Efficient carboplatin single therapy in a mouse model of human testicular nonseminomatous germ cell tumor.
OBJECTIVE
Cisplatin based combination therapy has shown excellent clinical results in patients with testicular nonseminomatous germ cell tumor but chemotherapy induced morbidity and reduced patient compliance are limiting factors in this regimen. To decrease cisplatin based combination therapy induced morbidity we examined carboplatin versus etoposide single therapy in an animal model.


METHODS
A total of 180 SCID mice bearing testicular nonseminomatous germ cell tumor xenografts received 120 mg./kg. carboplatin as a single cycle, 60 or 30 mg./kg. carboplatin cycled twice, 80, 50 or 30 mg./kg. etoposide cycled twice, or Ringer solution as the control. An additional 20 sham treated and 20 untreated mice also served as controls. Histological and immunocytochemical testing, in vivo microscopy, vascular corrosion casting, serum tumor markers, complete blood count and real-time polymerase chain reaction were used to monitor therapy efficacy.


RESULTS
Carboplatin at 60 mg./kg. cycled twice eradicated the tumor and significantly reduced vascular density and vascular endothelial growth factor-A messenger RNA (p <0.05). Elevated tumor markers returned to baseline after carboplatin administration. Therapy was well tolerated, resulting thrombocytopenia disappeared 6 weeks after therapy and the animals were tumor-free 6 months after treatment. Although 120 mg./kg. carboplatin eradicated the tumor, it resulted in extensive mortality and morbidity. Single treatment 30, 50 and 80 mg./kg. etoposide failed.


CONCLUSIONS
Carboplatin single therapy was highly effective in our nonseminomatous germ cell tumor model and it may be examined in future clinical trials in patients with high risk stage I nonseminomatous germ cell cancer for reducing cisplatin based combination therapy induced morbidity. Vascular density and vascular endothelial growth factor messenger RNA were elevated in our animal model and deserve further study in nonseminomatous germ cell tumor cases as potential risk factors.
Aharinejad
Seyedhossein
S
Laboratory for Cardiovascular Research, Department of Anatomy, Center for Biomedical Research, University of Vienna, Waehringerstrasse 13, Vienna A-1090, Austria.
Fink
Melanie
M
Abri
Hojatollah
H
Nedwed
Stephan
S
Schlag
Michael G
MG
Macfelda
Karin
K
Abraham
Dietmar
D
Miksovsky
Aurelia
A
Höltl
Eva
E
Höltl
Wolfgang
W
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D001772:Blood Cell Count; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use; D018237:Germinoma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008855:Microscopy, Electron, Scanning; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D005047:Etoposide; D016190:Carboplatin