ECOG 0-1, were habitual smokers and were treated with chemotherapy and concomitant (or sequential) chemoradiotherapy. Forty-six patients were included in the 'prophylactic' setting and 22 patients in the 'curative' setting. The main findings of our study are: only 50% of patients included in the 'prophylactic' setting developed mucositis; the duration of oral mucositis from appearance until complete remission was significantly shorter in the 'prophylactic' than in the 'curative' setting; the mean grade of oral mucositis at baseline, on day 3 of therapy and on day 6 of therapy was significantly lower in the 'prophylactic' than in the 'curative' setting; 24 (55.82%) patients in the 'prophylactic' setting had grade 3/4 oral mucositis at baseline compared to 25 (80.60%) patients in the 'curative' setting (p=0.048). Thirteen (30.23%) patients in the 'prophylactic' setting had grade 3/4 oral mucositis on day 3 of therapy compared to 19 (61.29%) patients in the 'curative' setting (p=0.015); 'prophylactic' setting was able to shorten grade 3/4 oral mucositis to grade 0/1 more effectively than the 'curative' one on day 6 of therapy (p=0.05). The present clinical trial is to date by far the largest study assessing the effectiveness of topical GM-CSF and it is the first study comparing the efficacy of topical GM-CSF in the 'prophylactic' setting, i.e., with the aim to prevent the chemoradiotherapy-induced oral mucositis, with that in the 'curative' treatment, i.e., the therapy for established oral mucositis. The topical application of GM-CSF was demonstrated to be effective for oral mucositis induced by chemotherapy and chemoradiotherapy regimens. Moreover, the 'prophylactic' setting was demonstrated to be more effective than the 'curative' one.

Economic evaluation of filgrastim, sargramostim, and sequential sargramostim and filgrastim after myelosuppressive chemotherapy.

Filgrastim alone and sequential sargramostim and filgrastim have been shown to be more effective than sargramostim alone in the mobilization of CD34(+) cells after myelosuppressive chemotherapy (MC). We sought to compare costs and resource use associated with these regimens. Data were collected prospectively alongside a multicenter, randomized trial of filgrastim, sargramostim, and sequential sargramostim and filgrastim. Direct medical costs were calculated for inpatient and outpatient visits and procedures, including administration of growth factors and MC. We followed 156 patients for 30 days or until initiation of high-dose chemotherapy. The main outcome measures were resource use and costs of inpatient and outpatient visits, platelet and red blood cell transfusions, antibiotic use, and apheresis procedures. Hospital admissions, red blood cell transfusions, and use of i.v. antibiotics were significantly more common in the sargramostim group than in the other treatment arms. In univariate and multivariable analyses, total costs were higher for patients receiving sargramostim alone than for patients in the other groups. Mean costs in multivariable analysis for the filgrastim and sequential sargramostim and filgrastim arms were not significantly different. Filgrastim alone and sequential sargramostim and filgrastim are less costly than sargramostim alone after MC, as well as therapeutically more beneficial.

GM-CSF versus G-CSF: engraftment characteristics, resource utilization, and cost following autologous PBSC transplantation.

BACKGROUND: G-CSF and GM-CSF have both been shown to decrease the time to hematopoietic recovery when administered after autologous BM or peripheral stem cell re-infusion. However, few studies have compared G-CSF and GM-CSF to determine which is the preferred myeloid growth factor. METHODS: This study compares a prospectively accrued cohort of 22 patients receiving GM-CSF with a historical cohort of patients who received G-CSF commencing Day + 6 after autologous PBSC transplantation. Patients were matched based on disease type and stage, CD34(+) cell dose/kg, conditioning regimen, and prior treatment. Time to myeloid engraftment, growth factor utilization, antibiotic utilization, fever incidence, and cost were compared. RESULTS: The median time to neutrophil and platelet engraftment was similar in the two groups (ANC > 500 /mm(3), GM-CSF 12 versus G-CSF 11, P = 0.69). There was a trend towards more days of temperature > 38.0 masculine C (six versus three, P = 0.05) and febrile neutropenia (three versus two, P = 0.06) in the GM-CSF arm. There was a trend towards increased use of i.v. antibiotics in the GM-CSF cohort (7.6 days versus 5.5 days, P = 0.06). More chest X-rays (1.5 versus 1.0, P = 0.03) were ordered, and more blood cultures drawn (4.2 versus 2.7, P = 0.05) as part of fever evaluation in the group treated with GM-CSF. Resource utilization based on actual wholesale pricing (AWP) favored the G-CSF cohort. Applying a sensitivity analysis, GM-CSF became cost-effective when priced below $94 per 250 micro g, despite greater resource utilization. DISCUSSION: This study suggests that engraftment characteristics are similar with GM-CSF and G-CSF following PBSC transplantation. Resource utilization for fever treatment and evaluation may be greater with GM-CSF. Determination of which agent is more cost-effective depends on institutional acquisition costs.

