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© 2001 American Society for Clinical Oncology Epoetin Alfa Therapy Increases Hemoglobin Levels and Improves Quality of Life in Patients With Cancer-Related Anemia Who Are Not Receiving Chemotherapy and Patients With Anemia Who Are Receiving ChemotherapyByFrom the Princess Margaret Hospital; Janssen-Ortho Inc, Toronto; and London Regional Cancer Centre, London, Ontario; Royal Victoria Hospital, Montreal; Hôtel-Dieu de Lévis, Lévis; Hôtel-Dieu de Québec, Québec City, Québec; St John Regional Hospital Facility, St John, New Brunswick; Dr H Bliss Murphy Cancer Center, St John’s, Newfoundland; and British Columbia Cancer Agency, Vancouver, British Columbia, Canada. Address reprint requests to Ian Quirt, MD, Princess Margaret Hospital, Department of Medical Oncology and Hematology, 610 University Ave, Toronto, Ontario, Canada M5G 2M9; email: ian.quirt{at}uhn.on.ca
PURPOSE: To evaluate efficacy, safety, and quality of life (QOL) changes with epoetin alfa therapy for anemia in patients with nonmyeloid malignancies. PATIENTS AND METHODS: Anemic cancer patients were enrolled onto this prospective, open-label study from 34 centers across Canada. The trial had two cohorts: patients who were and were not receiving chemotherapy during the 16-week study. All patients initially received epoetin alfa 150 IU/kg subcutaneously three times per week. The dose was doubled after 4 weeks for patients who did not experience sufficient response. RESULTS: Of the 183 patients enrolled in the nonchemotherapy cohort, statistically significant and clinically relevant improvements in QOL were observed with epoetin alfa therapy using both the FACT-An questionnaire and linear analog scale assessment. Hemoglobin levels increased significantly (P < .001; mean increase 2.5 g/dL from baseline to end of study) and these increases were positively correlated with improved QOL and change in Eastern Cooperative Oncology Group (ECOG) scores. There was a significant reduction in the percentage of patients who required blood transfusions. The 218 patients in the chemotherapy cohort also experienced significant improvements in QOL, decreased transfusion use, and increased hemoglobin levels that correlated with QOL improvements and change in ECOG scores. Epoetin alfa was well-tolerated in both cohorts. CONCLUSION: Epoetin alfa administered to patients with cancer-related anemia for up to 16 weeks resulted in significantly improved QOL, increased hemoglobin levels, and decreased transfusion use. These benefits were observed in cancer patients who were not receiving chemotherapy as well as those who were.
CANCER IS FREQUENTLY associated with significant anemia, either as a result of the disease itself or the effects of cancer treatments (particularly cytotoxic chemotherapy and radiation therapy).1 Although there are several possible causes of anemia in these patients, cancer-related anemia is usually attributable to either direct tumor infiltration of bone marrow or, more commonly, to the anemia of chronic disease (ACD).2 ACD is characterized by mild to moderate erythroid hypoplasia of the bone marrow, a modest decrease in red cell survival, decreased bone marrow reutilization of iron, and inappropriately low serum erythropoietin levels for the degree of anemia.
