Noscapine and Prostate Cancer

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Noscapine and Prostate Cancer
Israel Barken M.D. Prostate Cancer Research and
Education Foundation
www.PCREF.org 619-461-8181
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What is Noscapine?

• Noscapine and Codeine are natural compounds
  isolated from opium in 1817. (Pierre-Jean
  Robiquet)
• Noscapine is a non-addictive derivative of Opium.
  
• Noscapine is a very safe cough suppressant.
• Noscapine is an anti-tubulin drug.

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History of Noscapine

• In the 19th century it was considered an
  anti-malarial drug.
• In 1930 it was discredited as anti-malarial
  drug.
• Noscapine has very slight analgesic effect.
• Noscapine acts synergistically to increase the
  sedative effects of morphium. (3 fold).

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History of Noscapine

• 1930 Noscapines antitussive effect is
  suggested, especially for bronchial asthma.
• 1959 - it was recommended to replace codeine.
• Since 1960 - Noscapine is widely used as an
  antitussive medication.

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History of Noscapine

• Europe
• Japan
• North and South America
• South Africa
• World Health Organization Formulary

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History of Noscapine

• Orally
• Tablets
• Capsules
• Lozenges
• Syrup
• Rectally in suppository form

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Anti Cancer Effects Discovered

• 1958- Cell cultures performed at the United
  States National Cancer Institute
• Significant cytotoxic properties
• Not patentable at that time
• No more research funded

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Safety and side effects of noscapine

• Extensive toxicology studies carried out in both
  animals and humans have confirmed its extremely
  low toxicity with little or no effect on vital
  organs and blood parameters, and with negligible
  side effects.

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Safety and side effects of Noscapine

• In 1961, a toxicity study on terminally ill
  cancer patients was carried out at Johns Hopkins
  University.
• Daily doses of up to 3,000 mg,
• 80 of patients experienced no side effects
• 20 experienced mild sedation and abdominal
  discomfort.

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Off label use of Noscapine

• Off label use of drugs is common.
• Noscapine off label use
• Anecdotal experience
• Compassionate use study by FDA approval

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Noscapine Today

• 1997- Keqiang Ye and Dr. Harish Johsi Professor
  of cell biology, Emory University
• Noscapine reduced breast cancer volume by 80 in
  3 weeks ( animal models)
• Noscapine shows little or no toxicity to liver,
  kidney, heart, bone marrow, small intestine.
• No inhibition of immune responses

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Noscapine Today

• Conclusion
• Noscapine has the potential to be an effective
  chemotherapeutic agent for the treatment of human
  cancer.
• Question
• Why not study Prostate Cancer?

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Noscapine Inhibits Human Prostate Cancer
Progression and Metastasis in the Mouse Model
The 17th International Prostate Cancer Update
Conference Vail Colorado Feb 15th 2007

• Israel Barken, M.D.
• The Prostate Cancer Research and Education
  Foundation

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Table 1 Average Body weight in each group
Table 1 Average body weight in each group
Group No. of animals evaluated Mean body weight at sacrifice (g) ? SD P value
Vehicle 8 ml/kg 10 23.7 ? 2.9 -
Noscapine 300 mg/kg 10 24.4 ? 4.0 gt0.05
P value
Mean body weight at sacrifice (g) ? SD
No. of animals evaluated
Group
-
23.7 ? 2.9
10
Vehicle 8 ml/kg
gt0.05
24.4 ? 4.0
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Noscapine 300 mg/kg
Table1. The relatively stable bodyweight in the
Noscapine 300 mg/kg treated group during the
dosing period indicated that the compound tested
had no significant toxicity.
Table1. The relatively stable bodyweight in the
Noscapine 300 mg/kg treated group during the
dosing period indicated that the compound tested
had no significant toxicity.
Table1. The relatively stable bodyweight in the
Noscapine 300 mg/kg treated group during the
dosing period indicated that the compound tested
had no significant toxicity.
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Table 2 Average tumor volume in each group
Group No of animals evaluated Mean tumor volume at sacrifice mm3 P Value
Vehicle 8ml/Kg 10 1047.6 /- 288.2
Noscapine 10 421.2 /- 259 lt0.001
The treated group compared to vehicle control by
the Students t-test (two-sided, ?0.05).
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Table 3 Average metastatic tumor weight in each
group
Group No of animals evaluated Mean metastatic tumor weight P Value
Vehicle 8ml/Kg 10 0.25/- 0.25
Noscapine 300mg/Kg 10 0.05/-0.11 ,0.001
At time of sacrifice
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Table 4 Average total tumor Weight in each
group
Vehicle 10 ml/kg 10 0.97 ? 0.31 -
Noscapine 300 mg/kg 10 0.42? 0.23 lt0.001
The treated group compared to vehicle control by
the Students t-test (two-sided, ?0.05).
The treated group compared to vehicle control by
the Students t-test (two-sided, ?0.05).
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Figure 1 Primary Tumor Growth
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The advantages of Noscapine

• Oral use
• Non toxic
• Anti Cancer Activity
• Over the counter status
• Long history of use as a drug

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The disadvantages of Noscapine

• Patent issues
• Availability issue
• Lack of funds for clinical studies
• Prostate Cancer does not seem to be a priority
  of cancer researchers.

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The FDA
www.fda.org/cder/offices/OPS_IO/MRTD.HTM www.fda.org/cder/offices/OPS_IO/MRTD.HTM www.fda.org/cder/offices/OPS_IO/MRTD.HTM
MRTD   (mg/kg-  bw/day)   Generic Chemical Name Chemical Structure
2.50000 Noscapine C1(OC)C5C(CC2C1OCO2)CCN(C)C5C3OC(O)C4C3CCC(OC)C4OC
Maximum Recommended Therapeutic Dose (MRTD)
Database
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The FDA

• www.fda.gov/cder/offices/OTC_Ingredient_List_D-O.p
  df

noscapine cough/cold (antitussive) 52 FR 30054
noscapine hydrochloride cough/cold (antitussive) 52 FR 30054
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The future

• New way of doing research - Web based patient
  driven data collection system.
• Exclusion and inclusion criteria are post
  participation.
• Every file is included in the large database.
• Every participant gets to have a chart to
  follow.
• Every researcher gets data base access.

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The future

• I am calling on physicians and patients alike to
  help PC-REF launch the project.
• I ask each patient to work with his physician.
• I ask each patient to create a Medical Smart
  Chart.
• There will be an Ask Dr. Barken show dedicated
  to Noscapine.

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Take calculated risks
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Thank You
Stay tuned