A new induction schedule of epoetin alfa 40.000 IU in anemic patients with advanced lung cancer

BACKGROUND: Non-small cell lung cancer (NSCLC) treatment with new drugs in combination with platinum salts induce anemia G1/2 and G3/4 WHO in about 35 and 10-20% of patients, respectively, with a chemotherapy (CT) dose intensity decrease in 20% of cases. Epoetin alfa, administered at standard dosages has been shown to significantly increase hemoglobin (Hb) levels, decrease transfusion requirements, and improve quality-of-life parameters in patients undergoing chemotherapy. OBJECTIVE: This open-label, non-randomized study was conducted to evaluate the efficacy and safety of an induction dose of epoetin alfa 40.000 IU in lung cancer patients with moderate or severe anemia who were receiving CT. PATIENTS AND METHODS: Twenty-four patients (8 SCLC and 16 NSCLC) were enrolled in the study to receive single subcutaneous (s.c.) injections of epoetin alfa 40.000 IU on days 1, 4, 7, 10, and 13, followed by standard treatment (10.000 IU t.i.w.) for the further 2 weeks. Nine patients had been previously treated with epoetin alfa 10.000 IU t.i.w. Twenty-two patients were receiving first-line CT and two patients were receiving docetaxel as second-line CT. RESULTS: After 15 days of treatment, in 21 evaluable patients, Hb was 10.5 +/- 1.3 g/dL (mean +/- S.D.), with a mean increase from baseline of 2.0 g/dL (95%CI: 1.3-2.7). Hb increase was > or =2g/dL in 11 patients, 1-1.9 g/dL in 5 patients, and <1g/dL in 5 patients. After 30 days of treatment, Hb was 11.5 +/- 0.8 g/dL (mean +/- S.D.), with a mean increase from baseline of 2.9 g/dL (95%CI: 2.4-3.4) in 20 evaluable patients. No adverse events possibly related to epoetin alfa treatment were observed. CONCLUSION: An induction therapy with epoetin alfa 40.000 IU for 2 weeks followed by standard treatment allows an Hb increase of 2.9 g/dL even in advanced lung cancer patients with a moderate/severe anemia, without RBC transfusion requirements. A randomized study of the proposed induction dose of epoetin alfa 40.000 IU is actually ongoing.     

Once-weekly epoetin beta (30,000 IU) in anemic patients with lung cancer receiving chemotherapy

Anemia occurs frequently in patients with lung cancer receiving chemotherapy and has a negative impact on quality of life (QoL). Erythropoietic proteins effectively increase hemoglobin (Hb) levels, reduce transfusion requirements and improve QoL in anemic patients with a range of malignancies. This prospective, observational study evaluated epoetin beta 30,000 IU once weekly in patients with lung cancer in a real-life, clinical-practice setting. Forty patients (72.5% with NSCLC and 27.5% with SCLC) were treated with epoetin beta during any cycle of chemotherapy when Hb decreased to <12 g/dL. Hb levels were assessed at regular intervals and transfusion needs were monitored throughout the study. In total, 72.5% of patients required epoetin treatment by the second cycle of chemotherapy. Epoetin beta treatment duration ranged from 1 to >9 (median 4) weeks. Mean (+/-S.D.) baseline Hb was 10.4+/-1.2 g/dL. Epoetin beta was associated with a rapid increase in Hb levels, with a mean increase of 1.3 g/dL by week 4. Most patients (95%) remained transfusion-free throughout the study. Epoetin beta was well tolerated. This early intervention strategy with epoetin beta 30,000 IU once weekly is an effective and well-tolerated therapy for anemia in patients with lung cancer.     