[Cost effectiveness of GM-CSF in the treatment of acute myeloblastic leukemia in aged patients: protocol of GOELAM Sa3]. / Intérêt thérapeutique et économique du GM-CSF dans le traitement des leucémies aiguës myéloblastiques du sujet âgé: protocole GOELAM Sa3.

A cost-effectiveness analysis was carried out from a randomized placebo-controlled protocol of GM-CSF during and after remission induction treatment for elderly patients with acute myeloid leukemia (AML). A retrospective economic analysis was carried out from the hospital perspective. A total of 240 patients with de novo AML and aged 55 to 75 years were enrolled. Overall survival and disease-free survival were analysed for efficacy within five years and expressed in gained life-years. Analysis was also conducted according to the protocol stratification: 55-64-year-old and 65-75-year-old patients. Global costs were estimated on the basis of patient medical records from inclusion to death or relapse. In all, 83 patients were evaluated from three centres, Besançon, Nancy and Nantes. Costs are expressed in French francs. Overall, total cost per patient amounted to FF 641,778 for placebo patients and to FF 587,048 for GM-CSF patients. For disease free-survival, costs were FF 357,167 for placebo patients and FF 320,736 for GM-CSF patients. For overall survival and disease free-survival the cost savings by GM-CSF were, respectively, FF 54,730 and FF 36,431. In the younger patient group savings were synonymous with GM-CSF. In all cases GM-CSF strategy induced benefit expressed as savings as well as efficacy.

Impact of pharmacy practices on the cost of colony-stimulating factor use in pediatric stem cell transplantation: an institution-based analysis.

PURPOSE: An evaluation of colony-stimulating factor (CSF) use in pediatric stem cell transplantation (SCT) was conducted to identify potential cost-efficiencies while preserving institutional standards of patient care. METHODS: Clinical and pharmacy records of the 55 SCTs performed during fiscal year 1995 were reviewed. Material costs per vial and per microgram, exclusive of preparation or overhead costs, were used. The best costing strategy was defined as the least expensive stocking and dispensing practice to deliver the drug actually used during the study period. RESULTS: CSFs were used in 35 of 55 transplants; 68% of usage was protocol-mandated to enhance engraftment; the remainder was associated with life-threatening complications of SCT. All use was consistent with published evidence-based guidelines. Changes in stocking and dispensing practices would result in an overall annual savings of $48,162 (fiscal year 1995 dollars), a 39% decrease in cost without a change in clinical application. CONCLUSIONS: Our analysis demonstrates that stocking and dispensing practices place significant fiscal burden in the care of pediatric-aged patients and must be carefully considered. This analysis presents a model for evaluating all components of drug cost from a global perspective, highlighting a need for examination of pharmacy and manufacturing as well as clinical practices.

Use of concurrent G-CSF + GM-CSF vs G-CSF alone for mobilization of peripheral blood stem cells in children with malignant disease.

There is limited experience in the mobilization of peripheral blood progenitor cells (PBPC) in children and the optimal method for PBPC mobilization is unknown. The present study was conducted to ascertain whether mobilization with G-CSF + GM-CSF (group I) provides some advantage over G-CSF alone (group II) in terms of collected CD34+ cells and hematopoietic recovery following myeloablative conditioning in children with malignancies. An economic analysis was also performed. Each group comprised 21 consecutive patients. The mean number of aphereses was 1.5+/-0.5 in group I and 1.2+/-0.46 in group II (NS). The mean number of CD34+ cells was 3.8 x 106+/-4.03/kg in group I and 4.2+/-5.4 in group II (NS). The mean number of total blood volumes (TBV) processed was 4.4+/-1.5 in group I and 4.3+/-1.5 in group II (NS). The mean duration of the procedure was 276+/-74.1 min in group I and 286.7+/-75.9 min in group II (NS), and the inlet flow was 45.1+/-12 ml/min in group I and 39.5+/-15.1 ml/min in group II (NS). No significant differences in the neutrophil and platelet engraftment probability were observed between the two groups. The mean overall cost of group II was not statistically significant from that of group I (US$ 9521+/-330 vs US$ 10201+/-1028, P = NS). The cost of mobilization was significantly higher in group I than in group II, conditioning regimen costs were similar in both groups and the costs related to the post-transplant period were similar in both groups. We conclude that PBPC mobilization with G-CSF + GM-CSF in children does not enhance hematological recovery in comparison with mobilization using G-CSF alone. However, the combination of G-CSF + GM-CSF does not significantly increase the overall cost of transplantation.

Economic and humanistic impact of adverse events associated with CSFs.

The current economic health care environment is causing considerable challenges for hospital pharmacy. As pharmacy managers attempt to deal with managing the costs associated with pharmaceuticals, there is considerable pressure to account for the clinical outcomes associated with drug therapy. Particularly in cancer treatment as high-cost biopharmaceuticals have infiltrated the care of these patients, pharmacy managers must account for reimbursement issues, clinical outcomes, patient satisfaction and demands, budgetary costs, and appropriate use of costly resources. Consequently, managers need to develop strategies to address these concerns. Ideally, pharmacoeconomics should be used to incorporate the costs of clinical outcomes and drug costs into the overall evaluation of drug therapy. Unfortunately, for a variety of reasons, the practical application of pharmacoeconomics is not universally employed and, as a result, most evaluations rely on only drug costs. A method to assess the economic impact of clinical outcomes associated with adverse drug events and cancer chemotherapy is described.

