Annals of Oncology Advance Access originally published online on October 18, 2005
Annals of Oncology 2006 17(3):531-533; doi:10.1093/annonc/mdj028
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2005 European Society for Medical Oncology
letter to the editor |
Bevacizumab plus high-dose ifosfamide, etoposide and carboplatin (HD-ICE) as third-line salvage chemotherapy induced an unexpected dramatic response in highly platinum refractory germ-cell cancer
Primary resistance of germ-cell cancer to cisplatinum-based chemotherapy is associated with poor therapeutic outcome. Salvage chemotherapy consists of combinations including cisplatin, carboplatin, oxaliplatin, ifosfamide, etoposide, paclitaxel or gemcitabine at standard doses [1
]. The role of high-dose chemotherapy in patients truly refractory to standard dose platinum-based combinations is still a matter of debate. Vaena et al. [2] recently reported a better outcome of patients after one or two cycles of salvage high-dose chemotherapy as could be expected from the ‘Bayer score’. In contrast, in a recent randomised trial of the European Group for Blood and Marrow Transplantation (EBMT) comparing standard conventional salvage to high-dose intensification chemotherapy, the addition of high-dose chemotherapy could not improve survival [3].
Vascular endothelial growth factor (VEGF) is overexpressed and represents an independent risk factor in germ-cell cancer [4]. Thus, targeting VEGF by the monoclonal humanized antibody bevacizumab might be a promising treatment approach for patients with highly vascularized tumors like choriocarcinoma, particularly since bevacizumab augments significantly the activity of conventional chemotherapy in other types of cancer such as colorectal cancer or non-small-cell lung cancer [5, 6].
At our institution we treated, to our knowledge for the first time, a young man with poor prognosis germ-cell cancer [choriocarcinoma and embryonal carcinoma; serum ß-human chorionic gonadotropin (HCG) 80506 U/l, serum 
-fetoprotein (AFP) 100.9 ng/ml], continuously refractory to three lines of standard chemotherapy with a combination regime of high-dose ifosfamide 2000 mg/m2 days 1–6, etoposide 200 mg/m2 days 1–6 and carboplatin 200 mg/m2 days 1–6 (ICE) in combination with bevacizumab 7.5 mg/kg body weight day 1, repeated on day 22. Autologous stem cells were reinfused on day 8. Beside grade 4 hematotoxicity we observed no further toxicity higher than grade 2 (common toxicity criteria), in particular no unanticipated toxicity due to bevacizumab. At the end of the first chemotherapy cycle we observed a dramatic response with a ß-HCG decline close to normal (Figure 1A) and partial remission of liver metastasis by ultrasound examination (not shown). The second to fourth cycle of this individual treatment approach was applied with 25% dose reduction and led to a further decrease of ß-HCG and the former liver metastasis nearly completely diminished in CT scans (Figure 1B, C). Overall, the patient achieved a good marker (>99%) and radiological partial response close to complete response. Progression-free survival was 5 months and the patient died 4 months later with rapidly progressive disease.
|
The role of high-dose chemotherapy as salvage chemotherapy in platinum refractory patients is still a matter of debate. Based on reports from the literature and our own long-term experience, no tremendous response to high-dose chemotherapy could be anticipated in patients truly refractory to cisplatinum and continuously refractory to three lines of conventional chemotherapy [3
, 7]. Although the progression-free survival was rather short lived, the observed dramatic response to third-line salvage therapy itself was unexpected. Thus, it is tempting to speculate that bevacizumab might potentiate the activity of high-dose chemotherapy in germ-cell cancer leading to the dramatic response observed in this patient. In conclusion, the combination of bevacizumab plus HD-ICE and autologous stem cell transplantation is feasible and induced an unexpected dramatic response in a patient with highly chemotherapy refractory germ-cell cancer. This observation might provide the basis for further evaluation of bevacizumab plus HD-ICE as a potential salvage protocol for the treatment of patients with highly refractory germ-cell cancer.
Department of Hematology/Oncology, Martin-Luther University Halle-Wittenberg, 06120 Halle/Saale, Germany
* (E-mail: wieland.voigt{at}medizin.uni-halle.de)
References
1. Schmoll HJ, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377–1399.
2. Vaena DA, Abonour R, Einhorn LH. Long-term survival after high-dose salvage chemotherapy for germ cell malignancies with adverse prognostic variables. J Clin Oncol 2003; 21: 4100–4104.
3. Pico JL, Rosti G, Kramar A et al. A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours. Ann Oncol 2005; 16: 1152–1159.
4. Fukuda S, Shirahama T, Imazono Y et al. Expression of vascular endothelial growth factor in patients with testicular germ cell tumors as an indicator of metastatic disease. Cancer 1999; 85: 1323–1330.[CrossRef][Web of Science][Medline]
5. Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335–2342.
6. Johnson DH, Fehrenbacher L, Novotny WF et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 2004; 22: 2184–2191.
7. Beyer J, Kramar A, Mandanas R et al. High-dose chemotherapy as salvage treatment in germ cell tumors: a multivariate analysis of prognostic variables. J Clin Oncol 1996; 14: 2638–2645.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||