ACSO annual meeting update no. 2

There were a significant number of prostate cancer poster presentations today (Saturday), many giving information about small Phase II clinical trials of investigational drugs in advanced and hormone-refractory prostate cancer (HRPC).

There appear to be no new data from large, randomized phase III clinical trials in prostate cancer expected at ASCO this year, so the Phase II data presented below may be among the more interesting and really “new” prostate cancer data available from this meeting:

  • A Phase II study of a nanocrystalline formulation of  2-methoxyestradiol (Panzem®) in 21 patients with HRPC who had already failed taxane therapy showed no significant clinical activity, although the drug was well tolerated and did show signals of biological activity.
  • A Phase II trial of azacitidine (Vidaza®) suggested the possibility that this drug may have clinical activity in patients who are progressing on combined androgen blockade and who have not received any prior form of chemotherapy. However, the evidence is limited at this time, and we would expect at least a randomized Phase II clinical trial to be necessary before a Phase III trial could be considered.
  • Another Phase II trial showed preliminary efficacy data for the investigational drug patupilone (an epothilone) in patients with HRPC who have progressed after treatment with docetaxel (Taxotere®). This trial has enrolled 77 patients to date, and efficacy data were presented on 40 of these patients. The drug appeared to be reasonably well tolerated at a dosing regimen of 8 mg/m2 every 3 weeks.
  • A second investigational epothilone, sagopilone (also known as ZK-EPO) was tested with prednisone as first line chemotherapy for patients with metastatic HRPC. Again, there was some evidence of biological activity, and this trial will continue to enroll patients.
  • Dasatinib (Sprycel™) 100 mg twice a day (b.i.d.) was used as a single agent in a Phase II trial to treat 70 patients with HRPC prior to any other form of chemotherapy. A range of measurable responses included reductions in PSA levels, reductions in markers for bone metabolism, and stable bone scan data. A significant number of patients needed a reduction in their daily dose from 100 mg b.i.d. to 70 mg b.i.d.
  • An investigational platinum-based agent called picoplatin was tested in Phase I and Phase II trials in combination with docetaxel and prednisone in chemotherapy-naive patients with metastatic HRPC. Of 26 patients evaluable for a PSA response, 69 percent showed a significant drop in their PSA.
  • Ketoconazole together with lenolidomide (Revlimid®) was tested in a Phase II trial in 30 evaluable patients with HRPC. This combination of drugs was relatively well tolerated, and there was objective evidence of antitumor activity. In particular there was a significant decline in PSA (up to a 90 percent decline) in nearly 60 percent of patients. A randomized Phase II trial of this combination is now being investigated.
  • A 177-lutetium radiolabeled anti-prostate-specific membrane antigen known as 177-Lu-J591 was tested in a Phase II trial in patients with metastatic HRPC. The drug was well tolerated, successfully targeted known sites of metastatic prostate cancer, and resulted in PSA declines in more than 50 percent of the patients. Further trials of this agent are planned in M0 and bulky M1 disease.
  • Finally, a phase II trial of sunitinib (Sutent®) in combination with docetaxel and prednisone was conducted in 38 patients with metastatic HRPC. The combination appeared to be reasonably well tolerated by most patients, and the majority of patients showed a considerable reduction in the PSA levels. Again, the current trial will continue to accrue patients through about late June. If this trial continues to demonstrate promising results, we may see a randomized Phase II trial of this combination initiated later in 2008.

As can be seen from the comments above, several new agents have shown some degree of activity in the treatment of late stages of prostate cancer. However, the degree of activity is limited, and The “New” Prostate Cancer InfoLink would be wary of too much optimism based on any of these data.

Having said that, given the limited effectiveness of the only currently available drug combinations in  treatment of metastatic, hormone-refractory disease, any small advance would represent a significant clinical benefit, and so it is exciting to see the number of agents now being tested in late stage disease.

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