Linear Analog Scale Assessment Research Articles

Cognitive Effects of Once Weekly (QW) Epoetin Alfa in Anemic Patients (pts) with Hematologic Malignancies Receiving Chemotherapy (CT): Interim Results of the EPOLYM Trial.

CT-associated cognitive dysfunction, which frequently manifests as subtle changes in memory, concentration, and ability to remain focused or organized, can adversely affect cancer pts' QOL. EPOLYM, a prospective, international, multicenter, open-label, phase IIIb trial has been conducted to investigate the efficacy, safety, and clinical outcomes, including effect on cognitive function, of epoetin alfa 40,000 IU sc QW in anemic (Hb <12 g/dL) pts with hematologic malignancies. Pts enrolled had either non-Hodgkin's lymphoma, multiple myeloma, Hodgkin's disease, or chronic lymphocytic leukemia, for which they were receiving or were expected to receive CT (planned N = 1,000). Dosage increases or decreases were to be made based on clinical response (target Hb, 11.5–13.0 g/dL). Cognitive function was evaluated from baseline to Week 24 (or last evaluation) using the Cognitive Drug Research Computerised Cognitive Assessment System, patient-completed, computer-scored tasks of attention (Simple Reaction Time, Choice Reaction Time, Digit Vigilance), working memory (Numeric Working Memory), and secondary memory (Immediate and Delayed Word Recognition, Picture Recognition). To further characterize the data, task scores were variously summed to provide 4 factor scores (and aspects of cognitive function measured): Power of Attention (concentration intensity), Continuity of Attention (ability to sustain concentration), Quality of Memory (amount of information that can be stored and successfully retrieved in working and long-term memory), and Speed of Memory (speed in ability to recognize information previously presented or held in working memory). Changes from baseline in Hb levels and transfusion requirements were determined and QOL was assessed using the Functional Assessment of Cancer Therapy-Anemia Subscale and the Linear Analog Scale Assessment. Because of the apparent relationship between affect and cognition, anxiety and depression were evaluated at the time of cognitive assessment using the Hospital Anxiety and Depression Scale (HADS). Transfusion, QOL, and HADS results are not considered here. The cognitive data for 568 pts who had completed up to 24 weeks of therapy were examined in an interim analysis. Results showed that Power of Attention was slightly impaired and Continuity of Attention was slightly improved over the course of the study; however, these effects were small and unlikely to have everyday behavioral significance. Greater changes were observed in regard to memory. Mean Speed of Memory was decreased 358.9 msec by Week 24, representing an 8% improvement from baseline. Also, improvement was noted in Quality of Memory, with the score for this factor increased by 0.0899 at Week 24 from a baseline value of 2.895. The improvement in cognitive function was associated with an increase in Hb from 10.5 g/dL at baseline to about 12 g/dL beginning at Weeks 8 to 12 and sustained for up to 24 weeks. Results of this interim analysis suggest improvement in several aspects of cognitive function associated with increased Hb levels in anemic CT pts with hematologic malignancies. These results will have to be confirmed by findings based on the full study cohort.

Epoetin Alfa 40,000 U QW Increases Hb and Is Safe in Anemic Patients with Cancer Not Receiving Chemotherapy or Radiation Therapy.