Erythropoietin is a glycoprotein hormone that is produced primarily in the kidney and acts on bone marrow cells to stimulate RBC production. Epoetin alfa is a glycoprotein manufactured by recombinant DNA technology with an amino acid sequence identical to isolated natural erythropoietin.3 Randomized, placebo-controlled clinical trials were conducted to evaluate the safety and efficacy of epoetin alfa in three groups of patients with cancer-related anemia: those not receiving chemotherapy (118 assessable patients), those receiving chemotherapy that did not include cisplatin (153 assessable patients), and those receiving cisplatin-containing chemotherapy (125 assessable patients).4-6 Epoetin alfa therapy reduced transfusion use and increased hematocrit (after the first month of therapy) in patients receiving chemotherapy. Patients in the nonchemotherapy trial also experienced significant increases in hematocrit, but the decreased transfusion use did not reach statistical significance. It is noteworthy that the patients who did not receive chemotherapy were treated with epoetin alfa 100 IU/kg subcutaneously three times per week for up to 8 weeks, whereas patients receiving chemotherapy trials were treated with a 150-IU/kg dose three times per week for 12 weeks. It was suggested that nonresponders in the nonchemotherapy trial might have benefited from further dose escalation.4 When quality-of-life (QOL) parameters (100-mm linear analog scale assessment [LASA]) were analyzed from all three studies, significant improvements were found in epoetin alfa-treated patients whose hematocrit increased Recent publications have noted that the impact of symptomatic anemia on QOL is of particular concern in patients with cancer, and they emphasize that one of the clinician’s major objectives should be to improve patient QOL.2,7 Fatigue is one of the cardinal symptoms of anemia. It is a highly prevalent condition among cancer patients and is associated with significant functional morbidity, distress, and poor QOL.7,8 The negative effect of fatigue on patient QOL is comparable to that of pain.7 A recent survey asked cancer survivors who had previously undergone chemotherapy what side effect affected them most after completion of chemotherapy. Fatigue was the primary complaint.9 Of the 379 patients who responded to the survey, 76% reported experiencing fatigue (defined as a general feeling of debilitating tiredness or loss of energy) at least once a week; 91% said that it prevented them from leading a normal life, and 88% reported that it altered their daily routine. Similarly, a Canadian survey of 913 cancer patients who had received treatment within the previous 2 years indicated that fatigue (78%) and anxiety (77%) were the most common symptoms associated with cancer and that fatigue was the most debilitating symptom.10 The current prospective study was designed to assess QOL and the efficacy and safety of epoetin alfa therapy in a large cross section of patients with cancer-related anemia in the Canadian clinical practice setting. To reflect standard practice, patient selection and dosing criteria followed the recommendations for the treatment of anemia in cancer patients listed in the Canadian Eprex product monograph. Epoetin alfa therapy is indicated for the treatment of anemia in patients with nonmyeloid malignancies when anemia is a result of the disease itself or the effect of concomitantly administered chemotherapy. Patient selection for the trial, therefore, included two cohorts of patients: those who were not receiving chemotherapy (anemia as a result of the disease itself) and patients who were receiving concomitant chemotherapy. The nonchemotherapy cohort is of particular interest because the study used a higher dose of epoetin alfa for a longer duration than the previous placebo-controlled study5 and prospectively collected tumor response data. In addition, QOL data was assessed in this population using the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale, as well as the LASA used in previous clinical trials. The FACT-An is a validated questionnaire that has a core component addressing general QOL issues plus additional questions that specifically assess fatigue and anemia-related concerns in people with cancer.11,12
Patient Selection and Ethics The inclusion criteria for the study required that patients have nonmyeloid malignancy, with or without concomitant chemotherapy, and symptomatic anemia or a baseline hemoglobin  11 g/dL. The life expectancy for these patients had to be greater than 6 months, and all participants were required to provide written informed consent before entering onto the trial. Patients could be male or female, but females had to be postmenopausal (for at least 1 year) or surgically sterile, or, if of child-bearing potential, had to be practicing an acceptable method of birth control. Exclusion criteria did not permit the entry of patients with acute leukemia or myelogenous malignancy. Patients enrolled onto the nonchemotherapy group could not have received chemotherapy within 1 month before enrollment and could not receive chemotherapy during the trial. Other forms of cancer treatment, such as radiation and hormonal therapy, were allowed in this group. Any patient with uncontrolled hypertension, uncontrolled angina, active thrombotic process, a history of seizures, or cerebral metastases was also excluded. Participants could not be pregnant or nursing, and they could not have any known hypersensitivity to any component of the study medication, including mammalian cell-derived products and human albumin. Patients could not take anabolic steroid therapy during the study, and their anemia could not be a result of factors other than cancer or chemotherapy (eg, untreated iron or folate deficiencies as per center practice, hemolysis, or gastrointestinal bleeding). Patients could be enrolled onto the study only once. The study was conducted in accordance with the current revision of the Declaration of Helsinki, and local ethics committee approval was obtained before study initiation at each participating site. Each patient signed the informed consent form before study participation.
Trial Design
Study Medication Dosage and Administration If at any time during the study, the patient’s hemoglobin level increased by more than 2 g/dL during a 4-week period, their dose of epoetin alfa was reduced by 25%. If the hemoglobin level ever equalled or exceeded 14 g/dL during the trial, medication was temporarily withheld until the hemoglobin fell below 12 g/dL. Epoetin alfa was then reinstituted at a dose 25% below the previous dose. Even if the epoetin alfa was not restarted in these patients, they were followed-up until the end of the study period. At the beginning of the study, each patient had their iron stores evaluated by serum ferritin and transferrin saturation laboratory tests. If serum ferritin was less than 100 µg/L or the transferrin saturation was less than 20%, supplemental iron was recommended to increase and maintain iron stores to levels that would adequately support epoetin alfa-stimulated erythropoiesis. The patient’s serum vitamin B12 and folate levels were also assessed at baseline. If deficiencies existed, appropriate therapy was initiated.
Efficacy, QOL, and Safety Assessments The effect of epoetin alfa therapy on patients’ QOL was a major component of the study and was assessed using two different measures: the LASA tool and the FACT-An (Version 3) self-administered questionnaire. Both methods of assessment have previously been tested and validated in cancer patients.11-14 The LASA tool contains three 100-mm linear-analog scales. Patients were asked to place a mark on the scale to indicate how they felt regarding their energy level, ability to do daily activities, and overall QOL during the previous week. Energy level and ability to do daily activities were scored between as low as could be and as high as could be. Overall QOL was rated between worst possible and best possible. The FACT-An is a questionnaire that assesses fatigue and anemia-related concerns in people with cancer. It contains 49 questions that are scored on a five-point scale (not at all, a little bit, somewhat, quite a bit, very much). The foundation of the FACT-An is the Functional Assessment of Cancer Therapy–General (FACT-G) questionnaire. FACT-G includes 29 questions that measure four general aspects of well-being (physical, social/family, emotional, and functional well-being) and the patient’s relationship with the doctor. An additional 20 questions were developed for the FACT-An to assess the impact of fatigue and other anemia-related symptoms. This 20-question Anemia subscale includes 13 questions specifically related to fatigue (the Fatigue subscale) plus seven additional questions related to anemia but distinct from fatigue. The ECOG performance scale was completed by the investigator at study entry and when the patient completed/discontinued the study. Transfusion requirements were evaluated as the change from baseline in the percentage of patients transfused each month over the course of the study. Any patient who had received at least one blood transfusion in the month before study entry was included in the baseline value. Any patient who received at least one transfusion between the start of the study and the week 4 visit was included in the percentage calculated for month 1. Similarly, the percentage of patients requiring blood transfusions was calculated for month 2, month 3, and month 4. Changes in the number of units of blood transfused each month were also assessed. Safety was assessed through adverse event reporting and the monitoring of vital signs and laboratory parameters.
Statistics Changes from baseline for hemoglobin levels, number of units of blood transfused, and QOL scores (LASA and FACT-An scales) were analyzed by paired t-test. Analyses of QOL scores included patients with both baseline and final assessments. Pearson’s correlation coefficients between increases in hemoglobin and increases in QOL measures and ECOG performance score were obtained. Logistic regression analyses were performed to explore the relationship between responders and potential predictors of response.
Patients were enrolled onto the study by hematologists and oncologists at 34 cancer centers across Canada. Each center enrolled six to 30 patients.
Nonchemotherapy Cohort
The mean age of the nonchemotherapy patients was 65.1 years, and 46% were female. The majority of the cancers in the nonchemotherapy cohort were nonhematologic and metastatic (Table 2), and patients had a mean of 3.4 years since diagnosis. Two thirds of the nonchemotherapy cohort had previously received at least one regimen of chemotherapy, and 43% of them had received at least one previous radiation treatment. The mean times of chemotherapy and radiation treatment to epoetin alfa therapy were 9 ± 15 months (median, 4 months; range, 0 to 129 months) and 21.7 ± 51.4 months (median, 8 months; range, 0 to 361 months), respectively. Radiation therapy was given to 15% of the patients during the study for a mean of 11 days. Of the 183 patients enrolled, 8% received hormonal cancer therapy, 4% received biologic response modifiers, and 2% received aromatase inhibitors during the study.
