Economic analysis of lenograstim in the correction of neutropenia following chemotherapy for non-Hodgkin's lymphoma

A prospective economic analysis of lenograstim and placebo was performed as part of a randomised double-blind trial in 162 patients receiving chemotherapy for non-Hodgkin's lymphoma (NHL). The primary clinical end-point was the percentage of patients experiencing > or = 1 documented infection in each treatment group. The cost of hospitalisation and the cost of medical services used were the primary economic end-points. Economic analysis was based on the French Hospital perspective. Over the 56-day study period, patients in the placebo group received more days of inpatient intravenous (8.9 vs 5.3 days; p < 0.01) and oral (5.3 vs 4.2 days) antibiotic therapy than those in the lenograstim group. This difference was due to a higher rate of documented infection in the placebo group. Patients treated with placebo also spent more days in hospital for reasons other than administration of chemotherapy (18.5 vs 14.4; p < 0.05). The number of days of chemotherapy was significantly greater in the lenograstim group than in the placebo group (19.4 vs 17.5; p < 0.001) because of shorter delays between chemotherapy cycles in the lenograstim group. The use of lenograstim to prevent chemotherapy-induced neutropenia in patients with NHL was associated with a reduction in total direct medical costs (excluding the cost of lenograstim) of FF7297 as a result of reduced patient morbidity. Furthermore, the higher rate of completion of chemotherapy in the lenograstim group may lead to better long term survival; this observation deserves further clinical investigation.     

Lenograstim: a review of its use in chemotherapy-induced neutropenia, for acceleration of neutrophil recovery following haematopoietic stem cell transplantation and in peripheral blood stem cell mobilization

Lenograstim (Granocyte?, Neutrogin?, Myelostim?) is a glycosylated recombinant human granulocyte colony-stimulating factor. This article reviews the pharmacological properties, therapeutic efficacy and tolerability of lenograstim, mainly focusing on its use in chemotherapy-induced neutropenia, acceleration of neutrophil recovery following haematopoietic stem cell transplantation (HSCT), and peripheral blood stem cell (PBSC) mobilization in patients with cancer and healthy donors. In randomized, multicentre trials in patients with solid tumours, lymphoma or multiple myeloma, the durations of chemotherapy-induced neutropenia, hospitalization for infection and intravenous antibacterial therapy were significantly shorter in patients receiving lenograstim prophylaxis than in those receiving placebo. The time to neutrophil recovery was also significantly shorter in patients with acute myeloid leukaemia or acute lymphoblastic leukaemia who received lenograstim than in those who received placebo or no treatment, according to the results of randomized, multicentre trials. In addition, lenograstim prophylaxis facilitated the administration of dose-intense or dose-dense chemotherapy regimens, with improved clinical outcomes seen in some trials. In patients with cancer undergoing HSCT, lenograstim accelerated neutrophil recovery post-HSCT and shortened the duration of hospitalization, according to the results of randomized, multicentre trials. Lenograstim effectively mobilized PBSCs in patients with cancer, demonstrating generally similar efficacy to filgrastim or molgramostim in five randomized trials (although lower dosages of lenograstim than filgrastim were administered in four of the trials). Lenograstim also provided effective PBSC mobilization in healthy donors and was more effective than filgrastim when both drugs were administered at a dosage of 10?μg/kg/day. The efficacy and safety of lenograstim for PBSC mobilization in healthy donors was supported by the results of a prospective, longer-term study involving almost 4000 healthy donors. Lenograstim was generally well tolerated across a variety of treatment settings, including PBSC mobilization in healthy donors, with bone pain being one of the most commonly reported adverse events. In conclusion, lenograstim remains an important option for use in chemotherapy-induced neutropenia, acceleration of neutrophil recovery following HSCT, and PBSC mobilization.     

