Is there a possible survival benefit to increasing hemoglobin levels with epoetin alfa during chemotherapy?

• Published in: European journal of cancer supplements Vol. 2; no. 2; pp. 20 - 28
• Main Authors: Aapro, M, Bajetta, E, Freund, M, Littlewood, T.J, Nortier, J.W.R, Rapoport, B
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 01.02.2004; Elsevier
• Subjects: Anemia; Biological and medical sciences; Chemotherapy; Epoetin alfa; Medical sciences; Pharmacology. Drug treatments; Quality of life; Tumor hypoxia; Tumors; Tumor hypoxia; Chemotherapy; Epoetin alfa; Anemia; Quality of life; Antineoplastic agent; Cancerology; Treatment; Hemoglobin; Pharmacology; Survival
• ISSN: 1359-6349; 1878-1217
• DOI: 10.1016/S1359-6349(03)00104-6

Anemia is common in cancer patients during chemotherapy. The study discussed in this article was primarily designed to assess the effects of epoetin alfa on transfusion requirements, hematopoietic response, quality of life (QOL), and safety in cancer patients receiving nonplatinum–based chemotherapy under randomized, double-blind, placebo-controlled conditions. Over the course of the study, a growing body of evidence from other studies suggested an association between low hemoglobin (Hb) levels and poorer prognosis in patients receiving radiotherapy, chemotherapy or combination therapies. Therefore, prior to unblinding, the study protocol was amended to explore a possible relationship between increased Hb levels and survival by collecting survival data for 12 months after the last patient completed the study. A total of 375 patients with solid tumors or nonmyeloid hematologic malignancies (Hb ⩽10.5 g/dl or Hb >10.5 g/dl but ⩽12.0 g/dl with a decrease of ⩾1.5 g/dl per cycle or month since starting chemotherapy) were randomized 2:1 to receive 150–300 IU/kg epoetin alfa ( n=251) or placebo ( n=124) subcutaneously three times weekly for 12–24 weeks, or for 3–6 chemotherapy cycles plus 4 weeks after chemotherapy. The primary efficacy endpoint was the proportion of patients transfused. Secondary endpoints included changes in Hb level and QOL measurements. Hematopoietic response in terms of the proportion of responders (patients whose Hb level increased by at least 2 g/dl during the study without transfusion) and correctors (patients who achieved an Hb level of at least 12 g/dl during the study without transfusion) were also determined. Compared with placebo, epoetin alfa significantly decreased transfusion requirements ( P=0.0057) and increased Hb levels ( P <0.001). There were significantly more responders and correctors in the epoetin alfa group than in the placebo group ( P <0.001 for both). Epoetin alfa also provided significantly greater improvements ( P <0.01) in all primary cancer- and anemia-specific QOL domains, including energy level, ability to do daily activities, fatigue and overall QOL score. Adverse events were comparable between treatment groups. Median survival times were 17 months for epoetin alfa–treated patients and 11 months for placebo-treated patients. Kaplan-Meier 12-month survival estimates were 60% for epoetin alfa-treated patients and 49% for placebo-treated patients. The log-rank test indicated a trend in overall survival for epoetin alfa ( P=0.13). These survival results must be interpreted with caution because the study was not powered to assess survival, nor was it controlled for stage of disease, bone marrow involvement, intensity of chemotherapy or disease progression. This study allowed regulatory approval of epoetin alfa for treatment of non-cisplatin–induced chemotherapy-related anemia. Epoetin alfa also decreases the impact of anemia on QOL, and may improve survival of cancer patients.