CA Cancer J Clin 2001; 51:8
doi: 10.3322/canjclin.51.1.8-a
© 2001 American Cancer Society
ANTISENSE DRUG ENHANCES RESPONSE IN CHEMORESISTANT MELANOMAS
| |
Antisense drug and melanoma
|
|
The antisense drug augmerosen improved the effectiveness of chemotherapy and helped shrink tumors in patients with metastatic melanoma, according to a preliminary report in The Lancet (2000;356:1728-1733).
In phase I-II clinical trials, Burkhard Jansen, MD et al of the University of Vienna, treated 14 stage-IV patients with augmerosen—which in earlier animal studies had successfully inhibited production of BCL2 protein—thus sensitizing chemoresistant tumors to chemo-therapy. BCL2 prevents apoptosis and is found in high levels in most melanoma cells.
Jansen gave augmerosen, either by sub-cutaneous injection or intravenously, to all patients in combination with dacarbazine. Most patients had previously failed to respond to the chemotherapy alone.
Six of the 14 patients experienced antitumor activity: One complete response, two partial responses in which tumors shrank to less than half their original size, and three minor responses involving less shrinkage. Also, in another two patients with developing tumors, growth was stopped. The estimated median survival for all patients is now more than one year, which is significantly longer than survival times of four to five months in patients with advanced melanoma after treatment failure of initial systemic therapy.
Another encouraging finding of the study was that augmerosen caused relatively few side effects.
The authors avoided speculation on the relevance of their work to other cancers, focusing only on melanoma. However, antisense drugs are currently being developed for use in other tumors. In an editorial in the Journal of Clinical Oncology (2000;18:1809-1811), antisense expert Alan Gewirtz, MD, of the University of Pennsylvania School of Medicine, wrote that antisense drugs may help scientists find effective nontoxic treatments to block the fundamental processes of the cancer cell.