Filgrastim. A reappraisal of pharmacoeconomic considerations in the prophylaxis and treatment of chemotherapy-induced neutropenia

Neutropenia is a frequent and often dose-limiting complication of chemotherapy and is associated with considerable patient morbidity and mortality. Standard treatment in patients who become febrile includes hospitalisation and empirical antibiotic therapy. Filgrastim is a recombinant human granulocyte colony-stimulating factor (rHuG-CSF). It significantly decreases the incidence of febrile neutropenia in patients receiving standard-dose chemotherapy, and shortens the duration of febrile neutropenia in patients undergoing autologous bone marrow transplantation (BMT) or peripheral blood progenitor cell (PBPC) infusion after myeloablative chemotherapy regimens. These effects are usually associated with a decrease in hospitalisation and antibiotic requirements. The contribution of filgrastim therapy to beneficial effects on other clinically important end-points (e.g. quality of life, tumour relapse rate, and short and long term survival) remains to be accurately determined. Pharmacoeconomic data concerning the use of filgrastim as an adjunct to standard-dose chemotherapy are derived largely from the results of phase III trials. Cost analyses based on hospital charges suggest that the cost of providing filgrastim therapy can be fully recouped if the drug is used as primary prophylaxis in previously untreated patients, for whom the risk of developing febrile neutropenia is at least 40%. Reserving filgrastim for use in patients who have developed febrile neutropenia in a previous chemotherapy cycle may result in further cost savings. However, careful patient selection is required, since potential cost savings will vary depending upon the risk of hospitalisation in the absence of filgrastim treatment. Infusion of filgrastim-mobilised PBPCs is emerging as a preferred strategy in patients receiving myeloablative chemotherapy, and promising results have been obtained from cost analyses. From a pharmacoeconomic viewpoint, future research should be directed towards defining optimum dosage regimens and hence improving the cost-effective use of filgrastim. Data evaluating patient quality of life and treatment preferences would help define the cost utility of filgrastim therapy. In the meantime, available pharmacoeconomic data support the use of filgrastim as an adjunct to chemotherapy in selected clinical situations.     

Cost-benefit analysis of prophylactic granulocyte colony-stimulating factor during CHOP antineoplastic therapy for non-Hodgkin's lymphoma

Several randomised comparative trials have shown that granulocyte colony-stimulating factor (G-CSF) reduces the duration of neutropenia, hospitalisation and intravenous antibacterial use in patients with cancer who are receiving high-dosage antineoplastic therapy. However, one area that has received less attention is the role of G-CSF in standard-dosage antineoplastic regimens. One such treatment that is considered to have a low potential for inducing fever and neutropenia is the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) for non-Hodgkin's lymphoma. We conducted a cost-benefit analysis from a societal perspective in order to estimate the net cost or benefit of prophylactic G-CSF in this patient population. This included direct costs for hospitalisation with antibacterial support, as well as indirect societal costs, such as time off work and antineoplastic therapy delays secondary to neutropenia. The findings were then tested by a comprehensive sensitivity analysis. The administration of G-CSF at a dosage of 5 micrograms/kg/day for 11 doses following CHOP resulted in an overall net cost of $Can1257. In the sensitivity analysis, lowering the G-CSF dosage to 2 micrograms/kg/day generated a net benefit of $Can6564, indicating a situation that was cost saving to society. The results of the current study suggest that the use of G-CSF in patients receiving CHOP antineoplastic therapy produces a situation that is close to achieving cost neutrality. However, low-dosage (2 micrograms/kg/day) G-CSF is an economically attractive treatment strategy because it may result in overall savings to society.     

Granulocytic growth factors and cancer-related neutropenia: limited effects

(1) Cancer chemotherapy often causes haematological complications, in particular neutropenia, which can have grave consequences in terms of the risk of infections (increasing with the degree and duration of neutropenia) and the need for modifications in chemotherapy protocols (longer intervals between cycles or dose reductions). (2) In France, three haematopoietic growth factors are licensed to stimulate leukocyte production: filgrastim (unglycosylated granulocyte colony-stimulating factor (G-CSF)), pegfilgrastim (pegylated filgrastim), and lenograstim (glycosylated G-CSF). (3) The main adverse effects of these three growth factors are joint and bone pain, a flu-like syndrome, and reactions at the injection site. (4) G-CSF has provided disappointing results in primary prevention, and its use is only justified for patients receiving chemotherapy that causes febrile neutropenia in at least 40% of cases: patients with acute leukaemia, elderly patients, and patients with cancer-related neutropenia or poor general status, etc. In these patients, G-CSF reduces the incidence of febrile neutropenia and, possibly, the risk of hospitalisation. A meta-analysis of 11 comparative trials involving about 1500 patients with non Hodgkin's lymphoma showed only a reduction in the incidence of febrile neutropenia and infections. (5) In the prevention of recurrences of neutropenia on continuing chemotherapy, only one trial, involving patients aged over 60 with high-grade non Hodgkin's lymphoma, showed an improvement in survival time with filgrastim (survival rate: 64.3% with filgrastim versus 49% with placebo, after a median follow-up of 40 months). Until these results are confirmed in other clinical trials, reduction in the intensity of chemotherapy (dosage, frequency) is generally recommended. (6) Curative treatment of neutropenia with G-CSF is only warranted for febrile patients with a high risk of severe infections requiring lengthy hospitalisation. Two meta-analyses, one including 8 trials and the other including 13 trials, involving a total of about 1500 patients, only showed a reduction in the length of hospitalisation.     

Recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer: an economic analysis of a randomised, double-blind, placebo-controlled trial

In a blinded retrospective economic evaluation of a double-blind, randomised, placebo-controlled clinical trial, total utilisation and charges for lymphoid cancer patients who received recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or placebo were compared following autologous bone marrow transplantation. The 40 patients enrolled (22 rhGM-CSF, 18 placebo) could have acute lymphoblastic leukaemia, non-Hodgkins lymphoma or Hodgkin's disease, be of any age, and were undergoing autologous bone marrow transplantation in a metropolitan cancer research centre. Main outcome measures consisted of initial hospital lengths of stay (LOS), total and department charges, rehospitalisation rates and charges, and outpatient charges, all inclusive of the first 100 days following bone marrow infusion. The perspective of the study is that of the third party payer. Initial hospitalisation charges were $US54 100 for patients who received rhGM-CSF and $US68 600 for patients who received placebo (p = 0.05). The difference of $US14 500 was 21% less in patients who received rhGM-CSF, mainly due to lower average LOS with rhGM-CSF (24.2 days) compared with placebo (30.8 days). Outpatient charges were $US9500 (rhGM-CSF) and $US6800 (placebo) {p = 0.18}. Total charges, including readmission (10 per group) were $US12 200 lower in the rhGM-CSF group ($US70 300 vs $US82 500, p = 0.19). The use of rhGM-CSF after autologous bone marrow transplantation was shown to result in substantial cost savings during the initial hospitalisation. When comparing total inpatient and outpatient medical charges within the first 100 days following bone marrow infusion, we found no evidence that these savings were negated.     

Economic evaluation of lenograstim for prophylaxis of chemotherapy-induced neutropenia in patients with small cell lung cancer

The impact of lenograstim, recombinant human granulocyte colony-stimulating factor, on healthcare costs was evaluated on the basis of the results of a clinical trial of the drug in patients receiving VICE (vincristine, ifosfamide, carboplatin and etoposide) chemotherapy for small cell lung cancer (SCLC). The use of lenograstim resulted in a significant (p < 0.03) increase in the cumulative chemotherapy dose intensity (125% with lenograstim vs 118% without). Lenograstim was found to have no significant impact on the use of healthcare resources for administration of chemotherapy, chemotherapy-induced neutropenia, and associated infections. The cost of healthcare for the lenograstim group (excluding lenograstim acquisition costs) was 700 pounds higher per patient than that for the group not treated with lenograstim (95% CI -930 pounds to 2300 pounds). The use of lenograstim to intensify the chemotherapy dose is likely to increase the costs of treatment for SCLC. However, any increased costs need to be balanced against the potential cost savings associated with the possible long term benefits resulting from chemotherapy dose intensification.     