Patients (pts) with cancer often become anemic as a result of the disease and its treatment. Epoetin alfa (EPO) administered 150 U/kg SC 3 times a week in pts with cancer-related anemia not receiving chemotherapy (CT) or radiation therapy (RT) significantly reduces transfusion requirements, increases hemoglobin (Hb), and improves quality of life (QOL). EPO 40,000 U SC QW is effective in pts with cancer-related anemia receiving CT +/− RT and may be a treatment option for pts not receiving CT or RT. This open-label, multicenter, pilot study investigated clinical outcomes and safety of EPO 40,000 U SC QW in anemic (Hb <11 g/dL) pts with cancer not receiving CT or RT. Treatment duration was up to 12 wks with a 4-wk posttreatment observation period. If Hb increased <1 g/dL after 4 wks, dose was increased to 60,000 U SC QW. EPO dose was reduced for Hb >15 g/dL; dose reduction was considered for Hb increase >1.3 g/dL over 2 wks in the original protocol. Primary endpoint was proportion of pts achieving a ≥1-g/dL or ≥2-g/dL increase in Hb from baseline (BL; independent of transfusion within the previous 28 days) at any time during the study. Secondary endpoints included transfusion requirements and QOL (measured with the Linear Analog Scale Assessment; LASA). The study was temporarily suspended due to concerns of a potential increased risk of thrombotic events if Hb >13 g/dL, and restarted with an upper Hb limit of 13 g/dL and rate of rise of Hb of 1 g/dL over any consecutive 2-wk period, independent of transfusion. Due to the interruption in therapy, 3 efficacy populations were evaluated: pts who had a post BL Hb value or transfusion (modified intent-to-treat [MITT], n=91); pts who completed the study prior to suspension (presuspension, n=37); and pts who entered the study, had treatment suspended, and completed after the study was restarted (suspension, n=33). Ninety-five pts were evaluable for safety: mean age, 69 years; 45% women; 85% ECOG 0-1; mean BL Hb 10.4 ± 0.73 g/dL. For the 3 populations analyzed, 73/91 (80%), 33/37 (89%), and 29/33 (88%) pts had an Hb increase ≥2 g/dL for the MITT, presuspension, and suspension populations, respectively. 13/91 (14%), 2/37 (5%), and 3/33 (9%) pts had at best an Hb increase ≥1 g/dL for the MITT, presuspension, and suspension populations, respectively. For the MITT population, mean change in Hb from BL after 12 wks was 2.9 ± 1.54 g/dL. Mean Hb decreased 1.4 ± 1.10 g/dL during the posttreatment observation period.One pt was transfused on study. Both wk 9 and wk 17 LASA scores increased significantly from BL in all categories (Energy Level, Daily Activities, and Overall QOL; P<0.001). EPO dose was increased in 15 (16%) pts and decreased or held in 61 (64%) pts during the study. Mean time to first dose reduction or hold was 38 days. Most commonly reported AEs were fatigue (19%) and nausea (13%). Twenty-four (25%) pts had ≥1 serious AE. Four (4%) pts discontinued due to an AE. One pt died on study due to disease progression. Two (2%) pts had a clinically relevant thrombovascular event (deep vein thrombosis [DVT]); 1 pt was in the presuspension population and had Hb 13.5 g/dL prior to the DVT, the other pt was in the suspension population and had Hb 11.9 g/dL prior to the DVT. Irrespective of the population analyzed, 80%–89% of pts had at least a 2-g/dL increase in Hb at some point during the study, suggesting that EPO 40,000 U SC QW is effective and safe in pts with cancer-related anemia not receiving CT or RT.

Greater Area under the Hemoglobin Change Curve Is Associated with Improved Outcomes in Elderly Patients Receiving Epoetin Alfa for Chemotherapy-Related Anemia.

Background: Several measures have been used to assess the efficacy of erythropoietic agents in patients with chemotherapy-related anemia (CRA). Previous research has demonstrated the area under the 16-week hemoglobin (Hb) change curve (Hb AUC16) as a sensitive and comprehensive efficacy measure compared to traditional single time point or threshold-based measures. Higher Hb AUC16 values during epoetin alfa (EPO) therapy in patients with CRA are associated with reduced transfusion requirements, improved quality of life, increased hematologic response rates, and decreased EPO utilization. This subgroup analysis of elderly patients with CRA evaluates the clinical significance of higher Hb AUC16 values in this unique population.Methods: Data from three, large, multicenter EPO clinical trials were evaluated. In EPO 1, patients received 10,000 Units TIW with potential escalation to 20,000 Units TIW. In EPO 2 and EPO 3 patients received 40,000 Units QW with potential escalation to 60,000 Units QW. Eligible patients for this analysis were >/=65 years, had a baseline Hb </=11g/dL, had a non myeloid malignancy and received chemotherapy with or without radiotherapy (EPO 1: N=935: EPO 2: N=1,270; EPO 3: N=269). Hb AUC16 was calculated using sequential trapezoidal methodology based on the Hb change and was stratified into quartiles to assess trends in outcome measures. Trend tests were performed to determine if the following outcomes had significant linear trends across the Hb AUC16 quartiles: proportion of patients transfused, hematopoietic response (Hb rise >/= 2 g/dL over baseline or Hb >/= 12 g/dL during study), EPO utilization, and quality of life [assessed by the Linear Analogue Scale Assessment (LASA, all studies) and the anemia subscale of the FACT-An (EPO 1 and EPO 2)].Results: Greater Hb AUC16 values had a strong linear association with a decreasing proportion of patients transfused (p<.0001), increasing hematopoietic response rate (p<.0001), decreasing average weekly EPO dose (p<.0001), increasing LASA scores in all studies (p<.001) and FACT-An scores in EPO 1 and EPO 2 (p<.001).Conclusions: In the elderly patient subset, greater Hb AUC16 values were associated with significant improvement in clinical outcomes including the percentage of patients transfused, hematopoietic response rates, QOL score improvements, and EPO utilization. Hb AUC16 is an objective and meaningful metric that summarizes hematologic response over the course of treatment and is associated with clinical benefits in elderly patients receiving erythropoietic therapy.

Increasing Hemoglobin Levels with Epoetin Alfa in Anemic Hematologic Cancer Patients Receiving Chemotherapy Correlates Significantly with Improved Quality of Life.

