A randomised,cross-over study comparing injection site pain with subcutaneous epoetin beta and subcutaneous darbepoetin alfa in patients with chronic kidney disease*

ABSTRACT

Objective: To compare injection site pain of subcutaneous (sc) epoetin beta and darbepoetin alfa in adult patients with chronic kidney disease.

Research design and methods: This was a multi-centre, randomised, two-arm, single-blind, cross-over study. Patients were randomised to receive weekly sc darbepoetin alfa 30?μg or weekly sc epoetin beta 6000?IU for 2 weeks and were then crossed over to the alternative treatment for 2 weeks. Injection site pain was assessed using a 10?cm ungraduated visual analogue scale (0?=?no pain, 10?=?worst pain) and a six-point verbal rating scale. Patient preference for treatment was also assessed.

Trial registration: http://clinicaltrials.gov/(NCT00377481).

Results: All randomised patients (N?=?48) completed the study. The sample comprised 29 chronic kidney disease patients (Stage 3 or Stage 4), 11 peritoneal dialysis patients and 8 renal transplant patients. Patients perceived significantly less pain with epoetin beta than darbepoetin alfa, using the visual analogue scale (relative pain score?=?2.75, darbepoetin alfa:epoetin beta, 95% CI: 1.85, 4.07; p?<?0.0001) and the verbal rating scale (median: 0.5, 95% CI: 0.5, 1.0 vs. median: 1.5, 95% CI: 1.0, 2.0; p?<?0.0001). Epoetin beta was preferred by significantly more patients (65%) than darbepoetin alfa (10%) (p?<?0.001); 25% of patients reported no preference.

Conclusions: Limitations included lack of an epoetin alfa comparator and limited blinding (patients were blinded to treatment, however, an unblinded nurse administered treatment). We show that sc injection of epoetin beta is significantly less painful than darbepoetin alfa and patient preference for epoetin beta confirms that the difference is clinically meaningful.     

Utilization of darbepoetin alfa and epoetin alfa for chemotherapy-induced anemia.

PURPOSE: The patterns of use and effectiveness of therapy with darbepoetin alfa and epoetin alfa for chemotherapy-induced anemia (CIA) in hospital outpatient and community settings were evaluated. METHODS: Data were collected from medical charts at 65 oncology clinics in hospital outpatient and community settings for consecutive patients who received the first dose of either darbepoetin alfa or epoetin alfa between August 1, 2002, and February 15, 2003, and were to have had 12 weeks of follow-up data. RESULTS: Data from the charts of 3123 patients were abstracted. Of these patients, 2785 were treated with only one erythropoietic agent (1444 with darbepoetin alfa and 1341 with epoetin alfa) and were included in the analysis. The most common initial dosage of darbepoetin alfa was 200 microg every two weeks (61% of darbepoetin alfa recipients), and the most common initial dosage of epoetin alfa was 40,000 units weekly (72%). With these regimens, the dosage was escalated for 22% of darbepoetin alfa recipients and 23% of epoetin alfa recipients at a median of six weeks after the initial dose. The mean change from baseline in hemoglobin concentration after 12 weeks of therapy was similar for both groups, as was the percent of patients with red-blood-cell transfusions during treatment. CONCLUSION: The most common initial dosage of darbepoetin alfa for CIA was 200 microg every two weeks, and the most common initial dosage of epoetin alfa was 40,000 units weekly. At these dosages, the two agents appear to have similar clinical effectiveness.     

Dose and cost comparison of erythropoietic agents in the inpatient hospital setting.