Colony-stimulating factors and peripheral blood progenitor cell transplantation. Benefits and costs

High dosage chemo- or radiotherapy followed by the administration of autologous bone marrow-derived stem cells [i.e. autologous bone marrow transplantation (ABMT)] is an established protocol for treating acute myeloid leukaemia and malignant lymphoma. The approach is also under investigation in the treatment of acute lymphocytic leukaemia, multiple myeloma and solid tumours. In all of these diseases, the optimisation of indications, conditioning schemes, stem cell harvest techniques and supportive care with growth factors is subject to continuous preclinical research and clinical phase II and III studies. Recently, the administration of peripheral blood stem cell preparations to cancer patients as rescue therapy after high dosage antitumour therapy has been received with much enthusiasm. At first glance, the technique looks rather easy to perform. The faster recovery of haemopoiesis, compared with ABMT, leads to shorter durations of hospitalisation. Moreover, in most studies, peripheral blood progenitor cell transplantation (PBPCT) resulted in fewer septic episodes, fewer intensive care admissions, fewer red blood cell and platelet transfusions, reduced use of anti-infectives and parenteral nutrition, and reduced hospital costs compared with ABMT. The overall conclusion is that the treatment costs of PBPCT are 15 to 30% lower than the treatment costs of ABMT. However, a formal comparison between PBPCT and ABMT, assessing the differences in toxicity, costs and quality of life, is still awaited.     

Cost effectiveness of cephalosporin monotherapy and aminoglycoside/ureidopenicillin combination therapy. For the treatment of febrile episodes in neutropenic patients

OBJECTIVE: To assess the relative cost effectiveness of cephalosporin monotherapy options and aminoglycoside/ureidopenicillin combination therapy for the treatment of febrile episodes in adult patients with neutropenia. DESIGN AND SETTING: This was a retrospective cost-effectiveness analysis conducted from the institutional perspective. METHODS: The analysis was based on 741 febrile episodes in adult patients with neutropenia enrolled in 5 randomised trials: 3 comparing monotherapy with ceftazidime or cefepime, and 2 comparing cefepime monotherapy versus aminoglycoside/ureidopenicillin combination therapy. Resource utilisation included costs for study antibacterials, treatment of adverse effects and failures, and hospitalisation. The primary end-point was the overall cost of treatment per patient. Cost-effectiveness ratios were also analysed. RESULTS: No significant differences in clinical success rates were detected. Median per-patient costs in the monotherapy comparisons were $US7849 for cefepime and $US7788 for ceftazidime [1997 values; not significantly different (NS)]. Corresponding costs for the monotherapy versus combination therapy comparisons were $US9780 for cefepime and $US10 159 for gentamicin/ureidopenicillin (NS). Despite a higher acquisition cost for cefepime, there were no statistically significant differences in cost effectiveness compared with either ceftazidime monotherapy or gentamicin/ureidopenicillin combination therapy. Sensitivity analyses revealed that monotherapy can be cost effective compared with combination therapy in many situations. CONCLUSION: There were no economic differences between the 3 regimens tested. Therefore drug cost should not be a deciding factor when choosing antibacterial therapy for the treatment of febrile episodes in adult patients with neutropenia.     

Overview of the lenograstim pharmacoeconomics programme

Lenograstim is a recombinant colony-stimulating factor that has been shown to be a useful adjunctive agent in cancer chemotherapy. Clinical trials have demonstrated the efficacy of lenograstim in correcting chemotherapy-induced neutropenia and associated complications in inflammatory breast cancer and non-Hodgkin's lymphoma, and in facilitating dose intensification of chemotherapy in small cell lung cancer. To meet increasing demands for economic data on new drug entities, a lenograstim pharmacoeconomics programme was established. This programme involved prospective economic evaluations of lenograstim that were undertaken as part of phase III randomised clinical trials by a combined German/Italian health-economics team (inflammatory breast cancer), a French team (non-Hodgkin's lymphoma), and a team from the UK (small cell lung cancer).     

Lenograstim: an update of its pharmacological properties and use in chemotherapy-induced neutropenia and related clinical settings