The majority of patients (pts) with hematologic malignancies (HM) are anemic and often have poor performance scores (Ludwig H et al. Blood. 2002; 100:234a). The correlation between increases in hemoglobin (Hb) with epoetin alfa and improvements in quality of life (QOL) was evaluated in this open-label, multicenter study that enrolled 736 adult pts with various solid tumors and HM (n = 122) who were receiving cytotoxic chemotherapy and had Hb levels <12 g/dL. Epoetin alfa was administered 150 IU/kg or 10,000 IU 3 times weekly (TIW) for a maximum 28 weeks (wks); dose was increased to 300 IU/kg or 20,000 IU TIW if Hb was not increased >1 g/dL above baseline within 4 wks. Results for pts with HM are compared to results from a similar 16-wk trial that included pts with HM (n = 488) and used the 40,000 IU once-weekly (QW) dose, increased to 60,000 IU QW if Hb did not increase ≥1 g/dL within 4 wks (Gabrilove J et al. Int J Hematol. 2000; 72:55). In the TIW study, the primary efficacy endpoint was change in QOL as measured by the Functional Assessment of Cancer Therapy-General (FACT-G), including subscales for anemia (FACT-An) and fatigue; the FACT was administered at study entry, at 8–9 wks, and at 12 wks. QOL was additionally measured by the Cancer Linear Analog Scale (CLAS; also known as the Linear Analog Scale Assessment [LASA]) administered at every study visit. Dose increases were similar in both studies (33.6% of pts in the TIW study; 36.7% of pts in the QW study). In the TIW study, mean baseline Hb was 9.6 g/dL; mean Hb increased at 4–6 wks (1.35 g/dL), 8–9 wks (2.09 g/dL) and 12 wks (2.46 g/dL) to a mean Hb of 12.0 g/dL. Almost half the HM patients in the TIW study (48.1%) had a complete response (Hb increase ≥2 g/dL without blood transfusion). Hematologic results are similar to those reported in the QW study where mean Hb increased 1.96 g/dL by end of study (P = .0001). QOL improvements were also similar between studies. Mean FACT-An scores for the total population in the TIW study increased 6.7 points after 12 wks, which is clinically significant (Patrick DL et al. Eur J Cancer. 2003; 39:335–345). The mean increase for overall FACT-G correlated significantly with increased Hb at 12 wks (P <.0001; r = .262). Mean CLAS scores for the total population increased steadily throughout the study. At 12 wks mean increases (based on the 100-mm scale) were clinically significant (Patrick et al): 10.9 mm for Energy, 11.2 mm for Daily Activity, and 10.3 mm for Overall QOL. Mean change for FACT-An for patients from the total population in the QW study (n = 2,230) was 6.0 points (P <.001), which is comparable to the mean changes in the TIW study and the HM population of the QW study (6.59 points, P <.0001). No unexpected adverse events were reported. Epoetin alfa TIW or QW was shown to steadily increase Hb, which significantly correlated with clinically significant improvements in QOL.

Once-Weekly Epoetin Alfa Improves Quality of Life and Increases Hemoglobin in Anemic HIV+Patients

This prospective, open-label, multicenter trial evaluated the effects of once-weekly (qw) epoetin alfa on quality of life (QOL) and hemoglobin (Hb) levels in anemic human immunodeficiency virus (HIV)-infected adult receiving antiretroviral therapy. A total of 650 patients with Hb < or = 11 g/dl received epoetin alfa 40,000 U qw subcutaneously, with dose escalation to 60,000 qw if Hb increase was <1 g/dl after 4 weeks. The linear Analog Scale Assessment (LASA) overall QOL score, LASA energy score, and LASA activity score each significantly improved from baseline to final measurement (p < 0.0001 for each parameter). Improvements in the Medical Outcomes Study (MOS)-HIV physical and mental health summary scores were also significant (p < 0.0001), and coincided with Hb increases. Mean Hb increased from baseline to final measurement by 2.5 g/dl (95% CI: 2.3, 2.6 g/dl; p < 0.0001). Objective hematological response rate, defined as a > or = 1 g/dl Hb increase from baseline to week 8, was 86%. Hemoglobin increased significantly in all subgroups of race, zidovudine use, CD4+ cell count, and viral load. Once-weekly epoetin alfa was well tolerated. Once-weekly epoetin alfa is effective in improving QOL and Hb measures.