PURPOSE: The inpatient dosing patterns and treatment costs in cancer and predialysis chronic kidney disease (CKD) patients treated with erythropoietic agents from a hospital pharmacy perspective were studied. METHODS: An analysis of electronic inpatient records from the Premier Perspective comparative hospital database was conducted. Study participants were identified through hospitalizations recorded between July 2002 and March 2005 from over 500 hospitals nationwide. Adult patients with an admitting diagnosis of cancer or predialysis CKD and treated with epoetin alfa or darbepoetin alfa during hospitalization were included. Patients who had received renal dialysis or both agents during a hospitalization were excluded. Wholesale acquisition costs from September 2006 were used to calculate drug costs. RESULTS: A total of 25,645 hospitalized patients with cancer (22,873 received epoetin alfa; 2,772 received darbepoetin alfa) and 66,822 hospitalized patients with CKD (60,079 received epoetin alfa; 6,743 received darbepoetin alfa) were identified. The mean cumulative dose per hospitalization resulted in dose ratios of 245:1 and 242:1 (units epoetin alfa:micrograms darbepoetin alfa) for cancer and CKD patients, respectively. On the basis of the cumulative dose per hospitalization, drug costs for darbepoetin alfa-treated patients were approximately 50% higher than drug costs for epoetin alfa-treated patients for both oncology and CKD patients. CONCLUSION: Epoetin alfa was associated with less cost compared with darbepoetin alfa for treating inpatients with cancer or CKD. Further research including the patients' clinical outcomes is necessary to determine the true pharmacoeconomic differences between the two agents.     

Cost-minimization analysis of darbepoetin alfa versus epoetin alfa in the hospital setting.

PURPOSE: The cost of darbepoetin alfa versus that of epoetin alfa in a hospital setting was studied. METHODS: The study was an observational, retrospective review of the hospitalwide use of darbepoetin and epoetin during hospital admissions beginning in the period from January 2003 through April 2003. After the identification from daily charge reports of patients who used at least one of the study drugs during an admission, charts were requested for review. Drug product costs were determined from hospital purchasing information. Material and labor costs were combined to estimate drug administration costs. Total costs were calculated as the sum of drug product costs and administration costs. RESULTS: A total of 429 epoetin records and 80 darbepoetin records were included. The two cohorts were similar with respect to demographic characteristics. With respect to costs, the only significant difference between cohorts was in daily administration costs, which were lower for patients receiving darbepoetin. Sensitivity analysis found lower costs for darbepoetin only after the dose-conversion ratio (DCR) was increased to above 256.74 units:1 microg. The overall DCR based on the median daily dose of each drug was 244.90 units:1 microg. CONCLUSION: A cost-minimization study in a hospital showed no cost difference between treatment with epoetin and darbepoetin.     

Darbepoetin alfa.

Darbepoetin alfa is a novel erythropoiesis-stimulating protein developed for the treatment of anaemia associated with chronic kidney disease. In single-dose studies in patients undergoing dialysis, the mean terminal half-life for intravenous darbepoetin alfa was approximately 3-fold longer than for intravenous recombinant human erythropoitin (r-HuEPO, epoetin alfa; 25.3 vs 8.5 hours). The mean terminal half-life after subcutaneous administration of darbepoetin alfa was 48.8 hours. In randomised nonblind trials in patients undergoing dialysis, darbepoetin alfa (0.45 pg/kg) given once weekly for the correction of anaemia increased haemoglobin (Hb) levels to a similar extent as darbepoetin alfa three times weekly or r-HuEPO two or three times weekly. A double-blind, randomised clinical trial reported that switching patients from a three-times weekly regimen of r-HuEPO to once weekly darbepoetin alfa with additional placebo twice weekly (all intravenously) maintained Hb levels between 9.0 and 13.0 g/dl to a similar extent as continued treatment with r-HuEPO three times weekly. In a randomised nonblind study, r-HuEPO-naive patients with chronic renal insufficiency received either subcutaneous darbepoetin alfa once weekly or r-HuEPO twice weekly. 93% of patients receiving darbepoetin alfa and 92% of patients receiving r-HuEPO achieved a Hb increase of > or = 1.0 g/dl from baseline and the mean increase in Hb level over the initial 4 weeks was similar for both treatments. The number and frequency of adverse events, withdrawals and deaths reported in clinical trials did not differ between patients receiving darbepoetin alfa and patients receiving r-HuEPO. There have been no reports of immune responses to darbepoetin alfa in 1534 patients receiving treatment for up to 2 years.     

The relative dosing of epoetin alfa and darbepoetin alfa in chronic kidney disease

ABSTRACT

Objective: The purpose of this study was to review and analyze current research to evaluate the dose ratio of epoetin alfa and darbepoetin alfa for the treatment of anemia in chronic kidney disease (CKD) and to identify determinants of the variation in epoetin alfa: darbepoetin alfa dose ratios across studies.