Lenograstim is the glycosylated recombinant form of human granulocyte colony stimulating factor. The drug is used to reduce the risk of life-threatening infection in patients with neutropenia, particularly after cytotoxic chemotherapy. Lenograstim accelerates neutrophil recovery significantly after chemotherapy, with beneficial effects on clinical end-points such as incidence of laboratory-confirmed infection and length of hospital stay. Chemotherapy dose intensity has also been increased in patients receiving lenograstim, notably those with breast or small cell lung cancer, although improvements in tumour response and survival have not been demonstrated. Lenograstim also assists neutrophil recovery in patients undergoing bone marrow transplantation, and stimulates the production of peripheral blood stem cells (PBSCs) for autologous transfusion after aggressive chemotherapy. Lenograstim also mobilises CD34+ cells more efficiently in unit dose terms than filgrastim and has been used successfully to mobilise PBSCs from healthy donors for allogeneic transplantation. Randomised trials have shown increases in rates of disease remission after lenograstim therapy in patients with acute myeloid leukaemia, with no evidence of stimulation of malignant blasts. The drug has also shown potential in the mobilisation of nonmalignant PBSCs for autotransplantation in patients with chronic myeloid leukaemia. Other studies show efficacy of lenograstim in patients with acute lymphoblastic leukaemia, aplastic anaemia, in children with severe chronic neutropenia and in the reversal of neutropenia related to antiviral therapy in patients with AIDS, although data are not extensive. Cost analyses of lenograstim have been carried out from a hospital perspective, although results have been inconclusive. Cost-effectiveness or cost-benefit data are lacking at present. Lenograstim is well tolerated, with bone pain and injection site reactions being reported most frequently in clinical trials. Conclusions: Lenograstim has been confirmed as a valuable adjunct to minimise the haematological toxicity of myelosuppressive chemotherapy in patients with malignant disease. The drug also enhances neutrophil recovery in patients undergoing stem cell rescue, and assists PBSC mobilisation. Data indicate clinical benefit with lenograstim in myeloid disorders, with no evidence of malignant blast cell proliferation. Further studies are required to assess more fully the pharmacoeconomic implications of the use of lenograstim and other recombinant growth factors, to provide more data on the efficacy of the drug in the management of disease-related neutropenia, and to clarify fully its position relative to filgrastim.     

Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF): an appraisal of its pharmacoeconomic status in neutropenia associated with chemotherapy and autologous bone marrow transplant

Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) expedites neutrophil recovery in cancer patients receiving chemotherapy with or without autologous bone marrow transplant (ABMT). The limited cost analyses available in patients undergoing ABMT support a cost reduction of about 25 to 35% with rGM-CSF therapy, relative to placebo, generated primarily by decreases of 20 to 30% in hospitalisation costs reflecting reductions in length of hospitalisation. Results of 1 trial show equivalent cost savings of 40% versus placebo with either rGM-CSF or recombinant granulocyte colony-stimulating factor (rG-CSF) in patients with chemotherapy-induced febrile neutropenia. Whether reduced infection rates seen with rGM-CSF may lessen costs of antimicrobial therapy is undetermined; however, a 16% decrease in this cost factor was reported in 1 evaluation of high dose chemotherapy with ABMT. No analyses have assessed the cost effectiveness of rGM-CSF as prophylaxis in patients receiving chemotherapy. Survival rates have increased in patients treated with rGM-CSF after bone marrow graft failure. In contrast, with the exception of one small trial, improvements in mortality or relapse rates have not occurred with rGM-CSF used prophylactically with chemotherapy, despite favourable effects on neutrophil recovery and facilitation of dose-intensified chemotherapy regimens. Similarly, survival has not increased in patients undergoing ABMT. The long term economic impact of rGM-CSF in these indications is thus unknown. Other factors predicted to produce modest cost savings include possible reductions in expenditure related to treating mucositis, and lowered transfusion requirements in some patients. Whether rGM-CSF may provide benefits in other areas that can be expressed in economic terms, such as quality of life, also remains to be established. On the whole, rGM-CSF has a good tolerability profile, obviating the need for costly monitoring procedures. Like other expensive biotechnology products, its cost effectiveness will be aided by implementation of appropriate prescribing techniques and protocols to minimise wastage. Thus, at present rGM-CSF therapy appears to offer a means of reducing hospitalisation costs, and therefore a substantial component of treatment expenditure, in patients undergoing ABMT or with chemotherapy-induced febrile neutropenia.     

