Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: Preliminary results of a randomized, open-labeled, phase II trial

Self Cite

Summary The purpose of this study was to determine the safety, efficacy and impact on quality of life of recombinant human erythropoietin (r-HuEPO) for cancer patients undergoing radiotherapy (RT). An open-labelled randomized design was used, with patients randomized to either treatment or control arms. Patients in the treatment arm received r-HuEPO given by subcutaneous injection at a dose of 200 units kg-' day-' plus oral iron supplements (ferrous sulphate 325 mg p.o. t.i.d.). Entry was restricted to patients with carcinoma of the lung, uterine cervix, prostate or breast who presented for RT with anaemia parameters reflective of 'the anaemia of chronic disease'. Radiotherapy policies (portals, doses, fraction size, etc.) were determined by the site and stage of disease. Complete blood counts (CBCs) were obtained weekly. The target level of haemoglobin was 15 g dl-1 for men and 14 g dl-1 for women. Quality of life (QOL) was assessed weekly by using an analogue scale to judge energy, activities of daily living and overall quality of life. Forty-eight patients were entered in the study, 24 in the treatment arm and 24 in the control arm. The prerandomization demographic characteristics and mean laboratory values were comparable in both arms. The mean haemoglobin at completion was 13.6 g dl-1 for r-HuEPO-treated patients compared with 11.0 g dl-1 for control subjects (P= 0.0012). Patients who received r-HuEPO demonstrated a mean weekly haemoglobin increase of 0.41 g dl-1 compared with a decrease in mean haemoglobin level in controls for 6 of the 7 weeks of the study (mean weekly decrease of 0.073 g dl-'). Target levels of haemoglobin were achieved by 41.6% of r-HuEPO-treated patients compared with none of the control subjects. The mean platelet count declined in both arms of the study with RT but the decline from pretreatment was less rapid in r-HuEPO-treated patients (11.2% decrease) compared with controls (26.3% decrease) and was statistically significant during weeks 4-6. Toxicity was minor with only mild irritation at the injection site. Mean quality of life end points were superior in the treatment arm but not statistically significant. r-HuEPO had a beneficial effect on weekly haemoglobin levels in patients undergoing RT with response rates similar to other studies. There was also a less rapid decline in weekly platelet counts in r-HuEPO-treated patients compared with control subjects. Further studies are needed to address the optimum dose and scheduling as well as the impact of r-HuEPO on clinical outcomes.

Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Effect of subcutaneous recombinant human erythropoetin in cancer patients receiving radiotherapy: final report of a randomized, open-labelled, phase II trial

Sweeney

Nicolae²,

Ignacio³

et al. 1998

Self Cite

“…However, many of the published QoL studies in anaemic cancer patients have tended to employ generic and non-specific scales such as the WHO Performance Status Indicator (Ludwig et al, 1993;Mittelman et al, 1997) and the Linear Analogue Scale Assessment (LASA, also known as CLAS, Cancer Linear Analogue Scale) (Abels, 1992(Abels, , 1993Case et al, 1993;Vijayakumar et al, 1993;Glaspy et al, 1997).…”

mentioning

confidence: 99%

The level of haemoglobin in anaemic cancer patients correlates positively with quality of life

Lind

Vernon

Cruickshank³

et al. 2002

105

The aim of this study was to assess the relationship between haemoglobin level and quality-of-life in anaemic cancer patients. Patients, diagnosed with one of four cancers, were recruited if their haemoglobin level was <12 g dl −1 (female) or <13 g dl −1 (male). The condition-specific Functional Assessment of Cancer Therapy – Anaemia and the generic SF-36 were used to assess quality-of-life. Thirty-six per cent of the 179 recruited patients had breast cancer, 28% ovarian cancer, 25% lung cancer, and 11% multiple myeloma. Their mean (s.d.) haemoglobin level was 10.66 (1.04) g dl −1 . Partial correlations controlling for the potentially confounding effects of age, gender, and time since diagnosis found significant positive relationships between haemoglobin and all domains of the Functional Assessment of Cancer Therapy – Anaemia, and with all but two of the SF-36 domains. On linear regression controlling for the same factors, each unit haemoglobin rise equalled an average 8.19 Functional Assessment of Cancer Therapy – Anaemia, and an average 6.88 Functional Assessment of Cancer Therapy–Fatigue, increase. Haemoglobin accounted for a similar amount of variability (8%) in SF-36 scores. In conclusion, quality-of-life has been found to be significantly positively related to haemoglobin level in anaemic cancer patients. This suggests that normalisation of haemoglobin in cancer patients is likely to increase their quality-of-life. The greater sensitivity of the condition-specific Functional Assessment of Cancer Therapy – Anaemia compared with the generic SF-36 suggests that the Functional Assessment of Cancer Therapy – Anaemia can be used alone to assess quality-of life in this patient group. British Journal of Cancer (2002) 86 , 1243–1249. DOI: 10.1038/sj/bjc/6600247 www.bjcancer.com © 2002 Cancer Research UK

“…Most studies of the effect of rhEPO on the anaemic state during radiotherapy have generally only focused on changes in RBCrelated parameters (Lavey et al, 1993;Vijayakumar et al, 1993) and did not examine changes in radiosensitivity. Only Joiner et al (1993) used rhEPO to correct a tumour-associated anaemia and measured radiosensitivity in anaemic animals as well as in mice in which anaemia was treated with different doses of rhEPO.…”

mentioning

confidence: 99%

Enhanced radiosensitivity in experimental tumours following erythropoietin treatment of chemotherapy-induced anaemia

Thews

Koenig²,

Dk³

et al. 1998

130

Summary The radiosensitivity of solid tumours in anaemic rats treated with recombinant human erythropoietin (rhEPO, epoetin beta) was studied. Anaemia was induced by a single dose of carboplatin (45 mg kg-' i.v.), resulting in a reduction in the haemoglobin concentration by 30%. In a second group, the development of anaemia was prevented by rhEPO (1000 IU kg-1) administered s.c. three times per week starting 6 days before the carboplatin application. Three days after carboplatin treatment, DS-sarcomas were implanted subcutaneously onto the hind foot dorsum. Neither carboplatin nor rhEPO treatment influenced tumour growth rate. Five days after implantation, tumours were irradiated with a single non-curative dose (10 Gy), resulting in a growth delay with a subsequent regrowth of the tumours. In the rhEPO-treated group, the growth delay lasted significantly longer (9.5 days vs. 4.5 days) and the regrowth was slower (6.0 days vs. 4.1 days) compared with the anaemic group. These data suggest that the correction of chemotherapy-induced anaemia by rhEPO (epoetin beta) treatment increases tumour radiosensitivity, presumably as a result of an improved oxygen supply to tumour tissue.