Strontium chloride - 89

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Strontium chloride - 89
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Prostate Cancer facts

• At the time of diagnosis
• 75 of patients have locally advanced or
  metastatic disease
• 30 to 50 of patients present bone metastases
• Patients with bone metastases have a median life
  expectancy of greater than 2 years

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Prostate Cancer facts

• Prognosis for advanced or metastatic disease
• Survival median lt 36 months
• 2 year survival rate about 20
• 5 year survival rate about 10
• The treatment objective is PALLIATIVE
• managing painful metastasis
• improving patient condition

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Prostate cancer world mortality
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Palliation treatment options

• Non steroid anti inflammation drugs
• Hormones
• External Beam Radiotherapy
• Opiates
• Biphosphonates
• Radionuclides

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Radionuclides

• The aims of radionuclides
• systemic radiotherapy
• target the metastases specifically
• concentrate radiation at metastases
• long lasting effect
• spare healthy tissues
• good safety profile

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Radionuclides

• Strontium 89
• Samarium 153
• Rhenium 186
• (Phosphorus 32)
• (Tin 117M)

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Metastron set up of indications

• Metastron indications are based on a matrix of
• clinical observation bone pain metastases
• primary cancer site prostate or non prostate
• other radiation treatment options adjunct and/or
  alternative to external beam radiotherapy
• There is no restriction linked to the WHO pain
  ladder

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WHO pain ladder Metastron
Opioid for moderate / severe pain /- non
opioids /- adjuvants
Inadequate pain relief
Opioid for mild / moderate pain /- non
opioids /- adjuvants
non-opioid /- adjuvant
PAIN
Positive bone scan pain Metastron candidate
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Metastron what it is (1)

• Characteristics
• Calcium analogue
• Pure beta emission
• Half life 50.5 days

• Advantages
• Needs no carrier to follow only Ca pathway
• Safe for care providers and relatives.
• Outpatient procedure
• Prolonged irradiation of the metastases, while
  sparing healthy tissues

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Metastron what it is (2)

• Characteristics
• Minimal penetration in soft tissues
• Low energy 4mCi (150MBq)
• Ready to use presentation

• Advantages
• Spares soft tissues
• Good tolerability
• No need to collect body fluids (Safety
  Regulation)
• No need to adapt the dose to the patient

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Metastron what it is (3)

• Characteristics
• 1 single injection in the arm
• Delivers localised radiation therapy

• Advantages
• Increases patients comfort
• Saves travelling hospital time
• No radiation side effects on surrounding tissues

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Metastron where it goes

• Characteristics
• Quickly leaves the blood stream
• Targets and concentrates in bone metastases
• half life in healthy bone of 14 days
• bone metastasis retention quasi indefinite
• bone marrow exposure 1/10 of initial dose

• Advantages
• Minimized radiation risk to soft organs
• Selectively irradiates painful and not painful
  yet bone metastases
• Spares healthy bone and bone marrow

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Metastron efficacy evaluation

• The primary evaluation of response is the
  palliation of bone pain metastases measured by
• doctor and patient appreciation
• reduced intakes of pain killers, including
  opiates !
• improvement in overall mobility
• resume of daily activities
• improvement of sleep pattern
• delayed time for further external beam
  radiotherapy

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Metastron efficacy evaluation

• The primary evaluation of response is the
  palliation of bone pain metastases measured by
• doctor and patient appreciation
• reduced intakes of pain killers, including
  opiates !
• improvement in overall mobility
• resume of daily activities
• improvement of sleep pattern
• delayed time for further external beam
  radiotherapy

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Duration and quality of pain relief
Porter et al 1993
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Pain relief definitions

• EFFICACY I
• Full pain relief , no pain, pain free, overall
  dramatic improvement, complete clinical response
• EFFICACY II
• Substantial to dramatic improvement, marked pain
  relief, meaningful clinical response, remarkable
  improvement
• EFFICACY III
• Some improvement, mild improvement