Pharmacoeconomic evaluation of lenograstim. Conclusions and future directions

To evaluate the safety and efficacy of lenograstim, a new recombinant human granulocyte colony-stimulating factor (rHuG-CSF), as an adjunct to cancer chemotherapy, 3 phase III randomised clinical trials were recently conducted in Europe in patients with inflammatory breast cancer, non-Hodgkin's lymphoma, and small cell lung cancer. To explore the economic implications of lenograstim therapy, a multinational pharmacoeconomics programme was undertaken using data collected during these clinical trials. This programme consisted of concurrent prospective economic evaluations undertaken by study teams in France (non-Hodgkin's lymphoma), Germany and Italy (a combined evaluation in inflammatory breast cancer) and the UK (small cell lung cancer). In these studies, attention was focused on the direct costs of medical care-principally the costs of cancer chemotherapy as well as its associated morbidity. In 2 of the pharmacoeconomic evaluations (i.e. the French, German/Italian), lenograstim was found to generate cost savings as a result of reductions in morbidity associated with chemotherapy. However, the cost of lenograstim therapy would be likely to exceed these savings, leading to an overall increase in the costs of cancer treatment. Whether the use of lenograstim is cost-effective will therefore largely depend on its impact on patient survival and quality of life, and current practical use. These issues are the focus of additional clinical studies currently underway. In addition, new research is focusing on the clinical benefits of lenograstim in other areas of oncology and haematology. Further pharmacoeconomic studies in these areas are also warranted.     

Comparison of lenograstim and filgrastim on haematological effects after autologous peripheral blood stem cell transplantation with high-dose chemotherapy

OBJECTIVE: To compare the efficacy of lenograstim and filgrastim on haematological recovery following an autologous peripheral blood stem cell transplantation (PBSCT) with high-dose chemotherapy. METHODS: A retrospective case-controlled study. RESULTS: Absolute neutrophil count (ANC) recovery above 0.5 x 10(9)/l and white blood cell (WBC) recovery above 4 x 10(9)/l for 3 consecutive days was achieved earlier with filgrastim than with lenograstim ((13.2 +/- 8.0 vs 19.0 +/- 10.0 days, p = 0.004), (16.9 +/- 9.7 vs 29.9 +/- 16.6 days, p = 0.001), respectively). The platelet recovery above 20 x 10(9)/l was also achieved earlier with filgrastim than with lenograstim (19.5 +/- 11.6 vs 27.2 +/- 13.8 days, p = 0.006). Furthermore, filgrastim-treated patients received fewer days of granulocyte colony simulating factor (G-CSF) administration (12.5 +/- 7.0 vs 18.6 +/- 8.5 days, p = 0.001) and spent less time in hospital (23.7 +/- 10.9 vs 32.0 +/- 17.6 days, p = 0.009). Duration of antibiotic administration was also significantly shorter in the filgrastim group (13.6 +/- 7.6 vs 29.1 +/- 19.8 days, p = 0.001). CONCLUSION: In patients undergoing PBSCT following high-dose chemotherapy, filgrastim significantly reduced the duration of neutropenia, thrombocytopenia and days of G-CSF administration, and led to earlier hospital discharge compared with lenograstim.     

Mobilization of peripheral blood stem cells by granulocyte-colony stimulating factors: comparison of a standard dose of glycosylated and mutated granulocyte-colony stimulating factor in non-Hodgkin's lymphoma patients following CHOP therapy

The effects of granulocyte-colony stimulating factor (G-CSF) have been studied in several clinical settings. G-CSFs are widely used to stimulate the production of granulocytes and are well known to mobilize peripheral blood stem cells (PBSCs). However, very few studies have examined differences among G-CSFs. The aim of this study was to compare the mobilization of PBSCs induced by a standard dose of two G-CSFs following biweekly cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) therapy. Using a standard dose of G-CSF, we conducted a randomized, crossover trial that compared the efficacy of two kinds of G-CSF, glycosylated [lenograstim (2 micrograms/kg)] and mutated [nartograstim (1 microgram/kg)], on PBSC mobilization in 10 patients with non-Hodgkin's lymphoma after biweekly CHOP chemotherapy. Lenograstim (2 micrograms/kg) was more effective in shortening the duration of neutropenia than nartograstim (1 microgram/kg) (3.8 days vs. 5.0 days, p < 0.05, the number of days for the neutrophil count to reach 5 x 10(9)/l from nadir). The number of CD34+ cells and granulocyte-macrophage colony forming units (GM-CFU) was higher for lenograstim but no statistically significant difference between the two groups was found. Glycosylated G-CSF is more effective than mutated G-CSF in shortening the duration of neutropenia. As for the mobilization of CD34+ cells and the number of CFU-GM, there was a tendency to increase in the lenograstim group but no statistically significant differences were found.     

