epoetin-alfa and Carcinoma--Squamous-Cell

This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa).. The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm.. A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms.. This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Carcinoma, Squamous Cell; Chemoradiotherapy; Combined Modality Therapy; Disease-Free Survival; Epoetin Alfa; Erythropoietin; Female; Head and Neck Neoplasms; Hematinics; Hemoglobin A; Humans; Male; Middle Aged; Recombinant Proteins; Squamous Cell Carcinoma of Head and Neck; Time Factors

To evaluate the effect of epoetin alfa on local disease-free survival (DFS), overall survival (OS), and cancer treatment-related anemia and fatigue in patients with head and neck cancer receiving radical radiotherapy with curative intent.. Patients (N = 301) with hemoglobin (Hb) less than 15 g/dL were randomly assigned in a ratio of 1:1 to receive radiotherapy plus epoetin alfa (10,000 U subcutaneously [SC] three times weekly if baseline Hb was < 12.5 g/dL; 4,000 U SC three times weekly if baseline Hb > or = 12.5 g/dL) or radiotherapy alone. Hb levels were monitored weekly. The primary end point was local DFS, defined as the time from random assignment to local disease recurrence or death. Secondary efficacy end points included OS, local tumor response, and local tumor control. Patients were followed at 1, 4, 8, and 12 weeks postradiotherapy and annually for 5 years. Cancer treatment-related anemia and fatigue were evaluated with the Functional Assessment of Cancer Therapy-Anemia and Functional Assessment of Cancer Therapy-Head and Neck. Adverse events were recorded up to 12 weeks postradiotherapy.. Hb levels increased from baseline with epoetin alfa. The median duration of local DFS was not statistically different between groups (observation, 35.42 months; epoetin alfa, 31.47 months; hazard ratio, 1.04; 95% CI, 0.77 to 1.41). Groups did not significantly differ in DFS, OS, tumor outcomes, or cancer treatment-related anemia or fatigue. No new or unexpected adverse events were observed.. Addition of epoetin alfa to radical radiotherapy did not affect survival, tumor outcomes, anemia, or fatigue positively or negatively in patients with head and neck cancer.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Carcinoma, Squamous Cell; Disease Progression; Disease-Free Survival; Epoetin Alfa; Erythropoietin; Fatigue; Female; Head and Neck Neoplasms; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Recombinant Proteins; Survival Rate

This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to 14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC).. Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT.. Both groups were balanced for age, sex, performance status, tumor length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09).. The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.

Topics: Adenocarcinoma; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Epoetin Alfa; Erythropoietin; Esophageal Neoplasms; Female; Fluorouracil; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Radiotherapy Dosage; Recombinant Proteins

According to recent data erythropoietin receptor (EPOR) is expressed not only by bone marrow erythroid progenitors but by endothelial- and cancer cells and it was suggested that erythropoietin (EPO) may affect their functions as well. We have analyzed the effects of recombinant human erythropoietin-alpha (rHuEPOalpha) on radiation sensitivity of EPOR+ human epidermoid carcinoma (A431) xenograft model. In vivo rHuEPOalpha treatment was started after tumor cell inoculation into SCID mice. 5 Gy irradiation was performed on day 14, the effect of which was measured on day 22. Hemoglobin level, tumor-associated microvessels and HIF-1alpha expression of the xenograft were monitored during the experiment. rHuEPOalpha administration prevented the development of tumor-induced anemia of SCID mice and reduced the level of HIF-1alpha expression of the xenograft tumor without affecting tumor growth. We have found that rHuEPOalpha treatment significantly increased the efficacy of antitumor effect of irradiation which was partly mediated by complex effects on tumor-associated microvessels. In vitro rHuEPOalpha did not affect proliferation of A431 cells but enhanced the antiproliferative and proapoptotic effects of irradiation. We concluded that rHuEPOalpha administration positively modulated the antitumoral effects of irradiation at least by two pathways, decreasing systemic hypoxia resulting in decreased tumoral HIF-1alpha expression and enhancing direct effects on tumor-associated microvessels.

Topics: Anemia, Hypochromic; Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Mice, SCID; Microcirculation; Polymerase Chain Reaction; Radiation-Sensitizing Agents; Recombinant Proteins; Transplantation, Heterologous

It has been suggested that hemoglobin levels of 12-14 g/dL are optimal for tumor oxygenation, radiosensitivity, and prognosis. In this prospective study, the authors evaluated the effectiveness of epoetin-alpha to maintain hemoglobin levels at 12-14 g/dL during radiotherapy (RT) for patients with UICC Stage III esophageal carcinoma, and they examined the impact of erythropoetin on overall survival (OS), metastatic-free survival (MFS), and local control (LC).. Sixty patients who received RT between March, 2001 and September, 2004, were included in this prospective, nonrandomized study. Thirty patients received epoetin-alpha (150 IU/kg 3 times per week) during RT (Group A), and 30 patients did not receive epoetin-alpha (Group B). Epoetin-alpha was started at hemoglobin levels < 13 g/dL and was stopped at hemoglobin levels > or = 14 g/dL. Hemoglobin was measured before RT and once weekly during RT.. Both patient groups were balanced for age, gender, performance status, tumor location/length, histology, grading, tumor classification, lymph node status, chemotherapy, treatment (45-50.4 grays [Gy] plus resection vs. 45.0-50.4 Gy vs. 59.4-66.0 Gy), and hemoglobin level before RT. In 20 of 30 patients (67%) from Group A and in 3 of 30 patients (10%) from Group B, > or = 60% of hemoglobin levels during RT were 12-14 g/dL (P = 0.003). The median change in hemoglobin was + 0.4 g/dL per week in Group A and - 0.4 g/dL per week in Group B. LC was significantly better in Group A (66% vs. 38% at 1 year, respectively; P = 0.012), a trend was observed for OS (59% vs. 33%, respectively; P = 0.08), and MFS did not differ significantly (43% vs. 38%, respectively; P = 0.34). No epoetin-alpha-related toxicity was observed.. Epoetin-alpha was effective in maintaining the hemoglobin levels at 12-14 g/dL during RT. The application of epoetin-alpha significantly improved LC, and a trend was observed for OS.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Esophageal Neoplasms; Female; Gamma Rays; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Survival Rate