Your SlideShare is downloading. ×
  • Like
Metformin and cancer  journal club
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×

Now you can save presentations on your phone or tablet

Available for both IPhone and Android

Text the download link to your phone

Standard text messaging rates apply

Metformin and cancer journal club

  • 341 views
Published

 

Published in Health & Medicine
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
    Be the first to like this
No Downloads

Views

Total Views
341
On SlideShare
0
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
14
Comments
0
Likes
0

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

  • 1. JOURNAL CLUB 01/03/2012DEPARTMENT OF MEDICAL ONCOMADRAS MEDICAL COLLEGECHENNAI DR. R. RAJKUMAR
  • 2. METFORMIN AND CANCER 1970-PROFESSOR VLADIMIR DILMAN METFORMIN AS GEROPROTECTORS (METABOLIC REHABILITATION) & ANTI CANCER DRUGS. 2000-ANISIMOV- PETROV INSTITUTE OF ONCOLOGY -chronic treatment of female transgenic HER2/neu mice -↓mammary adeno carcinomas. “HYBRID ANTI CANCER PILL”- ↓ INSULIN &GLUCOSE , ↓ AMPK/mtor/S6K1 AXIS
  • 3. METFORMIN AND CANCER• BIGUANIDES- metformin, phenformin and buformin- herb GALEGA OFFICINALIS (French lilac)• MECHANISM OF ACTION- DIRECT-INSULIN INDEPENDENT ACTIVATES AMPK –Energy sensor INDIRECT- INSULIN DEPENDENT
  • 4. METFORMIN AND CANCER
  • 5. DANDELION HYPOTHESIS
  • 6. PATIENTS AND METHODS 3412 patients¹- Neo-adjuvant chemo-Jan 1990- May 2007. 291- Diabetic Exclusion Criteria- Diabetes diagnosed after neo-chemo Resolved GDM Male sex Unknown ER, PR, Her-2 status ˃ 9 months between neo -chemo and surgery Second primary cancer Final study population- 68 Diabetic population(met) ,87(non met), 2374(Non Diabetic) ¹-Breast Cancer Management Database- University of Texas
  • 7. PATHOLOGY Diagnosis- Core- needle biopsy Histology- WHO classification Tumor Grade- modified Blacks nuclear grading IHC- nuclear grading >10%- positive Her-2 status- IHC or FISH HER -2 positive- 3 +
  • 8. TREATMENT 3-6 courses of Anthracycline based chemo-FAC, AC, FEC Add Taxane based chemo–1909 patients(75.5%) Def. Surgery at the end of NACT. All patients- Axillary Staging & SLNB Radiation - Standard Hormonal- ER/PR status
  • 9. STATISTICAL ANALYSIS χ² test of independence Multivariate logistic regression model
  • 10. RESULTS Median Age- 49 years (21- 87) Diabetic Group- Older, Obese , Post- Meno HbA1c- No Difference Insulin Use ˃ Met Group(16%v 33%, p=.02) Neo-Taxane Use ˃ Diabetic Group (87%=Met, 84%=Non Met, 75%=Non Diab,p=.01) 90% - Planned cycles of chemo
  • 11. METFORMIN AND pCR RATES PCR Rate- MetGrop=24%;95%CI,(13%-34%) Non-Met=8.0%;95%CI,(2.3%-14%) Non-Diab=16%;95%CI(15%-18%) ( P=.02 ) Met &Non Met P=.007 Non Met & Non Diab P=.04 Met & Non Diabetic P=.10(non signfi)
  • 12. SURVIVAL ESTIMATES Median Follow-up- 37 months 3yr RFS- 76%(95%CI),66%(95%CI),73%(95%CI) P=.66( Not Significant) OS- 81%(95%CI),78%(95%CI),86%(95%CI) P=.02(Significant)
  • 13. RATE OF PCR Met Group- Insulin v Non Insulin Use 27% v 23%; P=.75 Non Met - Insulin v Non Insulin Use 0% v 12%; P=.05
  • 14. METFORMIN AND CANCERADVANTAGES-1. INEXPENSIVE- GENERIC2. WIDE THERAPEUTIC-TOXIC RATIO3. BROAD SPECTRUM ANTICANCER PILL4. SAFE IN POOR P.S. PATIENTS5. SAFELY COMBINED WITH CHEMO6. METRONOMIC THERAPY7. CHEMO-PREVENTION
  • 15. HORMETIC PHENOMENON
  • 16. THANK YOU