Low iron stores were defined as serum ferritin less than 100 µg/L or transferrin saturation less than 20%. In the nonchemotherapy group, 43% of the patients had low iron stores at study entry, 34% of the patients received iron supplementation during the study, and, for those patients who continued until the final month of the study, 22% continued to have low iron stores. The dose of epoetin alfa was doubled to 300 IU/kg for 39% of the nonchemotherapy patients, and the mean time to this dose increase was 5 weeks. The mean duration of treatment with epoetin alfa for all nonchemotherapy patients was 10.7 weeks. In accordance with the protocol, approximately one fifth (21%) of patients had their dose of epoetin alfa withheld because their hemoglobin was more than 14 g/dL (at a mean of 9.3 weeks); 15% of these patients restarted epoetin alfa at a dose 25% below their prior dose. Hemoglobin levels. Hemoglobin levels were measured throughout the trial, and significant increases were observed for the nonchemotherapy patients over the course of the study (Fig 1). The mean baseline hemoglobin was 9 g/dL, and 1 week after initiation of epoetin alfa therapy, patients had a significant mean 0.3 g/dL increase from baseline (P < .001), reaching an increase of 1.1 g/dL by week 4. Hemoglobin levels continued to increase over the course of the study to reach a maximum after 3 to 4 months of epoetin alfa therapy. The nonchemotherapy patients had a mean 2.5 g/dL increase in hemoglobin levels (P < .001) from baseline to the end of the 16-week study. There were 84 patients who completed the trial and had this week-16 hemoglobin value.
Responders to epoetin alfa therapy were defined as patients who experienced an increase in hemoglobin of  2 g/dL during the study without the benefit of a transfusion within the previous 4 weeks. In the nonchemotherapy cohort, 48% of the 182 cancer patients fulfilled the criteria as hemoglobin responders. For the 169 patients who completed at least 4 weeks of epoetin alfa therapy, 52% were responders.
To evaluate any predictive value of hemoglobin levels as an indicator of eventual response, the proportion of responders and nonresponders was calculated for patients who experienced increases in hemoglobin levels QOL measures. QOL was assessed at the beginning of the study and again at the end of the study using two different tools: three LASA questions and the FACT-An questionnaire. Overall, data collected with the FACT-An questionnaire correlated with the data collected with the LASA instrument. LASA. The mean baseline scores for the three LASA questions are indicative of this population perceiving substantial limitations to their QOL: energy level = 34 mm, daily activities = 36 mm, and overall well-being = 41 mm. By the end of the study, all the scores showed statistically significant improvement (P < .001) (Fig 2). When LASA was compared with the questions in FACT-An related to physical experience of fatigue, a change in score of more than 10 mm correlated to a 22% increase in energy level (one level change in the Likert scale). Thus, the 11-cm increase in score after epoetin alfa treatment reflects clinically meaningful improvement.11,15-18
There was a notable difference in mean LASA change-scores between hemoglobin responders and nonresponders. This was particularly evident for the measure of daily activities and the overall assessment, both of which actually worsened for nonresponders. The association between hemoglobin levels and QOL was reflected in the significant positive correlation between change in LASA and change in hemoglobin: energy level (r= 0.30, P = .001), daily activities (r= 0.29, P = .002), and overall well-being (r= 0.25, P = .009). FACT-An. Scores for the total 49-item FACT-An also showed significant improvement for patients in the nonchemotherapy cohort (P < .002) (Fig 3). A recent publication indicated a change in score of 2.25 in FACT-G and 4.22 in FACT-An fatigue corresponding to Minimum Clinical Important Differences. The mean 2.5 point increase in FACT-G and 8.8 point increase in FACT-An score after epoetin alfa therapy exceeded the change required to reflect a significant improvement in QOL.17 Components of the FACT-An were also evaluated separately. Significant improvement from baseline was observed in the 20-question anemia subscale (P < .001). The change in scores for the more general FACT-G questions approached statistical significance for the nonchemotherapy group (P = .057). The fatigue subscale, which comprises 13 fatigue-specific questions within the anemia subscale, showed a significant 21% improvement from baseline after epoetin alfa therapy (P < .001).