Relationship Between Hemoglobin Levels and Quality of Life During Radiation Therapy Plus Concomitant or Sequential Chemotherapy in Patients With Cancer and Anemia Treated With Epoetin Alfa

This study in patients with cancer and anemia, who were receiving chemoradiation and were treated with epoetin alfa, examined the relationship between hemoglobin level and quality of life (QOL), change in hemoglobin and change in QOL, and incremental (1 g/dL) increase in hemoglobin and related incremental improvement in QOL. Data from a multicenter, open-label, prospective study of once-weekly epoetin alfa therapy in anemic cancer patients receiving chemoradiation were used to retrospectively evaluate the relationship between hemoglobin changes and QOL changes via correlation and longitudinal analyses. A sample selection correction method was used to ensure unbiased results. QOL (energy, activity, overall QOL) was measured using the Linear Analog Scale Assessment. An incremental analysis determined the greatest incremental increase in QOL associated with a 1 g/dL increase in hemoglobin level. Of the 777 patients enrolled, 464 met chemotherapy and radiotherapy eligibility criteria. Of these, 359 (77%) underwent two QOL assessments and were eligible for analysis. A nonlinear and statistically significant positive correlation was found between hemoglobin levels and Linear Analog Scale Assessment QOL scores (r = 0.32 [energy], 0.33 [activity], and 0.29 [overall QOL]; P < .0001). An incremental analysis used regression methods to characterize the changes in hemoglobin levels and QOL scores. Hemoglobin change was found to be a statistically significant determinant of QOL changes (P < .05). The greatest incremental QOL gain associated with a 1-g/dL change in hemoglobin occurred around hemoglobin 12 g/dL (range, 11-13 g/dL). A direct relationship exists between hemoglobin increases and corresponding QOL increases. Maximal incremental gain in QOL occurred when hemoglobin was approximately 12 g/dL (range, 11-13 g/dL).

Anemia and fatigue during adjuvant chemotherapy for breast cancer: Patterns and impact on quality of life

8060 Background: Research has failed to delineate a consistent pattern of fatigue and anemia & their impact on quality of life (QOL) during adjuvant breast cancer (BrCA) chemotherapy. Methods: Aims: To define the incidence and patterns of anemia and fatigue during and after adjuvant BrCA chemotherapy, & to determine relationships between anemia, fatigue, and QOL. We enrolled 110 patients with Stage I-III BrCA receiving either 4 cycles of Adriamycin & Cytoxan (AC) or AC followed by a taxane for 4 cycles (AC-T). Hemoglobin (Hb) values were obtained on day 1 of each cycle, as well as 6 weeks & 3 months after completion of chemotherapy. Piper Fatigue Scale total scores (PFS) and Linear Analog Scale Assessment (LASA) QOL scores were obtained on day 1 and 8 of cycles 1, 4, 5, and 8 as well as 6 weeks and 3 months following chemotherapy. Results: Mean Hb at baseline was 12.9 g/dL, decreased (p= 0.00) to 11.7 by Cycle 4 in all patients and Cycle 8 in individuals receiving AC-T. By 3 months post-chemotherapy, Hb recovered to baseline. Fatigue was generally mild (0 - 3) to moderate (4–6). Mean PFS scores increased from cycle 1 [(Cycle 1 day 1 = 2.63) and (Cycle 1 day 8 = 3.97) to cycle 4 [(day 1 = 3.87 and (day 8 = 5.10)] in all subjects, and from cycle 1 to cycle 8 ([Cycle 8 day 1 = 4.75], and [Cycle 8 day 8 = 5.15]) in AC-T. Fatigue was worse one week following chemotherapy. All results were significant at p<0.001. Finally, the impact of anemia on fatigue and QOL was explored by categorizing Hb at Cycle 4 into values < 11.5 and ≥ 11.5 g/dl. Although these groups did not significantly differ (p = 0.14) on PFS scores, 81% of patients with a Hb < 11.5 had moderate to severe fatigue, as compared to only 44% of those with Hb≥ 11.5 g/dl. Additionally, individuals with Hb < 11.5 had significantly lower QOL on the LASA (p = 0.008). Conclusions: Both anemia and fatigue increase over time across adjuvant BrCA chemotherapy, & fatigue worsens during the week following chemotherapy. In addition, preliminary evidence exists to validate Crawford's (2002) incremental analysis data demonstrating that the most significant increase in quality of life related to hemoglobin occurs between the values of 11 to 12 g/dl. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech, Inc.

Anemia and fatigue during adjuvant chemotherapy for breast cancer: Patterns and impact on quality of life