Economic evaluation of lenograstim (glycosylated rHuG-CSF) in the treatment of inflammatory breast cancer for Germany and Italy

Data from a French placebo-controlled double-blind trial in 120 female patients treated with high dose fluorouracil, epirubicin and cyclophosphamide (HD-FEC) chemotherapy for inflammatory breast cancer were used to assess the economic impact of adjunctive lenograstim therapy. The analysis compared direct costs of treatment, with or without lenograstim, with reference to the Social Security (Germany) or to the National Health Service (Italy). Resource utilisation differed between the 2 treatment groups. The lenograstim group reported 32% fewer antibiotic therapy days (9.8 days vs 14.6; p = 0.01) and 24% fewer inpatient days for any reason other than chemotherapy (7.4 'excess' days vs 9.8). By reducing infection-related morbidity associated with a high dose chemotherapy regimen, lenograstim decreased treatment costs by DM 1794 and ItL 1.2 million, excluding the cost of lenograstim itself. Since lenograstim patients reported fewer chemotherapy delays (16.4 vs 30.5%) and, hence, benefited from 1.2 (p = 0.04) more chemotherapy days, the related cost was DM 1519 and ItL 0.9 million higher than for the placebo group. This cost difference would be expected to be smaller if the placebo group patients had been followed until completion of their full chemotherapy regimen. Assuming that the costs of chemotherapy were the same for both groups, the direct cost saving for the lenograstim group would be 30% in Germany and 34% in Italy.     

Treatment costs and quality of life with granulocyte-macrophage colony-stimulating factor in patients with antineoplastic therapy-related febrile neutropenia. Results of a randomised placebo-controlled trial

This study examined the costs of treatment of, and quality of life in, patients with antineoplastic therapy-induced neutropenic fever who were treated with antibacterials, with or without granulocyte-macrophage colony-stimulating factor (GM-CSF). Patients with haematological malignancies (n = 47) or solid tumours (n = 87) who had severe neutropenia (neutrophil count < 0.5 x 10(9)/L) and fever (> 38.5 degrees C once, or > 38 degrees C twice, in a 12-hour observation period) were randomised to receive subcutaneous GM-CSF 5 micrograms/kg/day (n = 65) or placebo (n = 69) in conjunction with broad-spectrum antibacterials. GM-CSF enhanced neutrophil recovery compared with placebo. Median neutrophil counts at day 4 were 2.9 (range 0 to 25) x 10(9)/L in the GM-CSF arm and 1.3 (range 0 to 9) x 10(9)/L in the placebo group (p < 0.001). No significant difference was observed with regard to median days with neutrophil count < or = 1.0 x 10(9)/L or in time to resolution of fever. Quality-of-life scores in 90 patients demonstrated significant differences in favour of the placebo group. The results for the oncology and haematology patients were similar to the results for the total group. Patients in the GM-CSF and placebo groups had a mean hospital stay of 7.25 and 8.33 days, respectively. Hospital costs were higher for the GM-CSF-treated patients when GM-CSF was included in the price [mean costs: GM-CSF arm $US 5177 vs placebo arm $US 4178 (p < 0.05; 1992 values)]. The haematology patients stayed longer in hospital than the oncology patients, resulting in higher total costs for the former group. These results indicate that GM-CSF does not affect the number of days required for resolution of fever of the hospitalisation period for this patient group, and does not provide a cost-effective contribution to the treatment of these patients. Sensitivity analyses indicate that GM-CSF would produce savings if the duration of hospitalisation with GM-CSF was < or = 76.5% of that in the placebo group.     