Patients previously transfused or treated with epoetin alfa at low baseline hemoglobin are at higher risk for subsequent transfusion: an integrated analysis of the Canadian experience

BACKGROUND: The introduction of recombinant human erythropoietin to the management of anemia in cancer patients has resulted in significant reductions in allogeneic blood transfusions, while at the same time contributing to improvements in quality of life. A recent meta-analysis of five randomized, placebo-controlled trials with patient-level data revealed that, while epoetin alfa was very effective in reducing transfusions compared with placebo, patients who were pretransfused were twice as likely to subsequently be transfused during epoetin alfa treatment. METHODS: To further assess the validity of this rather provocative concept, another integrated analysis was conducted with patient-level data from three Canadian trials, with a combined total of 665 patients receiving epoetin alfa treatments for their cancer- and chemotherapy-induced anemia. RESULTS: Once again, pretransfusion was the most significant baseline predictor of transfusion, with patients that were pretransfused having a significantly greater likelihood of being transfused than their transfusion-naive counterparts. Furthermore, and corroborating previous findings, baseline hemoglobin (Hb) level was again found to be a significant predictor of transfusion, with patients who were treated at a baseline Hb level < 10 g/dl having a higher chance of being transfused than patients in whom epoetin alfa was initiated at baseline Hb levels of 10-11 g/dl. In addition, when the total units transfused in patients receiving epoetin alfa at different baseline Hb levels were analyzed, >85% of the units of blood transfused were received by patients with baseline Hb levels < 10 g/dl. CONCLUSION: These data strongly suggest that early treatment with epoetin alfa could significantly optimize clinical benefit in reducing the use of transfusion in cancer patients receiving chemotherapy.     

Epoetin alfa in platinum-treated ovarian cancer patients: results of a multinational, multicentre, randomised trial

This multicentre, open-label, controlled clinical trial assessed the effects of epoetin alfa treatment on haematologic and quality of life (QOL) parameters in 182 anaemic (Hb< or = 12 g dl(-1)) ovarian cancer patients receiving platinum chemotherapy. Patients were randomised 2 : 1 to receive epoetin alfa 10,000-20 000 IU three times weekly plus best standard treatment (BST) or BST only. Main study end points were changes from baseline in haemoglobin (Hb) level, transfusion requirements, and QOL. For the epoetin alfa group, mean Hb increased by 1.8 g dl(-1) by weeks 4-6 and was significantly increased from baseline through study end (P<0.001). The mean change in Hb from baseline was significantly (P<0.001) greater for epoetin alfa than BST patients at all post-baseline evaluations. Significantly fewer epoetin alfa than BST patients required transfusion(s) after the first 4 weeks of treatment (7.9 vs 30.5%; P<0.001). Also, significant (P< or = 0.04) differences favouring the epoetin alfa group over the BST group were found for all three median CLAS scores (Energy Level, Ability to Do Daily Activities, Overall QOL) and the median average CLAS score during chemotherapy. These findings support use of epoetin alfa to increase Hb levels, reduce transfusion use, and improve QOL in anaemic ovarian cancer patients receiving platinum chemotherapy.     

Standard of care for cancer-related anemia: improving hemoglobin levels and quality of life

The introduction of recombinant human erythropoietin (rHuEPO) has proven to be a major advance in the therapeutic options available for managing anemia in cancer patients. The results of placebo-controlled clinical trials and large, community-based, open-label studies have confirmed that epoetin alfa, a recombinant human erythropoietin, significantly reduces transfusion requirements, and reliably increases hemoglobin (Hb) levels in anemic (Hb level <12 g/dl) cancer patients undergoing chemotherapy. Increased Hb improves patients' energy level and their ability to perform the activities of daily living, as well as their overall quality of life (QOL). These findings are independent of tumor type and disease status and are comparable in patients receiving nonplatinum- and platinum-based chemotherapeutic regimens. Furthermore, more than a decade of use in clinical trials and by physicians in routine clinical practice has demonstrated that epoetin alfa is safe and well tolerated when used to treat cancer patients with anemia. The availability of epoetin alfa as an alternative to transfusion has changed practices in anemia management; physicians can now treat anemia with the goal of achieving adequate Hb levels to relieve anemia-related fatigue, a major symptom contributing to decreased QOL in cancer patients. Incremental benefit analysis has shown that increasing Hb level from 11 g/dl to 12 g/dl yields the greatest improvement in QOL per 1 g/dl increase in Hb. The demonstrated efficacy of epoetin alfa for increasing Hb levels and improving patient QOL have made this agent a rationale choice for management of cancer-related anemia. Ongoing research will continue to provide new insights into best management of anemia with epoetin alfa in cancer patients.     

Effectiveness and safety of an induction therapy with epoetin alfa in anemic cancer patients receiving concomitant chemotherapy

BACKGROUND: Epoetin alfa, administered at standard dosages of 10,000-20,000 IU three times weekly or 40,000-60,000 IU once weekly, has been shown to significantly increase hemoglobin (Hb) levels, decrease transfusion requirements, and improve quality-of-life parameters in patients undergoing chemotherapy.Objective. This open-label, nonrandomized, historically controlled study was conducted to evaluate the efficacy and safety of an induction dose of epoetin alfa in patients with moderate or severe anemia who were receiving chemotherapy. METHODS: Nineteen patients with solid tumors and Hb levels < 9.0 g/dl were enrolled. The patients received single s.c. injections of epoetin alfa, 40,000 IU, on study days 1, 4, 7, 10, and 13, and were then observed for the following 30 days. Nineteen other cancer patients who had matching characteristics and had received epoetin alfa, 10,000 IU, three times weekly for the 45-day study period, served as historical controls. The primary efficacy variable was change in Hb level from baseline to days 15 (approximately week 2) and 45 (approximately week 6.5). Secondary efficacy variables included the percent response (Hb increase > or = 1 g/dl) and percent major response (Hb increase > or = 2 g/dl) at days 15 and 45, the durations of response and major response after day 45, the proportion of patients transfused within the 45 study days, the changes in Eastern Cooperative Oncology Group performance status score at days 15 and 45, and the ability to maintain the planned chemotherapy dose (dose intensity) over the 45-day study. RESULTS: Mean increases in Hb level in the epoetin alfa 40,000 IU group were significantly greater than those in the historical control group both at day 15 and at day 45. The increase in Hb level in the control group approximated increases reported with standard 3-times-weekly epoetin alfa at day 15 but was somewhat lower than the increases typically seen by day 45, presumably due to the fact that, in the present study, the epoetin alfa dose was not doubled in initial nonresponders, as is commonly done with standard epoetin alfa treatment. The rates of major response for epoetin alfa 40,000 IU patients (37% at day 15 and 84% at day 45) were higher than those for control patients (16% and 21%, respectively). Also, the transfusion rate was lower and performance status scores were better in the epoetin alfa 40,000 IU patients than in the control patients. In all, 74% of epoetin alfa 40,000 IU patients versus 47% of control patients received 100% of the planned chemotherapy dose. Epoetin alfa was well tolerated in both treatment groups. CONCLUSIONS: Results of this study suggest that epoetin alfa at a dose of 40,000 IU administered five times over 2 weeks may confer even higher response rates than those seen with standard dosing regimens. These encouraging results support further study of the proposed induction dose of epoetin alfa in a larger, randomized, prospectively controlled trial.     

Epoetin alfa corrects anemia and improves quality of life in patients with hematologic malignancies receiving non-platinum chemotherapy

Anemia, a commonly occurring morbidity in patients with cancer, often leads to diminished quality of life (QOL). Numerous clinical trials have shown that epoetin alfa treatment improves hematologic and QOL variables in cancer patients. The clinical trial analysis reported here was performed to assess response to epoetin alfa in patients with hematologic malignancies. Cancer patients with anemia undergoing non-platinum-based chemotherapy who were enrolled in a multinational, randomized (2:1), double-blind, placebo-controlled trial were prospectively stratified by tumor type (hematologic, solid). Efficacy endpoints included proportion of patients transfused after day 28; change in hemoglobin (Hb) level from baseline to last assessment; proportion of treatment responders (increase in Hb > or =2 g/dl unrelated to transfusion) and correctors (patients whose Hb levels reached > or =12 g/dl during the study); and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study, and survival for the full study cohort was estimated using Kaplan-Meier techniques. Efficacy analyses of hematologic and QOL variables, as well as Kaplan-Meier estimates of survival, were performed post hoc for the hematologic tumor stratum. Among patients with hematologic malignancies, the mean increase in Hb levels was greater with epoetin alfa than with placebo treatment (2.2 vs. 0.3 g/dl). Transfusion requirements were lower in patients who received epoetin alfa versus placebo (25.2 vs. 43.1%), and the proportion of responders and correctors was higher with epoetin alfa than with placebo (75.2 vs. 16.7% and 72.6 vs. 14.8%, respectively). Patients who received epoetin alfa had improved QOL while patients who received placebo had decreased QOL. These results are similar to those seen in the full study cohort, where differences between epoetin alfa and placebo were significant (P<0.05) for all five primary cancer- and anemia-specific QOL domains evaluated. Although the study was not powered for survival, Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa in both the full study cohort and the hematologic subgroup. Epoetin alfa treatment was well tolerated. Epoetin alfa therapy increased Hb levels, reduced transfusion requirements, and improved QOL in patients with anemia undergoing non-platinum chemotherapy for hematologic malignancies.     

