Hormones in chemotherapy for pancreatic cancer, chemoagents or carriers?
The pancreas, particularly when inflicted with cancer, shelters sex hormones and their receptors more abundantly than some reproductive organs. In the laboratory, the anti-androgen cyproterone inhibits tumour growth while the anti-estrogen tamoxifen exhibits no effect. However, it is thought that the lack of effect from tamoxifen was due to the absence of nuclear estrogen receptors in the laboratory animals, which does not obtain in the human pancreas. Thus at least 4 phase II clinical trials with tamoxifen have been completed for CA pancreas. All but one resulted in at least doubling the average survival. On the other hand, because androgen receptors have only recently been identified in human pancreas, no clinical trial with androgens has been done. Also, quite recently, it has been found that the cytotoxic steroid estramustine binds in the pancreas to a protein with an affinity many times higher than that between the estrogens and their binding protein. However, promising results with tamoxifen from the phase II trials and the rareness of acute side-effects from the anti-estrogen promote the furthering of investigation with the agent. It has also been suggested that tamoxifen, while an anti-cancer agent itself in the pancreas, can simultaneously serve as a target specific carrier for other cytotoxic drugs.
Siu
T O
TO
Tom Baker Cancer Centre, Alberta Cancer Board, Calgary, Canada.
Kwan
W B
WB
D000728:Androgens / Q000627:therapeutic use; D000818:Animals; D004337:Drug Carriers; D004961:Estramustine / Q000627:therapeutic use; D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D005768:Gastrointestinal Hormones / Q000627:therapeutic use; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D013629:Tamoxifen / Q000627:therapeutic use
D000728:Androgens; D004337:Drug Carriers; D004967:Estrogens; D005768:Gastrointestinal Hormones; D006728:Hormones; D013629:Tamoxifen; D004961:Estramustine