Treatment-induced anaemia and its potential clinical impact in patients receiving sequential high dose chemotherapy for metastatic testicular cancer

Abstract

First-line sequential high dose chemotherapy is under investigation in patients with "poor prognosis" metastatic germ cell tumours in order to improve survival. Despite the use of autologous peripheral blood stem cell transplantation and granulocyte colony stimulating factor chemotherapy dose intensification is associated with severe haematotoxicity including anaemia, which may significantly affect quality of life and tolerability of chemotherapy. This study investigates the frequency and degree of anaemia in patients receiving first-line sequential high dose chemotherapy for metastatic testicular cancer and the impact of anaemia on treatment outcome. A total of 101 newly diagnosed patients with "poor prognosis" metastatic nonseminomatous germ cell tumours were treated with one cycle of standard VIP followed by three cycles of HD-VIP-chemotherapy (etoposide, ifosfamide, cisplatin) within a large phase I/II study. Differential blood cell counts were taken prior, during and after every cycle of chemotherapy. Additionally, the numbers of red blood cell and platelet transfusions were recorded. Kaplan-Meier analyses were performed to correlate pre-treatment and post-treatment haemoglobin values to response and overall survival. Forty-eight per cent of the patients were classified anaemic (haemoglobin <12 g dl(-1)) prior to the start of chemotherapy. The application of sequential HD-VIP resulted in median haemoglobin nadirs between 7.8 g dl(-1) (range 5.5-11.1 g dl(-1)) in the first cycle and 7.6 g dl(-1) (range 6.0-11.4 g dl(-1)) in the third cycle despite the frequent use of red blood cell transfusions. Almost all patients (99%) had haemoglobin levels <10 g dl(-1) at some timepoint during first-line sequential high dose chemotherapy. Overall, 97 patients received red blood cell transfusions with a median of 10 units (range 2-25) per patient during the four consecutive cycles of therapy. The time to first transfusion was shortest in patients with the lowest initial haemoglobin values. While there was no prediction of response or outcome by baseline haemoglobin-levels, a significant survival difference in favour of patients with a haemoglobin value >10.5 g dl(-1) after completion of four cycles of therapy (at leukocyte recovery after the last cycle) compared to those with haemoglobin values <10.5 g dl(-1) was found with 3-year overall survival rates of 87% vs 68%, respectively (P<0.05). Severe anaemia is a very frequent side effect of sequential dose intensive therapy in patients with germ cell cancer, with almost all patients becoming transfusion dependent. Despite the frequent use of red blood cell transfusions, median haemoglobin nadirs remained about 7.5-8 g dl(-1) during therapy. A correlation of haemoglobin-values after completion of therapy to overall treatment outcome was found.

Figure 1

Overall survival time of patients with Hb values > or <10.5 g dl⁻¹ calculated since completion of the HD-VIP-chemotherapy.