Phase III trial to evaluate the efficacy of maintaining hemoglobin levels above 12.0 g/dL with erythropoietin vs above 10.0 g/dL without erythropoietin in anemic patients receiving concurrent radiation and cisplatin for cervical cancer

Gynecol Oncol. 2008 Feb;108(2):317-25. doi: 10.1016/j.ygyno.2007.10.011. Epub 2007 Nov 26.

Abstract

Purpose: To determine whether maintaining HGB levels > or = 12.0 g/dL with recombinant human erythropoietin (R-HUEPO) compared to "standard" treatment (transfusion for HGB < or = 10.0 g/dL) improves progression-free survival (PFS), overall survival (OS) and local control (LC) in women receiving concurrent weekly cisplatin and radiation (CT/RT) for carcinoma of the cervix. In addition, to determine whether platinum-DNA adducts were associated with clinical characteristics or outcome.

Methods: Patients with stage IIB-IVA cervical cancer and HGB < 14.0 g/dL were randomly assigned to CT/RT+/-R-HUEPO (40,000 units s.c. weekly). R-HUEPO was stopped if HGB > 14.0 g/dL. Endpoints were PFS, OS and LC. Platinum-DNA adducts were quantified using immunocytochemistry assay in buccal cells.

Results: Between 08/01 and 09/03, 109 of 114 patients accrued were eligible. Fifty-two received CT/RT and 57 CT/RT+R-HUEPO. The study closed prematurely, with less than 25% of the planned accrual, due to potential concerns for thromboembolic event (TE) with R-HUEPO. Median follow-up was 37 months (range 9.8-50.4 months). PFS and OS at 3 years should be 65% and 75% for CT/RT and 58% and 61% for CT/RT+R-HUEPO, respectively. TE occurred in 4/52 receiving CT/RT and 11/57 with CT/RT+R-HUEPO, not all considered treatment related. No deaths occurred from TE. High-platinum adducts were associated with inferior PFS and LC.

Conclusion: TE is common in cervical cancer patients receiving CT/RT. Difference in TE rate between the two treatments was not statistically significant. The impact of maintaining HGB level > 12.0 g/dL on PFS, OS and LC remains undetermined.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anemia / blood
  • Anemia / drug therapy*
  • Antineoplastic Agents / therapeutic use*
  • Cisplatin / therapeutic use*
  • Combined Modality Therapy
  • DNA Adducts
  • Erythropoietin / adverse effects
  • Erythropoietin / therapeutic use*
  • Female
  • Hemoglobins / metabolism*
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Recombinant Proteins
  • Thromboembolism / chemically induced
  • Uterine Cervical Neoplasms / blood*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy*

Substances

  • Antineoplastic Agents
  • DNA Adducts
  • Hemoglobins
  • Recombinant Proteins
  • Erythropoietin
  • Cisplatin