Methods: A systematic review of the literature for comparative switch and non-switch studies of epoetin alfa and darbepoetin alfa treatments in CKD for the period 2000–2005 was performed. Two reviewers independently assessed the quality of the information. Data on the study design and outcomes were collected for each selected study. The dose ratio from epoetin alfa to darbepoetin alfa was calculated for each study, and the results were reported stratified by study characteristics. To control for differences in study design and characteristics that could explain the variability in the relative dosages of the two agents across studies, multivariate regression analysis was conducted. Based on these results, a dose conversion ratio for Canada was estimated.

Results: A total of 21 studies involving 16?378 patients exposed to epoetin alfa or darbepoetin alfa in CKD were identified. Univariate analysis of the dose ratios indicated a mean dose ratio of 217:1 (IU of epoetin alfa:µg of darbepoetin alfa). Results from the multivariate analysis demonstrated that the study design (i.e., switch study versus straight comparison studies) and geographical coverage (i.e., United States) affected the results. Based on the multivariate analysis, the dose conversion ratio between epoetin alfa and darbepoetin alfa for Canada was 169:1.

Conclusions: Despite limitations associated with switching studies and the limited total number of studies available, this systematic review based on aggregated results provides further evidence to the clinical community that the dose conversion ratio for epoetin alfa:darbepoetin alfa in CKD patients in Canada is approximately 169:1. At that ratio, treatment with epoetin alfa is 11–18% cheaper than treatment with darbepoetin alfa in Canada.     

Darbepoetin alfa: new indication/new dosage. No proven advantage in chemotherapy-induced anaemia

(1) Current treatments for anaemia in patients receiving cancer chemotherapy include blood transfusion and epoetin alfa and beta. These epoetins correct anaemia in 40% to 65% of patients and reduce the number of patients who require transfusions during the second and third months of treatment by 12-35% in absolute terms. (2) Darbepoetin alfa is slightly more glycosylated than epoetin alfa and beta. It is no more effective than these two drugs in chronic renal failure. Darbepoetin alfa is now approved for the treatment of anaemia in patients who are receiving chemotherapy for non myeloid malignancies. (3) Two placebo-controlled dose-finding studies and two placebo-controlled trials involving nearly 1000 patients in total have shown that darbepoetin alfa decreases the number of transfused patients by 17-25% in absolute terms, and that it probably reduces fatigue. However, one-quarter of patients receiving darbepoetin were nonetheless transfused. (4) In the absence of reliable comparisons, there is no firm evidence that darbepoetin alfa is more effective than other epoetins. (5) According to relatively imprecise company reports, darbepoetin alfa increased the risk of thromboembolic events during clinical trials (6% versus 3%), including pulmonary embolism (1.3% versus 0%); the company also states that darbepoetin alfa does not increase the risk of arterial hypertension, a classical effect of epoetin that is mentioned in the summary of product characteristics (SPC). Placebo-controlled trials and dose-finding studies show no impact on the outcome of cancer, but follow-up is limited and a negative effect cannot be ruled out. The company states that no cases of erythroblastopenia have occurred among more than 70 000 treated patients. (6) According to the SPC, darbepoetin alfa can be given once a week. However, the optimal epoetin dosing schedule is unknown. Epoetin therapy takes several weeks to correct anaemia, whereas transfusion is immediately effective. (7) In practice, darbepoetin alfa seems a little easier to administer than epoetin alfa or beta, but the advantages and disadvantages of these drugs as compared with blood transfusion are not entirely clear.     