Phase II trial of intravenous melphalan in advanced colorectal carcinoma

SummaryBackground Relatively few studies have examined the activity of alkylating agents in the treatment of advanced colorectal adenocarcinoma. Recent reports have suggested possible therapeutic activity for high-dose intravenous melphalan administered with autologous bone marrow transplantation (BMT) support. We conducted a phase II study to determine the efficacy of administering intravenous melphalan at doses that do not require BMT support in patients with advanced colorectal adenocarcinoma.Patients and methods Fifteen patients with histologically proven, bidimensionally measurable disease were treated. The starting dose of melphalan was 30 mg/m², with dose escalation permitted.Results No objective responses were observed. Toxic effects were primarily reversible granulocytopenia and thrombocytopenia. There were no treatmentassociated deaths.Conclusion Melphalan's lack of efficacy at the doses administered does not disprove the steep chemotherapy dose-response relationship postulated for many solid tumors. However, we feel that it is unlikely that repetitive courses of high dose melphalan with autologous BMT support will be a practical approach to the management of advanced colorectal adenocarcinoma.     

Incremental cost-effectiveness ratio of alteplase in patients with acute myocardial infarction in the French setting

On the basis of data collected from general hospital centres in France on 704 patients initially presenting with acute myocardial infarction, the mean 1-year cost of treatment was calculated to be 52,160 French francs (F) per patient (1994 values). This was independent of whether the patient received thrombolysis, and included all costs associated with initial hospitalisation including a stay in intensive care, cardiology or medical units, as well as rehospitalisations, revascularisation procedures and any drugs prescribed. When only those patients who survived the initial hospitalisation were considered, the mean cost of treatment was F58,184 per patient. Among patients who received thrombolysis during their initial hospitalisation, the respective mean 1-year costs were F74,684 per patient for those treated with alteplase and F64,866 per patient for those treated with streptokinase (p = 0.09). This nonsignificant difference can be explained by the higher cost of alteplase relative to that of streptokinase, the lower mortality rate associated with alteplase during the initial hospitalisation period (9.2% versus 10.6%) and the difference in the percentage of additional revascularisations required in the 2 treatment groups (32.8% versus 42.3%). Combining the pharmacoeconomic data collected in the French general hospital setting with incremental patient survival data stemming from the Global Utilisation of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial showed that the incremental cost-effectiveness ratio of alteplase versus streptokinase amounted to F70128 per life-year saved for the total group, and F52035 per life-year saved for those patients who survived the initial period of hospitalisation.     

Effect of clinical characteristics on neutropenia-related inpatient costs among newly diagnosed non-Hodgkin's lymphoma cases during first-course chemotherapy

STUDY OBJECTIVE: To estimate the costs of hospitalization for neutropenia among chemotherapy-treated patients with newly diagnosed non-Hodgkin's lymphoma and to assess baseline patient factors associated with these costs. DESIGN: Retrospective cohort study. DATA SOURCE: Linked Surveillance, Epidemiology, and End Results Program-Healthcare Cost and Utilization Project databases for Iowa from 1993-1998. PATIENTS: Patients with newly diagnosed non-Hodgkin's lymphoma who received all inpatient care at Iowa hospitals during their first course of chemotherapy. MEASUREMENTS AND MAIN RESULTS: Neutropenia-related hospitalization costs were estimated from discharge abstracts found within the earliest of the following: 6 months after the diagnosis month, the date of bone marrow transplantation, or date of death. We performed univariate tests of differences in neutropenia-related hospitalization costs in all patients in the sample, as well as tests for neutropenia-related hospitalization costs, length-of-stay, and cost/inpatient day for patients with at least one hospitalization for neutropenia. We modeled total inpatient charges over the period for patients with at least one neutropenia-related hospitalization (multiple regression). A total of 1636 patients with non-Hodgkin's lymphoma had chemotherapy in Iowa and met inclusion criteria; of these, 316 had at least one hospitalization for neutropenia. The 316 patients had 418 stays. Patients with advanced stage (vs limited stage), previous anemia (vs no anemia), positive Charlson comorbidity score (vs score of 0), and diffuse large cell histology (vs follicular) had higher mean neutropenia-related hospitalization cost/patient with non-Hodgkin's lymphoma (p<0.05). Among those with neutropenia-related hospitalizations, a longer length of stay was associated with nonfollicular histologies, previous anemia, and positive Charlson score (p<0.05). CONCLUSION: When estimating expected payments for neutropenia-related hospitalization in patients with non-Hodgkin's lymphoma, payers need to be aware of the distribution of clinical characteristics in these patients.