8060 Background: Research has failed to delineate a consistent pattern of fatigue and anemia & their impact on quality of life (QOL) during adjuvant breast cancer (BrCA) chemotherapy. Methods: Aims: To define the incidence and patterns of anemia and fatigue during and after adjuvant BrCA chemotherapy, & to determine relationships between anemia, fatigue, and QOL. We enrolled 110 patients with Stage I-III BrCA receiving either 4 cycles of Adriamycin & Cytoxan (AC) or AC followed by a taxane for 4 cycles (AC-T). Hemoglobin (Hb) values were obtained on day 1 of each cycle, as well as 6 weeks & 3 months after completion of chemotherapy. Piper Fatigue Scale total scores (PFS) and Linear Analog Scale Assessment (LASA) QOL scores were obtained on day 1 and 8 of cycles 1, 4, 5, and 8 as well as 6 weeks and 3 months following chemotherapy. Results: Mean Hb at baseline was 12.9 g/dL, decreased (p= 0.00) to 11.7 by Cycle 4 in all patients and Cycle 8 in individuals receiving AC-T. By 3 months post-chemotherapy, Hb recovered to baseline. Fatigue was generally mild (0 - 3) to moderate (4–6). Mean PFS scores increased from cycle 1 [(Cycle 1 day 1 = 2.63) and (Cycle 1 day 8 = 3.97) to cycle 4 [(day 1 = 3.87 and (day 8 = 5.10)] in all subjects, and from cycle 1 to cycle 8 ([Cycle 8 day 1 = 4.75], and [Cycle 8 day 8 = 5.15]) in AC-T. Fatigue was worse one week following chemotherapy. All results were significant at p<0.001. Finally, the impact of anemia on fatigue and QOL was explored by categorizing Hb at Cycle 4 into values < 11.5 and ≥ 11.5 g/dl. Although these groups did not significantly differ (p = 0.14) on PFS scores, 81% of patients with a Hb < 11.5 had moderate to severe fatigue, as compared to only 44% of those with Hb≥ 11.5 g/dl. Additionally, individuals with Hb < 11.5 had significantly lower QOL on the LASA (p = 0.008). Conclusions: Both anemia and fatigue increase over time across adjuvant BrCA chemotherapy, & fatigue worsens during the week following chemotherapy. In addition, preliminary evidence exists to validate Crawford's (2002) incremental analysis data demonstrating that the most significant increase in quality of life related to hemoglobin occurs between the values of 11 to 12 g/dl. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech, Inc.

Comparison of anemia outcomes associated with early response to epoetin alfa (EPO) withQW and TIW dosing

6141 Background: Anemia is a common side effect in patients receiving myelosuppressive chemotherapy. This study evaluates whether patients (pts) experiencing an early EPO response (at least 1g/dL hemoglobin (Hb) rise at 4 weeks independent of transfusion in the prior 28 days) had better clinical outcomes by end of study (EOS) compared with late/non-responders (<1g/dL Hb increase at 4 weeks). Methods: Data sets from three 16-week EPO multicenter clinical trials were used (EPO 1: N=2,964; EPO 2: N=681, EPO 3: N=2,289). In EPO 1 and 2, pts received 40,000 U QW with potential for escalation to 60,000 U; in EPO 3, pts received 10,000 U TIW with potential escalation to 20,000 U TIW. Study pts were adults who had a baseline Hb of less than or equal to 11g/dL, and received chemotherapy with or without radiotherapy for treatment of nonmyeloid malignancies. Outcomes included change in quality of life (QoL) measured by Linear Analog Scale Assessment and Functional Assessment of Cancer Therapy -Anemia and Fatigue (la...

Comparison of anemia outcomes associated with early response to epoetin alfa (EPO) withQW and TIW dosing

6141 Background: Anemia is a common side effect in patients receiving myelosuppressive chemotherapy. This study evaluates whether patients (pts) experiencing an early EPO response (at least 1g/dL hemoglobin (Hb) rise at 4 weeks independent of transfusion in the prior 28 days) had better clinical outcomes by end of study (EOS) compared with late/non-responders (<1g/dL Hb increase at 4 weeks). Methods: Data sets from three 16-week EPO multicenter clinical trials were used (EPO 1: N=2,964; EPO 2: N=681, EPO 3: N=2,289). In EPO 1 and 2, pts received 40,000 U QW with potential for escalation to 60,000 U; in EPO 3, pts received 10,000 U TIW with potential escalation to 20,000 U TIW. Study pts were adults who had a baseline Hb of less than or equal to 11g/dL, and received chemotherapy with or without radiotherapy for treatment of nonmyeloid malignancies. Outcomes included change in quality of life (QoL) measured by Linear Analog Scale Assessment and Functional Assessment of Cancer Therapy -Anemia and Fatigue (latter available for EPO 1 and EPO 3), transfusion use and Hb response (Hb rise of at least 2g/dL independent of transfusion ) between Week 5 and EOS. Results: Early response was observed in 47.1%, 48.9%, and 51.8% of pts from EPO 1, 2, and 3 respectively. Both intent-to-treat and on-treatment analyses yielded similar results, indicating early responders had significantly higher mean change scores than late/non-responders by EOS across all QoL instruments, after controlling for age, gender, tumor type, baseline ECOG score, baseline QoL score, change in Hb after Week 4, tumor response, and chemotherapy. Transfusion use was significantly lower for early responders than for late/non-responders (EPO 1: 5.1% vs. 20.3%, EPO 2: 7.6% vs. 20.1%, EPO 3 7.7% v. 26.8%, all p<0.0001). Hb response was significantly higher for early responders compared to late/non-responders (EPO 1: 84.0% vs. 46.5%, EPO 2: 79.1% vs. 49.1%, EPO 3: 79.8% v. 43.6%; all p<0.0001). Conclusions: Early response with EPO compared to late/non-response was associated with statistically higher changes in QoL, lower transfusion use and higher hemoglobin response by EOS regardless of QW or TIW EPO administration. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech Products, L.P. Ortho Biotech Products, L.P. Ortho Biotech Products, L.P.

