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.     

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.     

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.     

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

SUMMARY

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?×?10⁹?l^?1 and white blood cell (WBC) recovery above 4?×?10⁹?l^?1 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 10⁹/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.     

Lamivudine for the prevention of hepatitis B virus reactivation after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for patients with advanced or relapsed non-Hodgkin's lymphoma single institution experience

Objective: Hepatitis B virus (HBV) reactivation is a well-known complication in cancer patients receiving cytotoxic chemotherapy, resulting in varying degrees of liver damage. The objective of this study was to investigate the efficacy of lamivudine for the prevention of HBV reactivation in non-Hodgkin's lymphoma (NHL) patients undergoing high-dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT). Research design and methods: Thirty-two patients with NHL who were HBV surface antigen (HBsAg)-positive were enrolled in this pilot study. They were divided into two groups: 20 patients received prophylactic oral lamivudine 100 mg/day before, and until at least 6 months after transplantation. The historical control group comprised 12 patients who received high-dose chemotherapy and AHSCT without lamivudine. The incidence and severity of hepatitis due to HBV reactivation, as well as other adverse clinical outcomes, were compared between the two groups. Results: Most baseline clinical characteristics were similar in the two groups, except for HBV e-antigen (HBeAg)-positive status (85% in the lamivudine group vs 33.3% in the control group, p = 0.006) and the type of AHSCT. There was a lower incidence of hepatitis due to HBV reactivation in the lamivudine group than in the control group (10 vs 50%, p = 0.030), less severe hepatitis (0 vs 25%, p = 0.009), and lower mortality (0 vs 25%, p = 0.236). An HBV variant with tyrosine methionine aspartate aspartate (YMDD) mutation was detected in one patient in the lamivudine group (5%) after administration of lamivudine for 9 months. No significant adverse events were associated with the use of prophylactic lamivudine, and hematopoietic reconstitution was not affected by the intervention. Conclusions: Prophylactic lamivudine may reduce the incidence and severity of chemotherapy-related HBV reactivation and hepatitis-related mortality in HBsAg-positive NHL patients receiving high-dose chemotherapy and AHSCT. Additional randomized, multicenter trials are warranted.     

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.     

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.     

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.     

Effect of lenograstim on the cost of autologous bone marrow transplantation. A preliminary communication

High dose chemotherapy and autologous bone marrow transplantation (BMT) can produce prolonged remission in patients with malignant lymphoma or solid tumours. However, neutropenia is a serious complication of treatment in patients with these diseases. In this study, we investigated the costs and effects of using lenograstim, a recombinant human granulocyte colony-stimulating factor, to treat neutropenia in 16 patients with lymphoma or solid tumours. The cost of lenograstim was not included in the calculations. The duration of neutropenia and hospitalisation were both lower in patients who received lenograstim compared with no treatment. The mean cost of autologous BMT was FF142,000 in patients who received lenograstim, compared with FF166,000 in patients who did not. Savings were largely attributable to decreased expenditure on hospitalisation in the lenograstim-treated group. The cost of 14 days' treatment with lenograstim was estimated at FF10,500, based on a daily dosage of 150 micrograms/m2/day.     

重型颅脑损伤医院感染经济损失的病例对照研究

目的 了解重型颅脑损伤患者医院感染所造成的经济损失。方法 对感染组和对照组的医疗费用和住院天数进行病例对照分析。结果 重型顷脑损伤医院感染组平均每例的住院天数比对照组增加34d，住院总费用增加42035．7元，两组差异有统计学意义（P〈0．001）；感染组的住院分类费用也明显高于对照组（P〈0．01）。结论 医院感染所造成的直接经济损失是巨大的。因此要重点监测重型颅脑损伤医院感染高危患者，以便及时采取有效的措施降低医院感染率，从而有效降低医院感染对患者造成的经济损失，节约卫生资源。     

Omeprazole or ranitidine plus metoclopramide for patients with severe erosive oesophagitis. A cost-effectiveness analysis

The objective of this study was to evaluate the clinical and economic effects of 2 clinical strategies for treating severe (grade II and above) erosive oesophagitis or poorly responsive gastro-oesophageal reflux disease. A single-blind, randomised controlled trial of up to 8 weeks' duration was undertaken comparing omeprazole with ranitidine plus metoclopramide in patients with severe and symptomatic erosive oesophagitis (endoscopic grade II and above). Two cost-effectiveness ratios were calculated: cost per healed patient and cost per symptom-free day. The study perspective was that of the payer or insurer of medical care. Healing rates were significantly higher among omeprazole-treated patients than among those who received ranitidine/metoclopramide at 4 weeks (68.5% vs 30.4%; p < 0.01) and overall (81.5% vs 45.7%; p < 0.01). Overall, mean gastrointestinal-related direct medical costs per healed patient were lower for the omeprazole group ($US189.60) than for the ranitidine/metoclopramide group ($US319.28). The incremental cost of an additional cure with omeprazole compared with ranitidine/metoclopramide was $US24.05. The overall average cost per symptom-free day was lower in the omeprazole group ($US7.88) than in the ranitidine/metoclopramide group ($US10.81). The incremental cost to obtain an additional symptom-free day with omeprazole, compared with ranitidine/metoclopramide, was $US1.41. In conclusion, superior efficacy at comparable cost is achieved by omeprazole compared with ranitidine/metoclopramide in the treatment of patients with severe erosive oesophagitis.     