Prevention of anaemia by early intervention with once weekly epoetin alfa during chemotherapy

This study compared the effects of early intervention with standard use of epoetin alfa on haemoglobin (Hb) levels and transfusion requirements in cancer patients receiving chemotherapy. Patients with Hb>10 and < or= 12 g/dL were randomised 1:1 to epoetin alfa (40,000 IU, subcutaneously, once weekly), initiated within 7d of the start of the first on-study chemotherapy cycle (defined as early intervention) versus epoetin alfa when Hb 相似文献   

Early intervention with epoetin beta prevents severe anaemia in lung cancer patients receiving platinum-based chemotherapy: a subgroup analysis of the NeoPrevent study

The NeoPrevent study showed that early intervention with epoetin beta could prevent severe anaemia in patients with solid tumours receiving platinum-based chemotherapy. An early intervention strategy may be particularly warranted in patients with lung cancer, as anaemia is very common in these patients and can be severe. The purpose of this study was to examine the efficacy and safety of epoetin beta in the subpopulation of patients with lung cancer included in the NeoPrevent study. Patients were enrolled if baseline haemoglobin (Hb) levels were 1g/dl) plus the proportion whose Hb was maintained at +/-1g/dl of baseline. Quality of life (QoL) was measured using the linear analogue scale assessment. The NeoPrevent study included 255 patients in total, and the results for the 102 patients with lung cancer (non-small-cell lung cancer 64%; small-cell lung cancer 36%) are presented here. The overall anaemia prevention response was 90%, with Hb response in 60% of patients and maintenance of baseline Hb level in 30%. Only 9% of patients required transfusions. QoL improved significantly in patients with Hb response (p<0.01) and was maintained in non-responders (p>or=0.578). Epoetin beta was effective in preventing severe anaemia in lung cancer patients receiving platinum-based chemotherapy.     

Epoetin alpha prevents anaemia and reduces transfusion requirements in patients undergoing primarily platinum-based chemotherapy for small cell lung cancer.

Anaemia commonly occurs in cancer patients receiving chemotherapy, often necessitating blood transfusion. This multicentre study was designed to evaluate the efficacy and safety of epoetin alpha in preventing the decline in haemoglobin (Hb) level, and to determine whether the transfusion requirement could be reduced, in patients receiving 4-6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer (SCLC). A total of 130 non-anaemic SCLC patients were randomized to receive no additional treatment (n = 44), epoetin alpha 150 IU kg(-1) subcutaneously (s.c.) three times a week (n = 42) or 300 IU kg(-1) s.c. three times a week (n = 44). Reductions in epoetin alpha dosage were made during the study if Hb level increased to >15 g dl(-1). The mean weekly dosage was 335 and 612 IU kg(-1), respectively, in the two active treatment groups. Significantly fewer (P < 0.05) epoetin alpha-treated patients experienced anaemia (Hb < 10 g dl(-1)) during the course of chemotherapy (300 IU kg(-1), 39%; 150 IU kg(-1), 48%; untreated, 66%). This was reflected in the significantly lower number of treated patients transfused [300 IU kg(-1), 20% (P< 0.001); 150 IU kg(-1), 45% (P< 0.05); untreated, 59%]. Epoetin alpha was well-tolerated, and there was no evidence of sustained, clinically significant, hypertension. In summary, epoetin alpha is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC.     