Evaluation of the relationship between early hemoglobin rise during epoetin alfa treatment and improved patient-reported quality of life

8124 Background: Previous research has confirmed epoetin alfa (EPO) improves quality of life (QoL) in patients with chemotherapy-related anemia. This analysis evaluates the association between an early hemoglobin (Hb) rise during EPO treatment and patient-reported QoL. Methods: Data from two EPO trials were used (Study 1: N=2,964; Study 2: N=2,289). EPO regimens were: Study 1: 40,000U once weekly; Study 2: 10,000U thrice weekly. Treatment duration for both trials was 16 weeks. Patients were at least 18 years old, had a baseline Hb of less than or equal to 11 g/dL, and received concomitant chemotherapy. Early Hb rise was defined as Hb change at week 4 of EPO therapy independent of transfusion. Change in QoL was measured at week 8 and end of study (EOS) by the Linear Analog Scale Assessment and Functional Assessment of Cancer Therapy -Anemia and Fatigue. Multivariate analyses were conducted to isolate the effect of early Hb rise on change in QoL while controlling for the following covariates: baseline QoL, change in Hb after week 4, age, gender, tumor type, baseline Eastern Cooperative Oncology Group (available for Study 1) score, tumor response, and receipt of platinum chemotherapy. Results: Mean change in Hb (g/dL) observed at week 4 were similar across studies ([On-treatment; week 4, Study 1:1.0, Study 2: 1.2]; [Intent-to-treat; week 4, Study 1: 0.8, Study 2: 0.9]). Multivariate analyses revealed a significant association between early Hb rise and change in QoL at both week 8 and EOS, consistently observed across all QoL parameters, patient populations, and studies (all p< 0.0001). Furthermore, the magnitude of early Hb rise effect on QoL was similar for the on-treatment and intent-to-treat populations. Other covariates consistently observed to be associated with QoL change included: baseline QoL score and tumor response. Conclusions: Early Hb rise during epoetin alfa treatment is significantly associated with improved patient reported QoL. Traditional EOS efficacy measures may not reflect the early benefits of EPO therapy. An erythropoietin that provides an early and sustained Hb rise would be clinically most desirable. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech Products, L.P. Ortho Biotech Products, L.P. Ortho Biotech Products, L.P.

Epoetin alfa maintains ribavirin dose in HCV-infected patients: a prospective, double-blind, randomized controlled study

Background & Aims : Combination therapy with interferon α (IFN-α) and ribavirin (RBV) or pegylated IFN-α (PEG-IFN-α)/RBV for chronic hepatitis C virus (HCV) infection often causes anemia, prompting RBV dose reduction/discontinuation. This study assessed whether epoetin alfa could maintain RBV dose, improve quality of life (QOL), and increase hemoglobin (Hb) in anemic HCV-infected patients. Methods : HCV-infected patients (n = 185) on combination therapy who developed anemia (Hb ≤ 12 g/dL) were randomized into a U. S. multicenter, placebo-controlled, clinical trial of epoetin alfa, 40,000 U subcutaneously, once weekly vs. matching placebo. The study design used an 8-week, double-blind phase (DBP) followed by an 8-week, open-label phase (OLP), in which placebo patients were crossed over to epoetin alfa. Results : At the end of the DBP, RBV doses were maintained in 88% of patients receiving epoetin alfa vs. 60% of patients receiving placebo ( P < 0.001). Mean QOL scores at the end of the DBP improved significantly on all domains of the Linear Analog Scale Assessment (LASA) and on 7 of the 8 domains of the Short Form-36, version 2 (SF-36v2). Mean Hb increased by 2.2 ± 1.3 g/dL (epoetin alfa) and by 0.1 ± 1.0 g/dL (placebo) in the DBP ( P < 0.001). Similar results were demonstrated in patients who switched from placebo to epoetin alfa in the OLP. Epoetin alfa was well tolerated; the most common adverse effects were headache and nausea. Conclusions : Epoetin alfa maintained RBV dose and improved QOL and Hb in anemic HCV-infected patients receiving combination therapy.

