Modulation of cytostatic drugs by nifedipine in two heterotransplanted human testicular-cancer cell lines differing in their sensitivity to standard agents

✍ Scribed by Carsen Bokemeyer; Theresa Dunn; Andreas Harstrick; T. Lerch; Hubert Poliwoda; Hans-Joachim Schmoll

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: French
• Weight: 555 KB
• Volume: 56
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910560328

✦ Synopsis

Drug resistance is an important clinical problem in testicular cancer patients with relapsed or refractory disease after firstline chemotherapy. Here we report that the relative reduction in tumour volume in nude mice heterotransplanted with either H 12.1 or H 23.1 human testicular cancer cell lines was significantly increased by addition of the calcium antagonist nifedipine to the maximum tolerated dose (MTD) of cisplatin (DDP). The mean reduction in relative tumour volume at day 30 (rVR) reached statistical significance for both cell lines following combination therapy of DDP with nifedipine compared to DDP alone (55 f 7% versus I 2 f 4% for H 23. I and 60 f 9% vs. 24 f 4% for H 12.1). The synergistic anti-tumour activity of DDP with nifedipine has also been confirmed in H 12. I cells in vitro. However, in vivo, this combination was associated with a concordant increase in therapeutic toxicity. In contrast, no improvement in in vivo anti-tumour activity was obtained by combining similar dose-schedules of nifedipine with the MTD of epirubicin, or with MTDs of vinblastine or etoposide. These results are in agreement with our immunohistochemical finding that H 12.1 and H 23.1 do not over-express the Pgp 170