Cost-minimization analysis of once-weekly versus thrice-weekly epoetin alfa for chemotherapy-related anemia

BACKGROUND: For individuals with chemotherapy-related anemia, the clinical effectiveness of epoetin alfa (EPO) dosed once weekly ([QW], 40,000 units per dose) has been demonstrated to be indistinguishable from that observed with thrice-weekly dosing ([TIW], 10,000 units per dose). Whether the advantage of less-frequent administration justifies the higher EPO dosage used in the weekly regimen in terms of overall cost of care is unknown. OBJECTIVE: To conduct a cost-minimization analysis comparing QW and TIW EPO dosing from a societal perspective. METHODS: Direct and indirect medical cost data were calculated for a 16-week period for 2 large, prospective, multicenter, community-based studies. Costs measured included EPO, transfusions, laboratory tests, office visits, and opportunity cost of patient time. RESULTS: The average total costs in 2002 (first half) dollars were nearly equivalent across the 2 groups (QW: 9,204 dollars; 95% confidence interval [CI], 9,057 dollars-9,350 dollars. TIW: 9,265 dollars; 95% CI, 9,083 dollars-9,447 dollars. P=0.60). QW incurred mean drug acquisition costs that were 23% higher (QW: 6,725 dollars; 95% CI, 6,611 dollars-6,838 dollars. TIW: 5,474 dollars; 95% CI, 5,350 dollars-5,598 dollars. P<0.001). However, QW patients can avoid the resource use and time cost associated with 2 additional office visits incurred each week (QW: 592 dollars [583 dollars-600 dollars]; TIW: 1,709 dollars [1,678 dollars-1,740 dollars]; P<0.001). Transfusion and laboratory test costs were slightly higher in the TIW group (QW: 1,888 dollars [1,837 dollars-1,940 dollars]; TIW: 2,082 dollars [2,020 dollars-2,144 dollars]; P<0.001). CONCLUSION: Total anemia treatment costs over a 16-week period with EPO QW were similar to those of TIW dosing. In the absence of cost differences between regimens, the noneconomic advantages of less-frequent dosing intervals should make weekly dosing increasingly attractive to patients, clinicians, and payers.     

Evaluation of the US Oncology Network's recommended guidelines for therapeutic substitution with darbepoetin alfa 200 microg every 2 weeks in both naïve patients and patients switched from epoetin alfa

STUDY OBJECTIVE: To evaluate the efficacy of darbepoetin alfa 200 microg subcutaneously every 2 weeks after therapeutic substitution for epoetin alfa. DESIGN: Retrospective multicenter chart review. SETTING: Three US Oncology-affiliated outpatient sites. PATIENTS: Three hundred thirty anemic patients with nonmyeloid malignancies, of whom 174 had been treated previously with epoetin alfa (switched group) and 156 had not been treated recently with epoetin alfa (naive group). INTERVENTIONS: Therapeutic substitution with darbepoetin alfa was started according to the US Oncology Pharmacy and Therapeutics Committee's recommended dosing guidelines: anemic patients with cancer received a starting dosage of darbepoetin alfa 200 microg every 2 weeks regardless of whether or not they had previously received epoetin alfa. Hematologic and darbepoetin alfa usage data were abstracted from consecutive medical records dated from May 2002-March 2003. MEASUREMENTS AND MAIN RESULTS: Median exposure to darbepoetin alfa was 10 weeks (25th quartile 6 wks, 75th quartile 17 wks) and 10 weeks (25th quartile 5 wks, 75th quartile 18 wks) for the naive and switched groups, respectively. The week before the switch to darbepoetin alfa, the 174 patients receiving epoetin alfa were administered the following weekly doses: less than 40,000 U (9%), 40,000 U (50%), or 45,000-90,000 U (41%). Mean hemoglobin level increased from baseline (wk 0) in both the naive and switched groups. The proportion of patients receiving a red blood cell transfusion in the darbepoetin alfa treatment phase was low (15% in each group). No variation in transfusion rates was observed across weight categories in patients who received a fixed dosage of darbepoetin alfa. Darbepoetin alfa was well tolerated. A detailed usage algorithm was validated by these results and is being used in these three US Oncology-affiliated practices. CONCLUSION: A darbepoetin alfa starting dosage of 200 microg subcutaneously every 2 weeks administered according to US Oncology-recommended dosing guidelines is effective in treating chemotherapy-induced anemia in both epoetin alfa-naive patients and those switched from epoetin alfa.     

Use and cost of erythropoiesis-stimulating agents in patients with cancer

ABSTRACT

Objective: To compare the baseline characteristics, episodes of care, and cost of erythropoiesis-stimulating agents among cancer patients in a US managed-care population.

Research design and methods: Retrospective analysis of administrative claims data. Episodes of care for patients with cancer receiving erythropoiesis-stimulating agents between January 1, 2004 and January 17, 2006 included all claims for erythropoiesis-stimulating agents with ≤42 days’ gap between claims, plus the duration of therapeutic benefit based on median days between consecutive doses.

Main outcome measures: Main outcome measures were average weekly dose of erythropoiesis-stimulating agents and costs of therapy.

Results: A total of 15?007 eligible episodes of care (darbepoetin alfa, 7769 episodes [5587 patients]; epoetin alfa 7238 episodes [5157 patients]) were identified. Fewer claims were observed per episode of care for darbepoetin alfa than for epoetin alfa (mean [SD] 3.7 [4.1] vs. 5.3 [6.4]). The median time between consecutive claims was 15 days (darbepoetin alfa) and 8 days (epoetin alfa). The mean (SD) weekly doses were 105 (56)?μg (darbepoetin alfa) and 34?242 (28173) U (epoetin alfa), a dose-comparison ratio of 326?:?1.

Dose-comparison ratios were sensitive to assumptions about duration of clinical benefit.

The mean (95% CI) weekly costs were significantly lower for darbepoetin alfa ($560 [553–567]) than for epoetin alfa ($645 [630–659], p < 0.0001) when duration of clinical benefit was considered.

Conclusions: Significant differences characterize patterns of use of erythropoiesis-stimulating agents. Duration of therapeutic benefit is an important variable in comparing darbepoetin alfa with epoetin alfa; incorporation of this variable in analyses of costs of therapy may have notable effects on calculated treatment costs. Limitations of the study include the potential for database errors or omissions, lack of detailed disease data, and lack of adjustment for differences in the ages and comorbidities of patients.     

Análisis probabilístico de minimización de costes de darbepoetin alfa frente a epoetina alfa en el tratamiento de la anemia secundaria a insuficiencia renal crónica. Valoración en la práctica clínica española

IntroductionThe direct transfer of the results of pharmaco-economic studies between countries may not be suitable if the proper adaptations are not made to take into account differences in treatment patterns, resource use and costs from country to country.ObjectiveTo estimate the cost in Spain of treating anaemia secondary to chronic renal failure with darbepoetin alpha or epoetin alpha from a review and analysis of available current information. In addition, the role of the route of administration as a main driver of the cost will be analysed.MethodPopulation: patients with chronic kidney failure induced anaemia. Data: Medline and Embase search of studies directly comparing erythropoiesis stimulating agents. Analysis: Cost minimization analysis from the perspective of a hospital pharmacy department. The main outcome chosen was the difference between the average cost per patient undergoing a 30-day treatment with epoetin alpha versus darbepoetin alpha.Resultsa) haemodialysis: changing from epoetin alpha to darbepoetin alpha is associated with a cost reduction of 8.67 %; CI 95 %, ?1.34 to 17.92 (€ 17.48; CI 95 %, ?2.70 to 36.13); probabilistic analysis showed that the use of darbepoetin alpha could be associated with a cost-saving probability of 94.9 %. The IV administration yielded a decrease in costs of about 16.00 %; CI 95 %, ?2.38 to 36.77 (€ 41.78, CI 95 %: ?6.21 to 96.04). b) Pre-dialysis: darbepoetin alpha is associated with a cost reduction of about 11-32 %.ConclusionsThe use of darbepoetin alpha for the treatment of chronic renal failure induced anaemia (haemodialysis and pre-dialysis) shows higher cost efficiency than epoetin alpha in Spain; these differences increase with IV administration.     

Darbepoetin alfa: new preparation. Just a me-too: no advantage in anaemia of chronic renal failure

(1) Darbepoetin alfa, an epoetin, is slightly more glycosylated than epoetin alfa and beta. (2) The clinical file on anaemic patients with chronic kidney failure shows no advantage of darbepoetin alfa over other epoetins in terms of efficacy or side effects (subcutaneous injections of darbepoetin alfa are more often painful). (3) The dosing schedules of epoetins have not been compared adequately. Dosing schedules should be adapted for each patient.     