Epoetin alfa in patients not on chemotherapy – Canadian data

A prospective open-label study was designed to evaluate the safety, efficacy, and impact on quality of life of recombinant human erythropoietin (rHuEPO, epoetin alfa) therapy for cancer-related anemia. Of the 401 patients enrolled at 34 centers from across Canada, a cohort of 183 patients did not receive chemotherapy during the 16-week study period. All patients received epoetin alfa 150 IU/kg subcutaneously 3 times per week. The dose was increased to 300 IU/kg if the hemoglobin level did not increase by at least 1.0 g/dL after 4 weeks. Epoetin alfa therapy significantly increased hemoglobin levels and reduced transfusion requirements. Moreover, epoetin alfa provided statistically significant and clinically meaningful improvements in quality of life as measured by the Functional Assessment of Cancer Therapy–Anemia and Linear Analog Scale Assessment (also known as Cancer Linear Analog Scale). Increases in hemoglobin were correlated significantly with improvements in quality of life as well as Eastern Cooperative Oncology Group performance status. Treatment with epoetin alfa was well tolerated. These results demonstrate that epoetin alfa therapy is effective and safe in cancer patients with anemia, regardless of whether they are or are not receiving chemotherapy. Semin Oncol 29 (suppl 8):75-80. Copyright 2002, Elsevier Science (USA). All rights reserved.

The use of epoetin alfa in chemotherapy patients: A consistent profile of efficacy and safety

Epoetin alfa has been in use for over a decade to increase hemoglobin in patients with cancer who develop chemotherapy-associated anemia. Early placebo-controlled, randomized studies, as well as recent large, community-based trials in thousands of patients, have consistently shown recombinant human erythropoietin (rHuEPO, epoetin alfa) to be effective and safe in the treatment of chemotherapy-associated anemia. Patients experienced an improved quality of life (QOL) related to the magnitude of the hemoglobin increase. As measured by a Linear Analog Scale Assessment, mean energy level, ability to do daily activities, and overall QOL improved significantly in patients who received epoetin alfa. The improvement in QOL was similar when anemia-specific instruments (Functional Assessment of Cancer Therapy-Anemia) were used. A large community-based trial has demonstrated that the more convenient once-weekly dosing schedule resulted in good efficacy and safety profiles. A recent double-blind placebo-controlled study that compared the efficacy of epoetin alfa versus placebo in patients receiving nonplatinum-based chemotherapy has confirmed epoetin alfa's efficacy, safety, and beneficial QOL effects. These findings should challenge current anemia management practices and encourage aggressive treatment of anemia in cancer patients receiving chemotherapy. Semin Oncol 29 (suppl 8):81-87. Copyright 2002, Elsevier Science (USA). All rights reserved.

The use of epoetin alfa in chemotherapy patients: A consistent profile of efficacy and safety

Epoetin alfa has been in use for over a decade to increase hemoglobin in patients with cancer who develop chemotherapy-associated anemia. Early placebo-controlled, randomized studies, as well as recent large, community-based trials in thousands of patients, have consistently shown recombinant human erythropoietin (rHuEPO, epoetin alfa) to be effective and safe in the treatment of chemotherapy-associated anemia. Patients experienced an improved quality of life (QOL) related to the magnitude of the hemoglobin increase. As measured by a Linear Analog Scale Assessment, mean energy level, ability to do daily activities, and overall QOL improved significantly in patients who received epoetin alfa. The improvement in QOL was similar when anemia-specific instruments (Functional Assessment of Cancer Therapy-Anemia) were used. A large community-based trial has demonstrated that the more convenient once-weekly dosing schedule resulted in good efficacy and safety profiles. A recent double-blind placebo-controlled study that compared the efficacy of epoetin alfa versus placebo in patients receiving nonplatinum-based chemotherapy has confirmed epoetin alfa's efficacy, safety, and beneficial QOL effects. These findings should challenge current anemia management practices and encourage aggressive treatment of anemia in cancer patients receiving chemotherapy.

Managing cancer-related anaemia with epoetin alfa.