Erythropoietic agents in anaemic patients with cancer: a retrospective observational survey of epoetin alpha, epoetin beta and darbepoetin alpha use in routine clinical practice

This retrospective observational survey assessed, in a routine clinical practice setting, the modalities of treatment with recombinant erythropoietic agents: alpha erythropoietic agents [epoetin alpha (Eprex) and darbepoetin alpha (Aranesp)] and epoetin beta (NeoRecormon). Evolution of haematological response parameters such as haemoglobin (Hb) during treatment of anaemic patients with cancer were contrasted for the different agents. Records of 125 consecutive adult cancer patients (42 epoetin alpha, 40 epoetin beta, 43 darbepoetin alpha) receiving chemotherapy and erythropoietic treatment for anaemia, and treated between September 2003 and February 2004, were analysed. Mean periods of observation of treatment were 103 days (epoetin alpha), 114 days (epoetin beta) and 95 days (darbepoetin alpha). The mean changes in maximum Hb level during treatment were 2.8 g/dl (epoetin alpha), 3.3 g/dl (epoetin beta) and 2.1 g/dl (darbepoetin alpha) (P=0.02, epoetin beta versus darbepoetin alpha). The proportions of patients achieving > or =1 g/ dl Hb increases were 85.7% (epoetin alpha), 87.5% (epoetin beta) and 79.1% (darbepoetin alpha). The mean cumulative doses administered to achieve these increases were 284, 722 IU; 201, 428 IU; and 208, 823 IU [dose calculated (based on equivalent peptide mass) using 1 microg darbepoetin alpha is equivalent to 200 IU epoetin], respectively. The proportions of patients achieving > or =2 g/dl Hb increases were 66.7% (epoetin alpha), 77.5% (epoetin beta) and 58.1% (darbepoetin alpha). This survey suggests that in real-life clinical conditions the available erythropoietic agents increase Hb effectively in anaemic patients with cancer, and that epoetin beta therapy may have therapeutic advantages over the other agents assessed.     

Treatment options for anemia, taking risks into consideration: erythropoiesis-stimulating agents versus transfusions

Erythropoiesis-stimulating agents are indicated for the treatment of chemotherapy induced-anemia in cancer patients. Controlled clinical studies have shown that epoetin alfa consistently and significantly increases levels of hemoglobin (Hb), decreases the need for RBC transfusion, and improves the quality of life that is of such importance in cancer patients with a limited life expectancy. The rise achieved in Hb level correlates with an improvement in quality of life. Studies have also demonstrated that earlier initiation of epoetin therapy (i.e., starting treatment at an Hb level of 10-11 g/dl rather than waiting for Hb to fall to <10 g/dl) is associated with a faster achievement of an optimal Hb level, a lower transfusion requirement, and a maintained quality of life.     

Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy

PURPOSE: To evaluate the safety and efficacy of intravenous (IV) sodium ferric gluconate complex (FG), oral ferrous sulfate, or no iron to increase hemoglobin (Hb) in anemic cancer patients receiving chemotherapy and epoetin alfa. PATIENTS AND METHODS: In this open-label, multicenter trial, 187 patients with chemotherapy-related anemia (Hb <11 g/dl; serum ferritin > or =100 ng/ml or transferrin saturation > or =15%) scheduled to receive chemotherapy and epoetin alfa (40,000 U subcutaneously weekly) were randomized to 8 weeks of 125 mg of IV FG weekly, 325 mg of oral ferrous sulfate three times daily, or no iron. The primary outcome was a change in Hb from baseline to endpoint, first whole-blood or red blood cell transfusion, or study withdrawal. RESULTS: One hundred twenty-nine patients were evaluable for efficacy (FG, n = 41; oral iron, n = 44; no iron, n = 44). Mean increase in Hb was 2.4 g/dl (95% confidence interval [CI], 2.1-2.7) for FG (p = .0092 vs. oral iron; p = .0044 vs. no iron), 1.6 g/dl (95% CI, 1.1-2.1) for oral iron (p =.7695 vs. no iron), and 1.5 g/dl (95% CI, 1.1-1.9) for no iron. Hb response (increase > or =2 g/dl) was 73% for FG (p = .0099 vs. oral iron; p = .0029 vs. no iron), 46% for oral iron (p = .6687 vs. no iron), and 41% for no iron. FG was well tolerated. CONCLUSION: For cancer patients with chemotherapy-related anemia receiving epoetin alfa, FG produces a significantly greater increase in Hb and Hb response compared with oral iron or no iron, supporting more aggressive treatment with IV iron supplementation for these patients.     

