Impact of hemoglobin level and use of recombinant erythropoietin on efficacy of preoperative chemoradiation therapy for squamous cell carcinoma of the oral cavity and oropharynx

Int J Radiat Oncol Biol Phys. 2001 Jul 1;50(3):705-15. doi: 10.1016/s0360-3016(01)01488-2.

Abstract

Purpose: We assessed the influence of hemoglobin level and r-HuEPO administration on response to chemoradiotherapy, locoregional tumor control, and overall survival in patients treated with neoadjuvant chemoradiotherapy and surgery for a squamous cell carcinoma of the oral cavity or oropharynx.

Methods and materials: The 191 study patients were treated with mitomycin C (15 mg/m(2) day 1), 5-fluorouracil (750 mg/m(2)/day, days 1-5), and radiotherapy (50 Gy in 25 fractions weeks 1-5), followed by resection of the primary tumor bed and neck dissection at the General Hospital Vienna, Austria, between November 1989 and October 1998 for a T2-4, N0-3, M0 SCC of the oral cavity or oropharynx. Starting in May 1996, patients with a low hemoglobin (Hgb) before or during chemoradiotherapy received r-HuEPO 10,000 IU/kg s.c. 3-6 times/week until the week of surgery.

Results: On multivariate analysis, Hgb level and use of r-HuEPO were independent prognostic factors for response to chemoradiotherapy and locoregional tumor control (p < 0.01). Pathologic response to neoadjuvant therapy was also predictive of locoregional control (p < 0.001). Patients with a pretreatment Hgb > or = 14.5 g/dL had significantly higher complete response, locoregional control, and survival rates than the patients with a pretreatment Hgb < 14.5 g/dL who did not receive r-HuEPO (p < 0.05). The response, control, and survival rates in patients with a pretreatment Hgb < 14.5 g/dL given r-HuEPO were significantly higher than in low Hgb patients not given r-HuEPO (p < or = 0.001) and equivalent to patients with a pretreatment Hgb > 14.5 g/dL (p > or = 0.3).

Conclusion: Low pretreatment Hgb is a negative prognostic factor for oral cavity and oropharyngeal SCCA patients, but was completely abrogated by r-HuEpo administration during neoadjuvant chemoradiotherapy. Randomized trials of radiation and/or chemotherapy with or without r-HuEPO for patients whose Hgb level is either low at the start of therapy or is anticipated to become low during therapy are indicated.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Squamous Cell / blood*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Erythropoietin / adverse effects
  • Erythropoietin / therapeutic use*
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Hemoglobins / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Mitomycin / administration & dosage
  • Mitomycin / adverse effects
  • Mouth Neoplasms / blood*
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / therapy*
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Oropharyngeal Neoplasms / blood*
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / therapy*
  • Preoperative Care
  • Recombinant Proteins
  • Retrospective Studies

Substances

  • Hemoglobins
  • Recombinant Proteins
  • Erythropoietin
  • Mitomycin
  • Fluorouracil