Background: MEN4901/T-0128 is a camptothecin conjugate in which 7-ethyl-10-aminopropyloxy- camptothecin (T-2513) is bound to a biodegradable carboxymethyldextran via a Gly-Gly-Gly linker. Previous experiments showed that MEN4901/T-0128 is more efficacious than Irinotecan and is an excellent candidate for the treatment of solid tumors. The aim of the study was to investigate the therapeutic potential of MEN4901/T-0128 in two experimental metastatic models of human carcinoma. Methods: MEN4901/T-0128 and irinotecan activity was assessed in early and advanced metastasis models of human colon carcinoma developed by surgical orthotopic implantation (SOI) of green fluorescent protein-expressing HT-29 cells in nude mice. MEN4901/T-0128 and irinotecan were given intravenously at various doses and schedules (Model 1). The IGROV-1 liver metastatic model was obtained by tumor cell injection into the spleen of nude mice. MEN 4901/T-0128 was given iv at 160 mg/kg (expressed as T-2513 equivalent, single dose) and irinotecan at 60 mg/kg (q4dx4) (Model 2). Results: In the HT-29 model, treatment started on day 49 after SOI, 19 out of the 20 untreated controls had lymph node metastasis at sacrifice on day 71 after SOI. MEN4901/T-0128, when treatment started on day 49, was effective on the primary tumor growth and metastasis to mesentery lymph nodes (Table). In the IGROV-1 model, animals receiving MEN4901/T-0128 didn’t develop liver tumor foci since and no increase in liver weight was observed up to 82 days after tumor inoculation. On the contrary, Irinotecan treated mice showed a 3-fold increase in liver weight. Moreover, mice developed ascites at 24+2 days, 33+4 days and >82 days in control, irinotecan and MEN4901/T-0128 treated animals, respectively. Thus, MEN4901/T-0128 exerted remarkable survival time of treated mice. Conclusions: These data underlined the potential for clinical antitumor and antimetastatic efficacy of MEN4901/T-0128.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]
American Association for Cancer Research