Effectiveness of darbepoetin alfa versus epoetin alfa in patients with chemotherapy-induced anemia treated in clinical practice

PRIMARY PURPOSE: The objective of this retrospective observational cohort study was to compare the effectiveness of darbepoetin alfa with that of epoetin alfa in patients with chemotherapy-induced anemia using data from noncontemporaneous chart audits conducted at a community-based oncology practice. MATERIALS AND METHODS: For the first chart audit, data were collected from consecutive patients with nonmyeloid malignancies with diagnoses of chemotherapy-induced anemia and hemoglobin levels < or = 10.5 g/dl who were receiving concurrent chemotherapy and had at least 5 weeks of visits from July-September 2000. After therapeutic substitution of darbepoetin alfa for epoetin alfa for all patients with chemotherapy-induced anemia, data were collected from consecutive darbepoetin alfa-treated patients with diagnoses of chemotherapy-induced anemia and at least 8 weeks of visits from June-October 2002 (darbepoetin alfa was approved in July 2002). RESULTS: Most (86%) of the 212 epoetin alfa-treated patients had received an initial dose of 40,000 U once weekly, and most (85%) of the 196 darbepoetin alfa-treated patients had received a fixed dose of either 100 microg once weekly (49%) or 200 microg every 2 weeks (36%). At 8 weeks, the mean change in hemoglobin level was 1.1 g/dl for the darbepoetin alfa patient group and 1.0 g/dl for the epoetin alfa patient group. DISCUSSION: Utilization, dose escalation rates, and clinical outcomes were considered comparable for the darbepoetin alfa and epoetin alfa patient groups. CONCLUSIONS: Darbepoetin alfa, 100 microg once weekly or 200 microg every 2 weeks, appears to be as effective as epoetin alfa, 40,000 U once weekly, for the treatment of chemotherapy-induced anemia in the clinical practice setting.     

Early Intervention with epoetin alfa during platinum-based chemotherapy: an analysis of quality-of-life results of a multicenter, randomized, controlled trial compared with population normative data

OBJECTIVE: To evaluate the effect of epoetin alfa on quality of life (QOL) in patients with solid tumors and mild-to-moderate anemia receiving platinum-based chemotherapy relative to population norms. METHODS: In the original study, patients (n = 316) with hemoglobin (Hb) levels < or =12.1 g/dl were randomized 2:1 to receive either epoetin alfa at a dose of 10,000 U thrice weekly s.c. or best supportive care (BSC) to compare the effects on transfusion use, hematologic response, and QOL (measured by the Functional Assessment of Cancer Therapy-Anemia [FACT-An]and Cancer Linear Analogue Scale [CLAS]). The QOL data from this previously reported trial were reanalyzed here relative to population norms. RESULTS: Mean baseline QOL scores were similar between groups. At study completion, mean CLAS, FACT-An, FACT-An Anemia subscale, and FACT-An Fatigue subscale scores were significantly higher for patients given epoetin alfa than for those treated with BSC. Compared with population norms, both groups had impaired QOL at baseline. Differences in mean QOL change scores from baseline to study end for epoetin alfa versus BSC were 3.17 points for the FACT-General Total, 9.90 for the FACT-An Fatigue subscale, and 7.30 for the FACT-An Anemia subscale. This was equivalent to corrections in QOL deficits attributable to epoetin alfa of 97.3%, 40.7%, and 38.0% for the FACT-General Total, FACT-An Fatigue, and FACT-An Anemia subscale scores, respectively, versus BSC. A somewhat greater QOL benefit was observed for the FACT-An Fatigue and FACT-An Anemia subscales in the subset of patients with baseline Hb levels >10.5 g/dl. CONCLUSION: Patients in this study had impaired QOL compared with population norms. Early treatment with epoetin alfa to correct anemia improved QOL in a statistically significant and clinically meaningful way, and improvements were greater in patients with baseline Hb levels >10.5 g/dl.     