Anaemia occurs in a significant number of patients with cancer, and is associated with symptoms of fatigue, dizziness, headache and decreased health-related quality of life. Clinical trials have demonstrated the ability of epoetin alfa to increase haemoglobin concentrations and reduce transfusion requirements in patients with cancer. Data from three large, open-label, community-based trials of >7000 patients, as well as a series of smaller, randomized, placebo-controlled studies, have confirmed the efficacy of treatment with epoetin alfa in patients undergoing chemotherapy. In two of the community-based studies (>2000 patients in each), patients undergoing chemotherapy received epoetin alfa, 150-300 IU/kg or 10,000-20,000 IU, three times weekly. Significant (P<0.01) increases in haemoglobin concentrations and reductions in transfusion rates were seen in both studies. Significant improvements in quality of life were also reported, as measured by the Linear Analogue Scale Assessment and the Functional Assessment of Cancer Therapy-Anaemia. Importantly, the increases in quality of life were independent of tumour response. These findings were also observed in randomized, placebo-controlled studies. The third study, in approximately 3000 patients, evaluated the efficacy of once-weekly dosing, which significantly (P<0.01) increased haemoglobin concentrations, reduced transfusion requirements and improved quality of life. Greater increases in haemoglobin concentration were associated with greater improvements in quality-of-life scores. The safety and efficacy profile of the once-weekly regimen was comparable with that of the three times weekly regimen. Maintaining optimal quality of life, while achieving tumour stabilization or regression, is essential to the successful management of patients with cancer. Epoetin alfa has been shown to increase haemoglobin concentration, decrease transfusion requirements and increase quality of life. Given the frequency of adverse sequelae associated with anaemia, its aggressive management should become an integral and routine part of cancer treatment.

Clinical assessment of HIV-associated lipodystrophy syndrome: bioelectrical impedance analysis, anthropometry and clinical scores

Background: Diagnosis of the HIV-associated lipodystrophy syndrome is based on clinical assessment, in lack of a consensus about case definition and reference methods. Three bedside methods were compared in their diagnostic value for lipodystrophy. Patients and Methods: Consecutive HIV-infected outpatients (n=278) were investigated, 128 of which also had data from 1997 available. Segmental bioelectrical impedance analysis (BIA) and waist, hip and thigh circumferences were performed. Changes in seven body regions were rated by physicians and patients using linear analogue scale assessment (LASA). Diagnostic cut-off values were searched by receiver operator characteristics. Results: Lipodystrophy was diagnosed in 85 patients (31%). BIA demonstrated higher fat-free mass in patients with lipodystrophy but not after controlling for body mass index and sex. Segmental BIA was not superior to whole body BIA in detecting lipodystrophy. Fat-free mass increased from 1997 to 1999 independent from lipodystrophy. Waist-hip and waist-thigh ratios were higher in patients with lipodystrophy. BIA, anthropometry and LASA did not provide sufficient diagnostic cut-off values for lipodystrophy. Agreement between methods, and between patient and physician rating, was poor. Conclusion: These methods do not fulfil the urgent need for quantitative diagnostic tools for lipodystrophy. BIA estimates of fat free mass may be biased by lipodystrophy, indicating a need for re-calibration in HIV infected populations.

Dyspnea: assessment and treatment.

Dyspnea, or breathlessness, is a very distressing and prevalent symptom for patients with terminal cancer. Assessment for this symptom is generally poorly conducted, and it is therefore frequently underdiagnosed and inadequately treated. This paper outlines several tools found in the literature that may be beneficial to us in assessing this symptom. There will also be a full report on the application of these scales as used in a hospital audit of all in-patients at the Queensway- Carleton Hospital in Nepean, Ontario, during the month of June 1995. Results of this hospital audit revealed that 33% of all patients in hospital complained of some degree of breathlessness on both the Linear Analogue Scale Assessment and the Borg Scale. However, when the Modified Medical Research Council Dyspnea Scale and the Oxygen Cost Diagram Scale were used 75.6% and 78.5% respectively now complained of significant shortness of breath interfering with their quality of life. We also found that patients experiencing dyspnea were 39% more likely to complain of other symptoms than patients with no shortness of breath and were 55% more likely to report other symptoms as being severe. A short section will also outline the medical and nursing management of dyspnea and will include a discussion of possibly correcting the cause of breathlessness, environmental issues, and pharmacological management of dyspnea. It is advocated that during the terminal stages of a patient's illness, when assessment tools are no longer feasible or possible, that a "breathing comfortably" approach be adopted for patient and family comfort.

A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis

To evaluate the efficacy of goserelin versus a low-dose cyclic oral contraceptive (OC) in improving pelvic pain in women with endometriosis and to compare recurrence of symptoms during follow-up. Open-label, randomized trial. University hospital endometriosis center. Fifty-seven women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis. Six-month treatment with goserelin depot (n = 29) or a low-dose cyclic OC (n = 28) followed by 6-month follow-up. Variation in severity of symptoms during treatment and at the end of follow-up as shown by a linear analog scale and a verbal rating scale. At 6 months of treatment, a significant reduction in deep dyspareunia was observed in both groups, with goserelin superior to the OC at linear analog scale assessment. Nonmenstrual pain was diminished on both scales without differences between treatments. Women taking the OC experienced a significant reduction in dysmenorrhea. At the end of follow-up, symptoms reappeared without differences in severity between the groups. Low-dose cyclic OCs may be a valuable alternative for the treatment of dysmenorrhea and nonmenstrual pain associated with endometriosis. Symptoms recurred in most subjects 6 months after drug withdrawal.