Granulocyte-macrophage colony-stimulating factor support in therapy of high-risk acute lymphoblastic leukemia in children.

BACKGROUND: Our purpose was to increase the dose intensity of chemotherapy and reduce the days with neutropenic fever in childhood high-risk (HR) acute lymphoblastic leukemia (ALL) by systematic use of granulocyte-macrophage colony-stimulating factor (GM-CSF). PROCEDURE: All children with HR-ALL in Finland during 1990-1996 were included. Two open-label study groups were formed: 1) 34 children diagnosed between January, 1992, and December, 1996, received seven or nine courses (depending on cranial RT or no cranial RT) of GM-CSF at 5 microg/kg s.c. daily until an absolute neutrophil count (ANC) of 1,000 x 10(6)/liter at scheduled places in the protocol and 2) 80 control children, those diagnosed between January, 1990, and December, 1991, plus all with significant coexpression of myeloid markers, did not receive GM-CSF. RESULTS: Dose intensity increased in patients who received regular GM-CSF support. The intensive phase of therapy, including induction, consolidation courses, and delayed intensification, was 33 days shorter (P < 0.001) in children with seven courses and 26 days shorter (P < 0.01) in those with nine courses of GM-CSF compared to controls. The number of infections during the whole ALL therapy was reduced by use of GM-CSF in children aged >5 years (P < 0.001), but not in those aged <5 years. The mean total duration of intravenous antibiotics per child was 39 days in the GM-CSF group and 48 days in the control group (P < 0. 001). Systematic use of GM-CSF was cost-effective. CONCLUSIONS: Systematic use of GM-CSF improved dose intensity by shortening the intensive treatment period by about 4 weeks. Use of GM-CSF reduced the days for inpatient antibiotics by about 1 week per child, which translates into reduced costs.

Cost analyses of adjunct colony stimulating factors for acute leukemia: can they improve clinical decision making.

Colony stimulating factors reduce the duration of neutropenia following intensive chemotherapy in a variety of settings, but the advantages in the management of leukemia are inconclusive. The variations in clinical results and the high costs of granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) have led to confusion over appropriate use for leukemia patients. In this paper, we reviewed published information on costs and cost-effectiveness of growth factors for childhood and adult leukemia patients. Medline and Healthstar databases were searched for original research articles that contain cost or cost-effectiveness analyses of G-CSF (filgrastim) and GM-SCF (sargramostim) in oncology cooperative group trials. Published manuscripts and abstracts presented at national or international oncology conferences were included. The cost of adjunct treatment was evaluated in two studies of pediatric ALL, one study of adult AML, and two studies of AML in older adults (>55 years). The use of G-CSF for children with ALL was associated with reductions in days to ANC recovery, fewer documented infections, a shorter duration of hospitalization, and small (but not significant) additional costs. In adult AML patients, benefits included a shortening of the duration of neutropenia and hospital stays, a lower incidence of infection and febrile episodes, less use of antibiotics, and cost savings of $2,230 and $2,310 in two studies and an increase if $120 in the third study. This summary suggests that economic analyses can provide useful information to assist clinical decision-making. For pediatric ALL patients, this information indicates that G-CSF use is unlikely to have significant cost implications, and its use should be based on clinical considerations. In studies of adult and older adult AML patients, both GM-CSF and G-CSF have clinical benefits and can be expected to lead to a decrease in overall costs.

The association between physician reimbursement in the US and use of hematopoietic colony stimulating factors as adjunct therapy for older patients with acute myeloid leukemia: results from the 1997 American Society of Clinical Oncology survey. Health Services Research Committee of the American Society of Clinical Oncology.

BACKGROUND/OBJECTIVES: Financial considerations play an important role in the delivery of medical care in the US. In 1996, revised guidelines from the American Society of Clinical Oncology (ASCO) indicated that granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) were unlikely to be harmful for older acute myeloid leukemia (AML) patients and suggested that physicians could consider their use in this setting. In 1997, the ASCO health services research committee evaluated whether physician reimbursement was a primary determinant in the decision to use G-CSF and GM-CSF in this clinical situation. PATIENTS AND METHODS: A questionnaire describing clinical scenarios for a 67-year-old man with newly diagnosed de novo AML was mailed to 1500 ASCO members who practiced medical oncology and hematology. Physicians were queried about their preferences for adjunctive CSF use following induction and consolidation chemotherapy. RESULTS: Of 1020 potentially eligible respondents, returned surveys were received from 672. Following induction chemotherapy, support for CSF use was 40%, similar in magnitude for that for non-use of these agents. The most important determinant of support for CSF use was being in a fee-for-service practice (P < 0.001). CONCLUSIONS: Physicians in the US are mixed in their support for CSFs for older AML patients. Support was high in settings where CSF use was accompanied by financial profit to the physician practice, and support was low otherwise.