Low hemoglobin levels: influence on tumor biology and radiotherapy treatment outcome

Anemia promotes intratumoral hypoxia, and in turn, hypoxia may adversely impact treatment outcomes by reducing the effectiveness of radiation therapy and by promoting molecular and cellular changes that favor malignant progression and formation of metastases. Recent experimental and clinical studies have been aimed at further exploring the mechanisms by which anemia and hypoxia exert their negative influence in order to identify the more effective interventions to improve clinical prognosis and outcomes. In a recent study of patients with squamous cell carcinoma of the oral cavity and oropharynx, pretreatment hemoglobin (Hb) level and epoetin alfa therapy were independent prognostic factors for response to radiochemotherapy and locoregional tumor control (P <0.01). Patients with pretreatment Hb levels ⩾14.5 g/dl had significantly (P ⩽0.001–P <0.05) higher complete response, 2-year locoregional control, and 2-year survival rates than patients with Hb levels <14.5 g/dl who had not received epoetin alfa. Further, the response, locoregional control, and survival rates of epoetin alfa–treated patients with a pretreatment Hb <14.5 g/dl were significantly higher than those of patients with pretreatment Hb levels <14.5 g/dl not given epoetin alfa, and were equivalent to those of patients with a pretreatment Hb level ⩾14.5 g/dl. These observations and those of several other studies suggest that stabilization of normal Hb levels and correction of treatment-related anemia may contribute to improved therapeutic outcomes in cancer patients. Controlled prospective clinical trials in larger numbers of cancer patients are clearly warranted.     

Early intervention with epoetin alfa during platinum-based chemotherapy: an analysis of the results of a multicenter, randomized, controlled trial based on initial hemoglobin level

OBJECTIVE: This analysis of the results of a randomized, controlled trial evaluating the effects of epoetin alfa (EPO) therapy on transfusion requirements, hemoglobin (Hb), and quality of life (QOL) in patients with cancer receiving platinum-based chemotherapy was conducted to evaluate the effect of initial Hb level on study outcomes. METHODS: Patients with Hb levels < or =12.1 g/dl were randomized 2:1 to receive EPO, 10,000 U three times weekly s.c. or best supportive care (BSC) until 4 weeks after their last chemotherapy cycle. For this analysis, patients were stratified by baseline Hb level (< or =9.7 g/dl, >9.7 g/dl to < or =10.5 g/dl, >10.5 g/dl to < or =11.3 g/dl, and >11.3 g/dl to < or =12.1 g/dl), and study results were reanalyzed. RESULTS: Significantly fewer EPO patients than BSC patients with initial Hb levels >9.7 g/dl to < or =12.1 g/dl required transfusions. EPO maintained Hb levels throughout the study for patients with Hb levels >11.3 g/dl to < or =12.1 g/dl, compared with a decrease with BSC. For patients with baseline Hb levels >10.5 g/dl, for whom the mean changes from baseline to last assessment were measured by the Cancer Linear Analogue Scale assessments of energy and overall QOL as well as by the Functional Assessment of Cancer Therapy (FACT)-Fatigue and FACT-An Anemia subscale, QOL scores were significantly greater with EPO than with BSC. QOL declined in patients receiving BSC, and the mean decreases in QOL scores were greater for BSC patients with baseline Hb levels >10.5 g/dl, compared with the overall BSC group. CONCLUSION: In patients with cancer receiving platinum-based chemotherapy and with baseline Hb levels >10.5 g/dl, early intervention with EPO reduces transfusions, maintains Hb level, and maintains or improves QOL. This study supports the positive effects of early intervention when analyzed according to initial Hb value.     

Efficacy and safety analysis of epoetin alfa in patients with small-cell lung cancer: a randomized, double-blind, placebo-controlled trial.

