PDGFR inhibition accelerates disease progression in men with mCRPC

A while back now the research group at M. D. Anderson Cancer Center initiated a Phase II clinical trial of a drug called tandutinib in the treatment of men with metastatic, castration-resistant prostate cancer (mCRPC) who had already had taxane-based chemotherapy.

The clinical trial protocol is available on the ClinicalTrials.gov web site. What Mathews and his colleagues were trying to find out was whether tandutinib — which is a potent inhibitor of platelet-derived growth factor receptor (PDGFR) — might have a beneficial effect in the management of late stage prostate cancer. They knew before they began that PDGFR is commonly expressed  in bone metastases of patients with mCRPC.

The patients all received a daily, oral dose of 500 mg of tandutinib.

Here are the core results of the trial:

  • 18 patients were enrolled of an originally planned 30 patients.
  • The average (median) age of the patients enrolled was 66 years (range, 47-81 years).
  • 15/18 patients were evaluable for efficacy.
  • 5/6 evaluable tumors were PDGFR positive.
  • The average (mean) level of urine N-telopeptide declined from 123.7 nmol/mmol Cr (at baseline) to 41.0 nmol/mmol Cr (at Cycle 2 Day 1).
  • A decrease in the peripheral blood leukocyte level of PDGFR to < 0.5 as compared to > 0.5 was associated with a progression-free survival of 6 weeks versus 8 weeks.
  • Similarly, a decrease in the peripheral blood leukocyte level of PDGFR to < 0.5 as compared to > 0.5 was associated with an overall survival of 26.6 weeks versus 42.9 weeks.

In other words, the effective inhibition of PDGFR with tandutinib correlated with accelerated disease progression. Mathew et al. note that their finding suggests an association between expression of PDGF and the physiologic equilibrium (homeostasis) of bone metastases associated with advanced prostate cancer.

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