Dosing patterns, hematologic outcomes, and costs of erythropoietic agents in predialysis chronic kidney disease patients with anemia

OBJECTIVE: Few observational studies have evaluated the use of epoetin alfa (EPO) and darbepoetin alfa (DARB) in chronic kidney disease (CKD) patients with anemia. The objective of this study was to investigate dosing patterns, hematologic outcomes, and intervention costs with EPO and DARB in anemic CKD patients treated in an ambulatory care setting. METHODS: This was a multicenter, retrospective, chart review of predialysis CKD patients with anemia treated with EPO or DARB. Charts were sequentially selected from 435 EPO and 432 DARB patients naive to erythropoietic therapy and treated for > or = 24 weeks. Hemoglobin (Hb) levels, dates, and EPO/DARB doses were recorded. Drug costs using 2005 wholesale acquisition costs (WAC) and Federal Supply Schedule (FSS) pricing were based on the mean cumulative drug dose over the 24-week study period. RESULTS: A total of 393 EPO and 396 DARB charts met all criteria with predominantly male subjects (EPO: 94%; DARB: 96%). Mean baseline GFR and Hb levels were similar. Once-weekly and extended dosing (> or = Q2W) was common in both groups. At Weeks 4, 8, and 12 following initiation of therapy, a greater proportion of EPO than DARB patients reached target Hb levels (> or = 11 g/dL) (p < 0.0001); at Week 24, all patients reached target Hb levels. Mean 24-week cumulative doses were EPO 279 336 +/- 68 302 units and DARB 1084 +/- 246 microg. Drug cost was higher for DARB independent of pricing utilized (WAC: EPO = 3400 US dollars, DARB = 4726 US dollars; FSS: EPO = 1528 US dollars, DARB = 2379 US dollars). CONCLUSIONS: Extended dosing (Q2W) was common in EPO- and DARB-treated patients with CKD-related anemia, with EPO-treated patients experiencing a significantly greater hematologic response (at Weeks 4, 8, and 12). In addition, drug cost was 39-56% higher in the DARB group. The male predominance may limit generalizability, warranting further research in other populations.     

Current and future options for the treatment of chemotherapy-induced anaemia

Chemotherapy-induced anaemia (CIA) is a significant source of morbidity in patients receiving treatment for cancer. There are three products currently available for the treatment of CIA: epoetin alfa, epoetin beta and darbepoetin alfa. Several organisations have published recommendations for the use of these agents. Several randomised, controlled trials have been conducted comparing the most popular dosing regimens of epoetin alfa and darbepoetin alfa, with conflicting results. Information regarding survival and adverse event data related to these agents continues to create debate. This review considers four new agents that are under development for the treatment of CIA.     

Current and future options for the treatment of chemotherapy-induced anaemia

Chemotherapy-induced anaemia (CIA) is a significant source of morbidity in patients receiving treatment for cancer. There are three products currently available for the treatment of CIA: epoetin alfa, epoetin beta and darbepoetin alfa. Several organisations have published recommendations for the use of these agents. Several randomised, controlled trials have been conducted comparing the most popular dosing regimens of epoetin alfa and darbepoetin alfa, with conflicting results. Information regarding survival and adverse event data related to these agents continues to create debate. This review considers four new agents that are under development for the treatment of CIA.     

Cost-effectiveness of epoetin alfa therapy for anemia of end-stage renal disease.

The cost-effectiveness of epoetin alfa therapy for anemia in 20 patients with end-stage renal disease was retrospectively studied. Ten patients on continuous ambulatory peritoneal dialysis (CAPD) were given subcutaneous epoetin alfa as part of a multicenter, protocol-controlled study of the efficacy of epoetin alfa. Ten patients on in-center hemodialysis were given intravenous epoetin alfa as part of their routine clinical care. Change in hematocrit was used as the measure of effectiveness of epoetin alfa. Medication, laboratory, and transfusion costs were monitored for the six months preceding the initiation of epoetin alfa and the first six months of treatment. The cost of therapy increased for all patients by an average of $2722 +/- 1118; transfusion costs decreased, whereas medication and laboratory costs increased. Laboratory costs were significantly greater in CAPD patients than in hemodialysis patients during epoetin alfa therapy; no significant differences in medication costs or transfusion costs were noted between the groups. The mean increase in hematocrit for all patients was 7.4 volume percent. Following the initial change in hematocrit, further therapeutic response did not appear to be determined by increasing expenditures. Epoetin alfa was shown to be effective in treating anemia in patients with end-stage renal disease, but it was associated with higher costs of therapy.     

Epoetins and [symbol: see text] darbepoetin alfa in malignant disease

Anaemia is common in people with cancer, and may reduce their quality of life and life expectancy. Blood transfusion can increase haemoglobin levels but is usually reserved for those with moderate anaemia (haemoglobin level below 10 g/dL). A potential alternative is treatment with one of the human recombinant forms of erythropoietin, epoetin alfa (Eprex--Janssen-Cilag) or epoetin beta (NeoRecormon--Roche), or their hyperglycosylated derivative [symbol: see text] darbepoetin alfa (Aranesp--Amgen). These products have improved the management of patients with chronic renal failure who are anaemic. Here we assess the place of the epoetins and darbepoetin alfa in managing anaemia in patients with cancer.     

Cost implications of post-surgical morbidity following blood transfusion in cancer patients undergoing elective colorectal resection: an evaluation in the US hospital setting

OBJECTIVE: To estimate the cost implications of blood transfusions and related surgical site infections (SSIs) in cancer patients undergoing elective colorectal resection in the hospital setting in the United States (US). STUDY DESIGN: A modelling study was performed from the perspective of the hospital sector, based on published clinical outcomes from a study in Taiwan involving 2809 cancer patients who underwent elective colorectal resection using laparotomy and American treatment patterns. METHODS: Data on resource use were retrieved from published literature and from two American hospital centres specialising in colorectal cancer management. Decision analytical modelling was used to estimate the treatment costs and consequences of managing patients undergoing elective colorectal resection with and without blood transfusions. RESULTS: The expected treatment costs of managing patients who required and did not require a blood transfusion were estimated to be US dollars 19,869 (95% CI: 15 797; 23 150) and US dollars 14,586 (95% CI: 14 263; 14 886) per patient respectively. Expected treatment costs for those patients transfused with 1-3 units and > 3 units of blood were estimated to be US dollars 17,449 and US dollars 22,588 per patient respectively. CONCLUSION: This is one of the first studies to specifically address the cost implications of postsurgical morbidity following colorectal resection in cancer patients. The cost of managing cancer patients undergoing elective colorectal resection who require a blood transfusion is expected to be 36% more than that of non-transfused patients, largely resulting from the development of SSIs.     

Extended-dosage-interval regimens of erythropoietic agents in chemotherapy-induced anemia.

PURPOSE: The safety and efficacy of extended-dosage-interval regimens of erythropoiesis-stimulating agents (ESAs) for managing chemotherapy-induced anemia (CIA) are reviewed. SUMMARY: Anemia is a frequent complication of chemotherapy. The ESAs epoetin alfa and darbepoetin alfa have been shown to safely and effectively manage CIA; comparable outcomes have been demonstrated between epoetin alfa 40,000 units once weekly and darbepoetin alfa 200 microg every two weeks. These commonly prescribed regimens necessitate extra clinic visits by cancer patients receiving cyclic chemotherapy. ESA administration can now often be synchronized with a three-week chemotherapy cycle because of the recent approval of darbepoetin alfa 500 microg every three weeks for CIA. However, in the Phase III trial providing the basis for this new dosage recommendation, more than 70% of patients required a 40% reduction in the dosage, resulting in an average dose of 375 microg every three weeks. The extended-dosage-interval regimens have not been associated with an increase in cardiovascular or thrombotic adverse events. Extended-dosage-interval regimens of epoetin alfa are under investigation and may provide additional alternatives. Synchronizing ESA therapy with scheduled chemotherapy visits would help minimize disruptions for patients and caregivers and improve the use of health care resources. CONCLUSION: Administration of darbepoetin alfa every three weeks offers the convenience of synchronization of treatment with 21-day-cycle chemotherapy in many patients with CIA. Extended-dosage-interval regimens for epoetin alfa are being investigated and show promise.