PURPOSE: This randomized, double-blind, placebo-controlled trial (N93-004) evaluated the effects of epoetin alfa on tumor response to chemotherapy and survival in patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Adult patients with hemoglobin < or = 14.5 g/dL starting chemotherapy received epoetin alfa 150 U/kg or placebo subcutaneously 3 times weekly until 3 weeks after completion of chemotherapy. Survival was assessed for 3 years. The primary end point was the proportion of patients with complete or partial response after three chemotherapy cycles. RESULTS: The trial was terminated prematurely after 224 of a projected 400 patients were accrued. Baseline characteristics were similar between groups. Epoetin alfa and placebo patients (n = 109 and n = 115, respectively) had mean baseline hemoglobin of 12.8 g/dL and 13.0 g/dL, respectively. Overall tumor response was similar between the epoetin alfa and placebo groups after three chemotherapy cycles (72% and 67%, respectively; 95% CI of difference, -6% to 18%) and after completion of chemotherapy (60% and 56%, respectively; 95% CI of difference, -9% to 17%). Epoetin alfa and placebo groups had similar median overall survival (10.5 and 10.4 months, respectively) and overall mortality (91.7% and 87.8%, respectively; hazard ratio, 1.172; 95% CI, 0.887 to 1.549; P = .264). Hemoglobin was maintained in the prechemotherapy range in epoetin alfa patients, but decreased substantially in placebo patients. Fewer epoetin alfa patients than placebo patients required transfusion. CONCLUSION: These results suggest that in newly diagnosed patients with SCLC epoetin alfa does not affect tumor response to chemotherapy or survival. However, the early trial closure makes these conclusions preliminary.     

Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study.

PURPOSE: To evaluate the effect on survival and quality of life of maintaining hemoglobin (Hb) in the range of 12 to 14 g/dL with epoetin alfa versus placebo in women with metastatic breast cancer (MBC) receiving first-line chemotherapy. PATIENTS AND METHODS: Eligible patients were randomly assigned to receive epoetin alfa 40,000 U once weekly or placebo for 12 months. Study drug was initiated if baseline Hb was < or = 13 g/dL or when Hb decreased to < or = 13g/dL during the study. The primary end point was 12-month overall survival (OS). RESULTS: The study drug administration was stopped early in accordance with a recommendation from the Independent Data Monitoring Committee because of higher mortality in the group treated with epoetin alfa. Enrollment had been completed, with 939 patients enrolled (epoetin alfa, n = 469; placebo, n = 470). Most patients had Hb more than 12 g/dL at baseline (median Hb, 12.8 g/dL) or during the study. From the final analysis, 12-month OS was 70% for epoetin alfa recipients and 76% for placebo recipients (P = .01). Optimal tumor response and time to disease progression were similar between groups. The reason for the difference in mortality between groups could not be determined from additional subsequent analyses involving both study data and chart review. CONCLUSION: In this trial, the use of epoetin alfa to maintain high Hb targets in women with MBC, most of whom did not have anemia at the start of treatment, was associated with decreased survival. Additional research is required to clarify the potential impact of erythropoietic agents on survival when the Hb target range is 10 to 12 g/dL.     

Clinical benefits of epoetin alfa therapy in patients with lung cancer

A retrospective subset analysis of anemic lung cancer patients who participated in three large, multicenter, community-based studies of 3-times-weekly (TIW) or once-weekly (QW) recombinant human erythropoietin (r-HuEPO, epoetin alfa) as an adjunct to chemotherapy was conducted. Patients were treated with epoetin alfa 150 U/kg in the first TIW study and with 10,000 U subcutaneously in the other study, with doubling of the dose if hemoglobin (Hb) response was inadequate. Patients in the QW study received epoetin alfa 40,000 U subcutaneously, which could be increased to 60,000 U. The maximum treatment duration for all three studies was 16 weeks. A total of 1748 lung cancer patients were evaluable for hematopoietic response; 1298 were evaluable for analyses of energy and 1300 were evaluable for analyses of activity and overall quality of life (QOL), as measured by the linear analogue scale assessment (LASA). Within 2 months of therapy, TIW and QW epoetin alfa therapy resulted in significant increases in Hb levels, decreases in transfusion requirements, and improvements in self-reported LASA scores. Increased Hb levels and reduced transfusion rates were demonstrated in the individual studies and in the analysis of data pooled from all three studies. Improvements in QOL parameters were significantly correlated with increased Hb levels. Epoetin alfa was well tolerated in all studies. The clinical benefits and safety profiles of the TIW and the QW schedules appear to be similar. In addition, the QW schedule provides greater convenience to patients and physicians alike. Given the high incidence of anemia and transfusion utilization in patients presenting with lung cancer, epoetin alfa is an effective strategy for correcting anemia in these patients, thereby improving their energy levels, activity levels, and overall QOL.