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Metastron Safety profile

• Characteristics
• Minor reversible haematological side
• effects
• Pain flare may happen during the first few days

• Advantages / Weaknesses
• Very rare clinically significant
• Possible repeated treatment after 3 months
• temporary increase in pain killers

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Repeated treatment and duration of pain relief
Kasalicky et al 1998
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Repeated treatment and quality of pain relief
Kasalicky et al 1998
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Repeated treatment and quality of pain relief
Kasalicky et al 1998
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Patient profile

• Hormone control relapse (Europe)
• Palliative stage of prostate cancer (Europe)
• Life expectancy about 2 years
• Presence and/or progression of bone metastases
  assessed by a bone scan.
• Increasing pain disrupting habits, mobility,
  activity level, comfort and quality of life.

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Metastron benefits to the patient

• Long lasting pain relief up to 6 months
• Delays the development of new sites of pain
• Delays need to further therapy
• Increases mobility
• Possible re-injection, every 3 months
• Does not affect digestion or awareness
• One single injection in the arm
• Outpatient procedure

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Metastron present positioning,

• If Metastron is positioned too late, there are
  major concerns over efficacy and safety
• Efficacy
• The more advanced the disease, the more bone
  metastases to target, the less response to
  treatment for a shorter time (too short life
  expectancy). No alternative relief in case of
  pain flare left !
• Safety
• The more fragile the patient, the more cumulated
  toxicity from previous inadequate treatments.
  Such patients will either be prone to adverse
  reactions, or Metastron will be contra indicated
  because of their overall health situation.

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Issues to be considered when Metastron is
positioned very late.
Pain flare Toxicity
Life expectancy Pain relief Pain flare relief
options
Benefice / risk ratio for the targeted population
Risk of adverse events of patients not
eligible spinal cord compression hematological
profile life expectancy lt 3 months insufficient
bone marrow function
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Metastron, positioning(2)

• Metastron needs to be positioned
• Adjuvant or alternative to external beam
  radiotherapy for patients with hormone refractory
  prostate cancer when they are symptomatic
• Providing 4 to 6 months of pain relief
• Increasing time to development of new pain sites

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Metastron comparison pharmacological data
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Metastron comparison clinical data
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Metastron comparison pharmacological data
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Specific indications of Sr-89 for
hormone-refractory prostate cancer

• Metastatic disease with multiple bone metastases
  associated with pain that becomes refractory to
  hormone treatment.
• Progressive disease sites with pain that are not
  controlled with conventional analgesia.
• Painful sites of disease on both sides of the
  diaphragm.
• Patients or disease factors associated with
  relative contraindication for multiple single
  fields of radiation.
• Patients having no evidence of impending spinal
  cord compression.
• Patients adequately preserving bone marrow
  function.
• Evidence from a diagnostic bone scan of
  radionuclide concentration in a painful bone
  lesion.

2nd International Consultation on Prostate Cancer
- June, 1999
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Management of hormone-refractory prostate cancer

• Guidelines on the management of prostate cancer
• The Royal college of Radiologists clinical
  oncology information network.
• British Association of Urological Surgeons
• Clinical Oncology (1999)11S56, S81-82
• The Royal College of Radiologists

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Management of hormone-refractory prostate cancer
1/3

• Patients with advanced disease must all have
  access to a multidisciplinary team.
• The composition of this multidisciplinary is
• Palliative care specialists
• Oncologists
• Urologists

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Summary

• Highly effective Up to 80 of patients
  experience pain relief after 1 injection
• Long term palliative effect up to 6 months
• Reduction of analgesic intake, incl. opioids
• Quality of life relieves pain, improves sleep
  pattern, mobility, appetite
• Minimal reversible side effects
• Delay in the development of new metastatic sites
• Out patient basis
• Multiple dose possible
• Reduction in treatment costs