非霍奇金淋巴瘤患者乙型肝炎病毒感染状况与预后的关系

目的:探讨非霍奇金淋巴瘤(NHL)患者乙型肝炎病毒(HBV)感染状况及预后的关系。方法:回顾性分析67例非霍奇金淋巴瘤患者HBV病毒表面抗原(HB sA g)的表达、肝功能变化及拉米夫定的作用,同时与67例非原发性肝癌实体瘤患者及67例普通人群做对比。结果:67例NHL患者HB sA g阳性率为23.9%,明显高于本地区普通人群(9.0%)及非原发性肝癌实体瘤患者(10.4%);HB sA g阳性的NHL组中,化疗后肝损害发生率(68.8%)与HB sA g阴性患者发生率(29.4%)之间差异有显著性(P<0.05);拉米夫定在预防病毒复活时起到重要作用。结论:NHL患者HB sA g阳性率高于本地非原发性肝癌实体瘤患者(其他肿瘤组)及普通人群组,拉米夫定可在一定程度上预防HBV的再激活;HBV感染者在化疗时应加强保肝并密切监测肝功能的变化。     

Resource utilisation and cost analysis of memantine in patients with moderate to severe Alzheimer's disease

BACKGROUND: Alzheimer's disease (AD) is a devastating illness that causes enormous emotional stress to affected families and is associated with substantial medical and nonmedical costs. OBJECTIVE: To determine the effects of 28 weeks of memantine treatment for patients with AD on resource utilisation and costs. STUDY DESIGN AND METHODS: Multicentre, prospective, double-blind, randomised, placebo-controlled clinical trial performed in the US. The Wilcoxon-Mann-Whitney test was used to examine the resource utilisation variables and logistic regression models were used for multivariate resource utilisation analyses. Analysis of covariance (ANCOVA) models (log and non-log) were computed to examine costs from a societal perspective. All costs were calculated in 1999 US dollars. Study population: Outpatients with moderate to severe AD. Overall, 252 patients received randomised treatment, and 166 patients (placebo n = 76, memantine n = 90) formed the treated-per-protocol (TPP) subset for the health economic analyses, on which the main cost analysis was based. MAIN OUTCOME MEASURE: Resource Utilisation in Dementia (RUD) scale, measuring patient and caregiver resource utilisation, and various sources for cost calculations. RESULTS: Controlling for baseline differences between the groups, significantly less caregiver time was needed for patients receiving memantine than for those receiving placebo (difference 51.5 hours per month; 95% CI -95.27, -7.17; p = 0.02). Analysis of residential status also favoured memantine: time to institutionalisation (p = 0.052) and institutionalisation at week 28 (p = 0.04 with the chi-square test). Total costs from a societal perspective were lower in the memantine group (difference dollars US 1089.74/month [non-overlapping 95% CI for treatment difference -1954.90, -224.58]; p = 0.01). The main differences between the groups were total caregiver costs (dollars US-823.77/month; p = 0.03) and direct nonmedical costs (dollars US-430.84/month; p = 0.07) favouring memantine treatment. Patient direct medical costs were higher in the memantine group (p < 0.01), mainly due to the cost of memantine. CONCLUSION: Resource utilisation and total health costs were lower in the memantine group than the placebo group. The results suggest that memantine treatment of patients with moderate to severe AD is cost saving from a societal perspective.     

卡培他滨治疗消化道恶性肿瘤的药物经济学评价

目的 :提供卡培他滨治疗消化道恶性肿瘤的药物经济学评价依据。方法 :比较卡培他滨单药口服和5 -氟尿嘧啶 +亚叶酸 +奥沙利铂 (FOLFOX4)方案治疗消化道恶性肿瘤的疗效、不良反应、直接医疗费用和间接费用 ,并以最小成本分析法进行药物经济学评价。结果 :卡培他滨组与FOLFOX4组疗效相近 ,分别为30. 3 %、38. 9 % (P>0. 05 ,X2=0. 45) ,病灶稳定率分别为42 5 %、32. 4 % ,而每个疗程住院天数卡培他滨组明显少于FOLFOX4组 ,分别为8 5天、25. 3天 (P=0.000) ,且每个疗程医疗总费用卡培他滨组也明显低于FOLFOX4组 ,分别为5941 7元、13304. 6元 (P=0 001)。经费用结构分析显示 ,与卡培他滨组比较 ,FOLFOX4组的直接医疗费用和间接费用增加都非常明显 (P=0.001) ;不良反应发生率卡培他滨组也较低。结论 :从药物经济学角度看 ,在消化道恶性肿瘤的治疗中卡培他滨口服方案优于FOLFOX4方案。     

