Use of irinotecan for treatment of small cell carcinoma of the prostate.
BACKGROUND
Prostatic small cell carcinoma (SCC) is a rare variant of prostate cancer. It is extremely aggressive and resistant to available therapies with a median survival range of 5-17 months. No standard chemotherapeutic regimen has been established for its treatment. In search of a new therapeutic approach, we examined the response of patient-derived prostatic SCC tissue xenografts to irinotecan, a topoisomerase I inhibitor.


METHODS
A tumor tissue line was established from a patient's prostatic SCC by subrenal capsule grafting using NOD-SCID mice. Mice carrying subcutaneous transplants of the tumor line were then treated for 2 weeks with irinotecan alone and in combination with cisplatin. The effect on tumor volume, histopathology, and apoptosis were determined.


RESULTS
The prostatic SCC tissue line resembled the donor tissue in morphologic and immunohistochemical features. Irinotecan (20 mg/kg/day; days 1-3, 8-10) completely arrested xenograft growth with a small reduction in tumor volume and only minor weight loss of the hosts (7%); irinotecan (12 mg/kg; same schedule) + cisplatin (2.5 mg/kg/day; days 1 and 8) had a similar effect, but with lower weight loss. While the growth inhibition involved apoptosis, it was also associated with a marked increase in autophagy.


CONCLUSIONS
Tumor tissue lines established via subrenal capsule xenografting provide models with clinical relevance and the present study suggests that irinotecan could be useful for therapy of refractory prostatic SCC, in particular in combination with cisplatin.
The Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, the University of British Columbia, Vancouver, British Columbia, Canada.
Wei-Lin
WL
Tung
Yuwei
Y
Wang
Peter W
PW
Gout
Dean-Mo
DM
Liu
Martin
M
Gleave
Yuzhuo
Y
Wang
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D004359:Drug Therapy, Combination; D006801:Humans; D000077146:Irinotecan; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013370:Subrenal Capsule Assay
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin