Beyond The Abstract A Phase II Clinical Trial Of Sorafenib In Androgen Independent Prostate Cancer
This is a two stage study, and results from stage one have been published. The primary objective of this study was to determine if sorafenib is associated with a 50%, 4 month probability of progression free survival (PFS). Disease progression was determined by clinical, radiographic and PSA criteria. No complete or partial response was observed and of note 17 out of 22 patients progressed by PSA criteria. Six of these patients had a fall in PSA immediately after discontinuation of sorafenib and importantly two patients demonstrated improvement of metastatic lesions on bone scan despite rise in PSA and one patient reported significant decrease in narcotic requirements for pain management.
These clinical observations were in concordance with in-vitro findings where repeated treatment with sorafenib resulted in increased PSA secretion for sorafenib concentrations of 2.5-10 µM, with simultaneous cell growth inhibition. The exact mechanism of increase in PSA secretion is not known, but this observation suggests that PSA may not be a good marker to measure the sorafenib activity. Several other agents like TNP-470, sodium phenylacetate and phenylbutyrate have shown similar results both in in-vitro and clinical studies4.
Sorafenib was well tolerated and a subset of patients appears to benefit from sorafenib treatment. Following the observations that PSA is not a suitable marker of sorafenib activity, for second stage the disease progression criteria was modified to not include the PSA. Twenty-four patients have been accrued in second stage and further investigation using only clinical and radiographic endpoints in ongoing. Data from stage two will be analyzed after completion of the study.
References
1. Weidner, N., et al., Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol, 1993. 143(2): p. 401-9.
2. Erlich, S., et al., Ras inhibition results in growth arrest and death of androgen-dependent and androgen-independent prostate cancer cells. Biochem Pharmacol, 2006. 72(4): p. 427-36.
3. Bakin, R.E., et al., Attenuation of Ras signaling restores androgen sensitivity to hormone-refractory C4-2 prostate cancer cells. Cancer Res, 2003. 63(8): p. 1975-80.
4. Dixon, S.C., K.B. Knopf, and W.D. Figg, The control of prostate-specific antigen expression and gene regulation by pharmacological agents. Pharmacol Rev, 2001. 53(1): p. 73-91.
Written by
Lokesh Jain, MD, and William Figg, MD, as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
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Dincolo de abstract Un studiu clinic de fazã II a sorafenibului Androgen independent în cancerul de prostatã - Beyond The Abstract A Phase II Clinical Trial Of Sorafenib In Androgen Independent Prostate Cancer - articole medicale engleza - startsanatate