As with the LASA data, the FACT scales revealed a marked difference between the results for responders and nonresponders (Fig 3). Statistically significant and clinically relevant changes in mean score were observed for all FACT scales in the responder group, although none of the scores changed significantly for the nonresponders. Nonresponders showed a slight worsening in QOL compared with baseline. The association between an increase in hemoglobin levels and an increase in QOL was confirmed by a significant correlation between the change in the FACT-An and the change in hemoglobin for the nonchemotherapy group (r= 0.33, P < .001). This correlation was also demonstrated separately for the components of the FACT-An, including the FACT-G (r= 0.26, P = .006) and the anemia (r= 0.34, P < .001) and fatigue (r= 0.22, P = .017) subscales. ECOG performance status scores and tumor response. ECOG performance status was measured at the beginning of the trial and again at the end of the study. At baseline, 57% of patients had a score between 0 and 1 (fully active to restricted in strenuous activity). At study termination, 46% of the nonchemotherapy patients had a score between 0 to 1. Overall, the change in status from baseline to the final visit worsened for 48% of patients, remained the same for 31%, and improved for 20% of the nonchemotherapy cohort. A significant correlation was observed between change in hemoglobin level and change in ECOG scores (r= -0.33, P = .0001). Therefore, changes in hemoglobin levels had a similar effect on ECOG performance status as noted with the LASA and FACT-An QOL measures. As assessed by physician judgment, 51% of the patients in the nonchemotherapy cohort showed signs of progressive disease relative to baseline at the end of the trial. Transfusion requirements. There was a significant reduction in the percentage of patients who received transfusions over the course of the study (Table 3). In the month before study initiation, 29% of the 182 patients in the nonchemotherapy group had received at least one blood transfusion. After 2 months of epoetin alfa therapy, there was a statistically significant reduction (P < .02) in the percentage of patients who required transfusions (19% of 166 patients). Only 8% of 101 patients received transfusions during the final month of the 16-week study (P < .001).
Correspondingly, the mean number of units of blood transfused dropped from 0.79 units per patient assessed in the month before study start to 0.22 units per patient assessed in the final month of the study (P < .01). For patients who required transfusion, mean units per transfusion remained between 2.7 and 3.1 units throughout the study. Safety. All 183 patients enrolled onto the nonchemotherapy group were included in the safety analysis. Any adverse events reported by at least 5% of the patients are listed in Table 4. The corresponding proportion of these events that were assessed by the investigator as possibly, probably, likely, or certainly related to the study drug are also provided in Table 4.
Most adverse events were not considered to be related to the study medication. Serious adverse events that the investigator assessed as possibly or probably related to the study drug were reported for only six patients (3%) in the nonchemotherapy cohort. No new or unexpected serious adverse events were observed. There were 28 deaths in the nonchemotherapy group during the trial (15% of patients), despite the entry criteria of life expectancy of greater than 6 months. Most deaths resulted from progressive disease, and none were considered related to study drug. No clinically significant changes in vital signs (pulse, blood pressure), weight, or consistent changes in laboratory tests (platelet or neutrophil counts) were observed.
Chemotherapy Cohort
Assessment of disease response at the end of the study revealed 32% of patients with progressive disease, 23% with stable disease, 29% with partial response, and 15% with complete response. From baseline to the final visit, ECOG status worsened for 34%, remained the same for 42%, and improved for 23% of the chemotherapy patients. Low iron stores were reported for 29% of the patients at study entry, and 28% of patients received iron supplementation during the study. At the end of the study, 22% of the patients had low iron stores. Epoetin alfa dose was doubled to 300 IU/kg for 39% of the chemotherapy patients at a mean of 5 weeks into the study. Hemoglobin levels. Mean hemoglobin levels increased a significant 2.8 g/dL from baseline to the end of the study, and 63% of the chemotherapy cohort fulfilled the criteria for responders to epoetin alfa. If patients experienced at least a 1 g/dL increase in hemoglobin during the first 4 weeks of the study, then 84% were responders by the end of the study. Even if the hemoglobin increase was less than 1 g/dL in the first 4 weeks, 47% of these patients eventually became responders during the study. This suggests that the continuation of epoetin alfa therapy can provide benefit to a substantial proportion of these patients. QOL measures. QOL measures demonstrated statistically significant and clinically relevant improvements for all three LASA scores (energy, activities, and overall well-being) (Fig 4). Scores for the FACT-An and its components also showed significant improvement from baseline to the end of the study (Fig 5). The improvements in QOL were positively correlated with the increase in hemoglobin for the FACT-An and its components. Similar to QOL improvements, ECOG scores also showed a significant correlation with hemoglobin change (r= -0.24; P = .0003).
Transfusion use. Transfusion requirements decreased significantly from 34% of 218 patients receiving at least one blood transfusion in the month before study entry to 19% of 206 patients during the second month of treatment (P < .001). During the fourth and final month of the study, transfusion rates dropped to 9% of 153 patients (P < .0001). There was also a significant decrease in the mean number of units of blood transfused per patient per month over the course of the study. Safety. As reported previously, no serious drug-related adverse events were observed during epoetin alfa treatment.
In addition to the significant results reported from initial placebo-controlled trials,4-6 the positive effect of epoetin alfa on QOL (correlated with increases in hemoglobin) and reducing transfusion requirements in anemic cancer patients receiving chemotherapy has been confirmed in two recent, large, open-labeled trials.18,19 Although chemotherapy is the standard treatment for most malignancies, the population of cancer patients who are not receiving chemotherapy can also suffer the effects of anemia. This study investigated the effect of epoetin alfa on cancer patients not receiving chemotherapy. Except for the subset of patients (14%) receiving other forms of cancer treatment (ie, hormone therapy, biologic response modifiers, and aromatase inhibitors), the majority of patients did not receive active treatments. The mean time since last chemotherapy and radiation treatment for this group was 9 and 22 months, respectively, which suggests that anemia was unlikely to have been a result of treatment. These patients suffered from ACD, and the burden of cancer was the primary reason for their anemia. One placebo-controlled study has previously evaluated epoetin alfa in this nonchemotherapy population, but it used a lower dose and duration of therapy than that used in studies with patients who were receiving chemotherapy.4 In addition, the previous placebo-controlled studies did not collect prospective disease response data and only used the LASA to assess changes in QOL. The current study included a nonchemotherapy cohort of patients in whom QOL was evaluated with two validated instruments: the previously tested LASA and the FACT-An questionnaire. The recent addition of FACT-An to the armamentarium of QOL questionnaires allows the assessment and interpretation of the impact of anemia on QOL in cancer patients. In addition, tumor response data were collected prospectively, and a more appropriate dosing regimen, comparable with that used for chemotherapy patients, was studied. The data provided the basis to fully profile the effects of epoetin alfa on QOL parameters, hemoglobin response, and transfusion requirements in the context of disease progression for anemic cancer patients who did not receive chemotherapy. Results from the current study revealed that nonchemotherapy patients experienced significant improvements in their QOL with epoetin alfa therapy, with a mean increase in FACT-An score of 8.8 (P < .001) from baseline to the end of treatment. Responders, or erythropoietin-sensitive patients, responded more dramatically, with a mean increase in FACT-An score of 15.5. Similarly, significant increases were reported for subscales of the FACT-An, including the anemia subscale and particularly the fatigue subscale, reflecting the fact that fatigue is one of the hallmark symptoms of anemia. All three LASA scores (energy levels, daily activities, and overall well-being) also showed significant improvements from baseline to study end. As observed with the FACT-An scores, these improvements in LASA scores were directly and positively correlated with increases in hemoglobin levels. From baseline to study end, the changes observed in the FACT-An and LASA scores for the nonchemotherapy patients were comparable with the results reported for chemotherapy patients in the two large open-label studies,18,19 which confirmed that epoetin alfa was similarly effective in enhancing functional capacity and energy level in nonchemotherapy patients. ECOG performance scores were collected prospectively at baseline and at the end of study. Although overall scores did not change significantly, a significant correlation between increase in hemoglobin level and improvement in ECOG scores was observed. This improvement in the functional capacity of nonchemotherapy cancer patients mirrored the improvement in QOL parameters. The number of patients enrolled onto the nonchemotherapy cohort was too small to statistically evaluate the impact of disease progression on response to epoetin alfa, but in patients with significant disease progression, a high proportion responded to epoetin alfa. The nonchemotherapy cohort also experienced decreased transfusion requirements with epoetin alfa therapy. Although the decreased transfusion requirements did not reach statistical significance with the 100-IU/kg dose used in the previous placebo-controlled study,5 with the more appropriate dosing regimen used in the current study (150 IU/kg), a significant reduction in transfusion use was achieved by the second month, and transfusion use continued to decrease over the entire course of the study.
