# Presentation: 154712

## Second-line Chemotherapy for Hormone Refractory Prostate CancerDisease Background

**Nicholas J. Vogelzang, MD**
**Director****Nevada Cancer Institute**

**CD-1**

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## Prostate Cancer Mortality in the United States

**In 2007 27,050 US men will die from metastatic prostate cancer**
**Second leading cause of cancer death among US men**
**~ 90% with bone metastases**
**Painful and debilitating illness**

**American Cancer Society: http://www.cancer.org/downloads/STT/CAFF2007PWSecured.pdf**

**CD-35**

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## Treatment of Prostate Cancer

**Local therapies highly curative**
**A subset of patients develop or present with metastatic disease**
**Initial response to androgen deprivation therapy of 2 to 3 years followed by progression to hormone-refractory state**
**Chemotherapy for men with hormone refractory metastatic prostate cancer **

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## Three Approved Chemotherapy Drugs for Hormone Refractory Prostate Cancer

**1981: Estramustine**
**1996: Mitoxantrone**
**2004: Docetaxel**

**CD-38**

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## HRPC: Docetaxel Therapy Is Not a Cure

**SWOG 9916****a**
**Median PFS**
**Docetaxel + estramustine: 6.3 months**
**Mitoxantrone + prednisone: 3.2 months**
**HR = 0.73 (0.63, 0.86)**
**TAX 327****b**
**Median PFS**
**Docetaxel + prednisone: 6.7 months****c**

**a** **Petrylak D, et al. *****N Engl J Med. *****2004;351:1513-1520.**
**b** **Tannock I, et al. *****N Engl J Med. *****2004;351;1502-1512.**
**C**** ****Unpublished; used by permission of M. Eisenberger.**

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## No Established Second-Line Chemotherapy in HRPC

**Logical extension of clinical research**
**Unmet medical need for a rapidly progressing and debilitating disease ****(median survival = 12 months)**
**No effective regimen in this setting**
**Less than half of patients receive second-line chemotherapy****a**

**a**** ****IntrinsiQ and Decision Resources, 2006.**

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## No Established Second-line Chemotherapy in HRPC

**Mitoxantrone and weekly docetaxel ****most commonly used agents **
**Limited clinical evidence in second-line setting**
**Open field for investigation of new agents**
**Effective and well-tolerated second-line chemotherapy the standard in breast, colon, and lung cancers **
**Second-line regimen in HRPC is an ****unmet medical need**

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## Challenges in Second-line Trials in HRPC

**No prior phase III trials**
**Frail and elderly population with multiple comorbidities**
**Rapidly progressing and debilitating disease**
**Majority of patients with difficult to measure and painful bone lesions**
**Need for composite endpoint including clinically-relevant and objective measures of disease progression, pain, and functional status**

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## CALGB Composite PFS Endpoint

**Three widely used measures of clinical benefit**
**1. Disease progression**
**2. Pain control and opioid analgesic use**
**3. Weight loss or performance status decline**
**Applied to 9 large CALGB trials (first-line) **
**Predictive of overall survival**
**22 months vs 9 months, HR = 0.52, *****p***** < 0.001**

**CD-43**

**Halabi S, et al. ASCO. 2007.**

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## Pain Predicts Overall Survival in Men With HRPC

**CALGB database ~600 patients**
**17.6 months (low pain) vs****10.2 months (high pain); *****p***** < 0.001**
**TAX 327 database of 414 patients**
** ****21.1 months (pain response) vs**** 12.7 months (no pain response); *****p***** < 0.001**

**Halabi S, et al. ASCO. Prostate Cancer Symposium. 2007.****Berthold D, et al. ASCO. 2006.**

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## Pain in Hormone Refractory Prostate Cancer

**Moyad et al. (ASCO 2006)**
_**Survey of 409 HRPC patients**_**:**
**   ****Experienced bone pain all the time or every day ****	****60%**
**   “****Can't do the things I would like”****	****50%**
**   ****Need daily medication to manage pain****	****47%**
**   ****Feel depressed****	****32%**

**Moyad et al. ASCO. 2006, #14505.**

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## In Summary—HRPC Progressing After First-line Chemotherapy

**An unmet medical need**
**A rapidly progressing, debilitating, and ultimately fatal disease**
**Urgent need for effective and well-tolerated therapies**
**Optimal evaluation requires a composite endpoint including measures of pain and tumor progression**

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