Low dose carboplatin combined with angiostatic agents prevents metastasis in human testicular germ cell tumor xenografts.

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: J Urol. 2003 Oct;170(4 Pt 1):1388-93

Abraham D, Abri S, Hofmann M, Höltl W, Aharinejad S.
Department of Anatomy, University of Vienna, Austria.
Low dose chemotherapy combined with angiogenesis inhibitors has been
shown to be more effective for experimental tumor treatment than
chemotherapy alone. To our knowledge whether germ cell tumors could
benefit from this treatment strategy remains to be evaluated. We
examined the efficacy of angiostatic thrombospondin-1 (TSP-1),
endostatin and combined angiostatic/low dose carboplatin in mice
xenografted with human nonseminomatous germ cell tumor.
We monitored tumor progression and angiogenesis in the
established model of human nonseminomatous germ cell tumor xenograft in
120 SCID mice using intravital video microscopy, immunocytochemistry
and real-time polymerase chain reaction. Mice received TSP-1 (20 mg/kg
daily) or endostatin (10 mg/kg daily) subcutaneously (via osmotic mini
pumps) for 2 weeks starting 15 days after cancer cell grafting,
carboplatin cycled twice (30 mg/kg intraperitoneally days 14 and 21
after cancer cell grafting), or a combination of carboplatin with TSP-1
or endostatin. Untreated, sham and tumor bearing mice treated with
Ringer's solution served as controls.
RESULTS: Primary tumor
development was not affected in mice treated with TSP-1, endostatin or
carboplatin alone. All animals had metastases at 6 months, while
metastasis did not develop following the combination of carboplatin
with TSP-1 or endostatin. This combined therapy suppressed tumor
angiogenesis, enhanced apoptosis in tumor cells and decreased vascular
endothelial growth factor-A tissue mRNA expression vs controls (p
CONCLUSIONS: These data indicate that angiostatic agents
added to low dose carboplatin have the ability to suppress the
progression of human germ cell tumor xenografts toward a metastatic
phenotype. Therefore, this treatment strategy might be beneficial to
prevent metastasis in germ cell tumors.