Predicting the responsiveness of cancer patients to epoetin alfa therapy is an important medical issue for the treating clinician. Previous studies with patients on chemotherapy used a In addition to the nonchemotherapy data collected in this study, data from a cohort of 218 chemotherapy patients were also collected. Increases in hemoglobin, improvement in QOL parameters, and reduction in transfusion requirements observed in this study were similar to previous observations.18,19 In addition, hemoglobin levels as a predictor of response continued to be a useful indicator. The results for the chemotherapy group are not discussed in detail here. Patients with cancer-related anemia can benefit significantly from epoetin alfa therapy whether they are receiving chemotherapy or not. As observed in previous trials, epoetin alfa was well-tolerated in both cohorts of patients assessed in our trial. This current trial demonstrated that cancer patients treated with epoetin alfa derived significant improvements in QOL, increased hemoglobin levels, and a reduction in transfusion use. These benefits were seen across all tumor types. Directions for future clinical trials include studying the optimal use of epoetin alfa in tumor-specific settings, with or without the confounding effects of chemotherapy.
The following investigators and study nurses/coordinators contributed to and enrolled patients onto this study: Hakam Abu-Zahra, MD, Barbara Adamska, Faye Aspelund, Lorna Beairsto, Julie Becevel, Robert Bélanger, MD, Mario Bélanger, MD, Phyllis Bettello, Claire Bouchard, Joseph Brandwein, MD, Susan Burdette-Radoux, MD, Ronald Burkes, MD, José Chang, MD, Kim Chenier, Penny Chipman, Lise Claprood, Félix Couture, MD, Jane Cowan, Sean Dolan, MD, Yvan Drolet, MD, Jean Dufresne, MD, Pat Dupuis, Crystal Fietz, Brian Findlay, MD, Sheldon Fine, MD, Françoise Gagnon, John Gapski, MD, Hélène Goulet, Martin Gyger, MD, Francine Habel, Danielle Hallé, Rashida Haq, MD, Wanda Hawryluk, Pat Henderson, Joanne Hewitt, Susan Huan, MD, Kevin Imrie, MD, Theresa Jones, Michael King, MD, Paul Klimo, MD, Michael Kovacs, MD, Maria Laamanan, Francis Laberge, MD, Tracy Lam, André Lavoie, MD, Marilyn Leighton, Marilyn Lockyer, Pedro Lopez, MD, Allene MacIsaac, Pat MacDonald, Andrew Maksymiuk, MD, Mary Mandel, Danièle Marceau, MD, Heidi Martins, MD, Michael McKenzie, MD, Sheila McRae, Jean-Pierre Moquin, MD, Isabelle Nadeau, Pierre Ouellet, MD, Martin Palmer, MD, Lynda Phippard, Ian Quirt, MD, Joseph Ragaz, MD, Sandra Rayson, MD, Kathie Roche, Roanne Segal, MD, Hervé Simard, MD, Raynald Simard, MD, Sylvana Spadafora, MD, Terence Sparling, MD, David Stewart, MD, Carolle St-Pierre, Kathleen Tan, Shou-Ching Tang, MD, Nicole Tassé, Darlene tenHaaf, Claude Tessier, MD, John Trachtenberg, MD, Sharon Turnell, Cheryl Upright, Dimitrios Vergidis, MD, David Walde, MD, Brenda Waterfield, David White, MD, Daphne Willan, Eric Winquist MD, Louise Yelle, MD.
Supported by Janssen-Ortho Inc, Toronto, Ontario, Canada.
All trademark rights used under license. Eprex is also marketed as Procrit (Ortho Biotech Inc, Raritan, NJ).
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Copyright © 2001 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
; nonchemotherapy cohort, 
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