Genitourinary Cancer: Poster Discussion

1
Genitourinary Cancer Poster Discussion

• Ian F Tannock MD, PhD
• Daniel E Bergsagel Professor of Medical Oncology
• Princess Margaret Hospital and University of
  Toronto

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Potential conflicts of interest

• I have no financial conflicts of interest
• I and my colleagues entered patients in the
  randomised trial comparing sutinib with
  interferon-?

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Prostate Cancer

• K. Chi et al (CUOG), Vancouver, Canada
• A phase 2 study of patupilone in patients with
  metastatic hormone refractory prostate cancer who
  have progressed after docetaxel

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Background and Rationale

• Docetaxel is usual initial chemotherapy in
  patients with Castrate-Resistant Prostate Cancer
  (CRPC)
• No effective 2nd line treatment.
• Patupilone (Epothilone B) is a microtubule
  targeting agent, which is active agianst a broad
  spectrum of cell lines in vitro and in vivo
• A prior phase II study of weekly patupilone in
  men with CRPC showed PSA response in 25, some
  after taxane-based chemotherapy
• This phase II study evaluates 3-weekly patupilone
  in men with metastatic CRPC who had progressed
  after docetaxel

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Study Design
1o Endpoint
Stage I

• CRPC
• Progression while on or within 6 months of
  docetaxel

Patupilone 10 mg/m2 (first 6 pts) and 8 mg/m2
(pts 7)
Accrue 43 evaluable patients if gt6 responses
open Stage II

• PSA response
• 50 decline from baseline, confirmed 3 weeks

Stage II
2o Endpoints
After 6 responses

• Response ratio/duration
• Time to progression
• Time to treatment failure
• Overall survival
• Pain intensity index and analgesic score
• Safety and tolerability

Accrue 28 additional patients if gt14 responses
further studies warranted
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Adverse Events

• Four first-cycle serious GI adverse events
  (diarrhea, dehydration, ileus) occurred in the
  first 6 patients who received 10 mg/m2
• Initial dose then lowered to 8 mg/m2 with
  improved tolerability
• No Grade 3 or 4 hematologic adverse events
• Fatigue, diarrhea and anorexia remained most
  frequent grade 3 events

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Efficacy Summary

• 70 patients evaluable for PSA response
• Preliminary assessments shows 50 decline in PSA
  in 31/70 (44) patients
• Confirmed PSA response in 22/70 (31) patients
• Of 59 patients eligible for analysis 32 (54) had
  a pain response (defined as a 2 point decrease or
  disappearance of pain on a 6 point scale)
• Too early to comment on Time to Progression or
  survival

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Waterfall Plot of PSA Decline
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My Comments

• Patupilone is active but has substantial GI
  toxicity
• Epothilones are neurotoxic and perhaps not ideal
  agents for use after docetaxel
• A randomised phase 2 study of another epothilone
  (ixabepilone) showed similar PSA response rates
  to mitoxantrone (17 20) in men who had prior
  taxane (Rosenberg et al Cancer 2007110556-63)
• A planned phase 3 trial of ixabepilone was
  abandoned.
• I have limited enthusiasm for a phase 3 second-
  line study of patupilone