• 10/8/2007
  • Memphis, TN
  • staff
  • CancerConsultants.com

Researchers affiliated with the Danish Head and Neck Cancer Group DAHANCA 10 study have reported that patients with head and neck cancer receiving radiation therapy and prophylactic Aranesp® (darbepoetin alfa) to maintain high hemoglobin levels had a lower disease-free survival than patients receiving placebo. The details of this study were presented at the 14th European Cancer Conference (ECCO) in September, 2007.[1]

Aranesp is an effective agent for increasing hemoglobin levels in patients receiving chemotherapy and decreasing the need for blood transfusions. However, there has been some concern that erythropoiesis-stimulating agents (epoetin alfa and darbepoetin alfa) are associated with increased thromboembolic events and in recurrent malignancies. Recently, researchers affiliated with six randomized controlled trials of Aranesp versus placebo for treatment of chemotherapy induced anemia (CIA) in patients with non-myeloid malignancies have reported that Aranesp decreases transfusion requirements and improves hemoglobin responses without an adverse effect on disease progression or survival.

In most studies of Aranesp, the goal has been to increase the hemoglobin level to 11-13 g/dL to prevent blood transfusions. The purpose of the current study was to determine if allowing more oxygen to squamous cell carcinoma would increase radio sensitivity resulting in better tumor control. Patients in this study had hemoglobin levels maintained between 14 and 15.5 g/dL. In addition, they received the hypoxic radio sensitizer Nimorazole. In total, 522 patients were randomly allocated to receive Aranesp beginning a week before radiotherapy or placebo and 515 were evaluable. More than 91% of Aranesp treated patients achieved the protocol specified hemoglobin levels. The main findings of this study are shown in the following table:

Data are presented for Aranesp first and then the Placebo

Number of Patients 255 260

5 year Loco-regional control 56% 69% (p=0.02)

5 year Disease-Free Survival 48% 69% (p=0.004)

5 year Disease-Specific Survival 51% 67% (p=0.05)

5 year Overall Survival 38% 51% (p=0.08)

These authors also reported that there was no difference in risk of developing distant metastases or in non-cancer related deaths or risk of cardio-vascular events between Aranesp and placebo.

Comments:
This was essentially a negative study showing that increasing hemoglobin values above currently accepted guidelines does not increase but may actually decreases tumor control in patients with head and neck squamous cell carcinoma. The mechanism of this effect is unclear.

Reference:
Overgaard J, Hoff C, Hansen HS, et al. Randomized study of the importance of Novel Erythropoiesis Stimulating Protein (Aranesp®) for the effect of radiotherapy in patients with primary squamous cell carcinoma of the head and neck (HNSCC) – the Danish Head and Neck Cancer Group DAHANCA 10 rand. European Journal of Cancer Supplements. 2007; 5:7, Abstract #6LB.