Epoetin Theta in Anaemic Cancer Patients Receiving Platinum-Based Chemotherapy: A Randomised Controlled Trial

INTRODUCTION: Recombinant human erythropoietin (r-HuEPO) is used to treat symptomatic anaemia due to chemotherapy. A new r-HuEPO, Epoetin theta (Eporatio?), was investigated and compared to placebo and Epoetin beta in a randomised, double-blind clinical trial in adult cancer patients receiving platinum-based chemotherapy, using a fixed weekly starting dose of 20,000 IU Epoetin theta. The primary efficacy endpoint was the responder rate (complete Hb response, Hb increase ≥ 2 g/dL). RESEARCH DESIGN AND METHODS: 223 patients were randomised to s.c. treatment for 12 weeks with either Epoetin theta (n = 76) once per week, Epoetin beta (n = 73) three times per week or placebo (n = 74). The starting dose was 20,000 IU once weekly Epoetin theta or 450 IU/kg(BW) per week Epoetin beta administered in 3 equal weekly doses. RESULTS: In the Epoetin theta group were significantly more responders than in the placebo group (65.8 vs. 20.3%, P < 0.0001). Epoetin beta was also more effective than placebo (71.2 vs. 20.3%, P < 0.0001). The mean weekly dose at the time of complete Hb response was lower in the Epoetin theta group (30,000 IU) than in the Epoetin beta group (42,230 IU). Epoetin theta was clearly more effective than placebo. CONCLUSION: This small study showed, that Epoetin theta is a safe and effective treatment of symptomatic anaemia due to platinum-based chemotherapy in cancer patients.     

Efficacy and safety of a fixed combination phytomedicine in the treatment of the common cold (acute viral respiratory tract infection): results of a randomised, double blind, placebo controlled, multicentre study

OBJECTIVE: The common cold (acute viral respiratory tract infection) is one of the most frequent diseases in man, world-wide. Clinically relevant efficacy should include early improvement of all symptoms. Results of a clinical trial of a commercially available fixed combination herbal remedy (Radix echinaceae, Radix baptisiae, Herba thujae) are reported here. The aim of this study was to verify clinical efficacy shown in recent studies under (i) good clinical practice (GCP) quality assurance and (ii) common situations at family doctors. METHODS: Patients attending one of 15 study centres (practitioners) as a result of an acute common cold were randomised to the double-blind placebo-controlled study. Three tablets of study medication were applied t.i.d. for 7 to 9 days. Patients daily documented the intensity of 18 cold symptoms, as well as the cold overall, using a 10-point scale and estimated their general well-being using the Welzel-Kohnen colour scales. Additionally, the severity of illness was assessed by the physician on days 4 and 8 (CGI-1). The main and confirmatory outcome measure was expressed as a total efficacy value. This was gauged from the z-standardised AUC values of the primary endpoints (rhinitis score, bronchitis score, CGI-1 and general well-being). Adverse events, overall tolerability, vital signs and laboratory parameters were documented. RESULTS: 263 patients were included. For safety analysis, all patients were used. 259 patients were evaluable for primary efficacy analysis (ITT). Results were confirmed analysing only the 238 valid cases (VCs). The primary efficacy parameters showed the superiority of the herbal remedy over placebo (p < 0.05). Effect size was 20.6% of the standard deviation (90% CI: 0.04-41.1%; ITT) and 23.1% (1.7-44.5%; VC). In relation to the general well-being, the effect size was 33.9% of the standard deviation (12.5-55.3%; VC). Patients who suffered from at least moderate symptom intensity at baseline showed response rates (at least 50% improvement of the global score, day 5) of 55.3% in the herbal remedy group and 27.3% in the placebo group (p = 0.017; NNT = 3.5). In the subgroup of patients who started therapy at an early phase of their cold, the efficacy of the herbal remedy was most prominent (p = 0.014 for the primary efficacy parameter). The therapeutic benefit of the herbal remedy had already occurred on day 2 and reached significance (p < 0.05) on day 4, and continued until the end of the treatment in the totdl score of symptoms, bronchitis score and rhinitis score, as well as in the patients' overall rating of the cold intensity. At that time, equal levels of improvement were reached three days earlier in the verum group than in the placebo group. In 26 patients receiving the herbal remedy and 23 patients receiving placebo, adverse events were reported. Adverse drug reactions were suspected in two patients in the verum group and in four patients in the placebo group. Serious adverse events did not occur. CONCLUSIONS: This study shows that the herbal remedy is effective and safe. The therapeutic benefit consists of a rapid onset of improvement of cold symptoms. If patients with colds are able to start the application of the herbal remedy as soon as practical after the occurrence of the initial symptoms, the benefit would be expected to increase (e.g. self-medication).     

First-step treatment of mild to moderate uncomplicated essential hypertension by a new calcium antagonist: nicardipine

Nicardipine, a new calcium antagonist, was tested in a 14-week double-blind trial including 15 outpatients with uncomplicated essential hypertension. They were randomly assigned to nicardipine (20-30 mg three times daily) or placebo as first-step treatment. When necessary but always after a minimum of 4 weeks, pindolol (15 mg/day) was combined with nicardipine or placebo. At the end of step 1 (85 +/- 6 days with nicardipine vs. 58 +/- 6 days with placebo, p less than 0.01), nicardipine induced larger drops in supine systolic and diastolic blood pressure (SBP and DBP) than the placebo (21 +/- 2.5 vs 1.4 +/- 3 mm Hg, p less than 0.001, and 13 +/- 2 vs. 3.5 +/- 1.5 mm Hg, p less than 0.001, respectively). In the nicardipine group (n = 57), 53% of patients had controlled blood pressure (SBP less than 160 mm Hg and DBP less than 95 mm Hg) versus 17% in the placebo group (n = 47), p less than 0.001. There was no significant correlation between the decrease in blood pressure and the age of patients. The most common side effects in the nicardipine group were flushes (12%), headache (8%), ankle edema (5%), and asthenia (4%). When blood pressure was not brought under control and pindolol was prescribed as the second-step treatment, the nicardipine group (n = 52) displayed larger drops in SBP and DBP than the placebo group (n = 40) (27 +/- 5 vs. 15 +/- 3 mm Hg, p less than 0.01, and 18 +/- 1 vs. 9 +/- 2 mm Hg, p less than 0.001, respectively). These results show that a calcium antagonist is useful for first-step treatment of hypertension.     

Epoetin Theta with a New Dosing Schedule in Anaemic Cancer Patients Receiving Nonplatinum-Based Chemotherapy: A Randomised Controlled Trial

INTRODUCTION: Recombinant human erythropoietin (r-HuEPO) is used to treat symptomatic anaemia due to chemotherapy. A new r-HuEPO, Epoetin theta (Eporatio?), was investigated and compared to placebo in a randomised, double-blind clinical trial in adult cancer patients receiving nonplatinum-based chemotherapy. The primary efficacy endpoint was the responder rate (complete haemoglobin (Hb) response, i.e., Hb increase ≥2 g/dl) without the benefit of a transfusion within the previous 4 weeks. RESEARCH DESIGN AND METHODS: 186 patients were randomised to s.c. treatment for 12 weeks with either Epoetin theta (N = 95) or placebo (N = 91). The starting dose was 20,000 IU once weekly Epoetin theta or placebo. RESULTS: The incidence of complete Hb responders was significantly higher in the Epoetin theta group than in the placebo group (72.6 vs. 25.3%, P < 0.0001). More patients in the placebo group than in the Epoetin theta group received blood transfusions after randomisation (23 patients, 25.3% vs. 13 patients, 13.7%, P = 0.0277). The majority of patients with a complete Hb response had 20,000 IU/week as their maximum dose prior to response, indicating that a dose of 20,000 IU is an appropriate starting dose. The overall frequencies of adverse events (AEs) were similar in both treatment groups. Hypertension was the only AE that was more frequent in the Epoetin theta group compared to the placebo group (8.4 vs. 1.1%). CONCLUSIONS: Epoetin theta showed a superior efficacy to placebo in terms of complete Hb response without blood transfusion within the previous 4 weeks. Treatment with Epoetin theta resulted in a statistically significant increase in mean haemoglobin levels compared to placebo. The overall frequencies of adverse events were similar in both treatment groups.     

吡喃阿霉素米托蒽醌治疗非霍奇金淋巴瘤

目的 观察以吡喃阿霉素为主的CTOP方案治疗非霍奇金淋巴瘤的疗效，并与以米托蒽醌为主的CMOP方案进行比较。方法 THP方案组治疗NHL26例，21d一个周期；MIT方案组治疗NHL25例，21d一个周期。结果 初发患者以THP为主方案治疗后有效率为81．81％，复发或难治患者的有效率为53．33％；MIT方案组治疗初发患者的有效率为75．00％，复发或难治患者的有效率为33．33％。THP及MIT治疗非霍奇金淋巴瘤的疗效无差异（P〉0．05）。结论 THP是治疗非霍奇金淋巴瘤的高效低毒的化疗药物。