JOURNAL CLUB        01/03/2012DEPARTMENT OF MEDICAL ONCOMADRAS MEDICAL COLLEGECHENNAI   DR. R. RAJKUMAR
METFORMIN AND CANCER 1970-PROFESSOR VLADIMIR DILMAN  METFORMIN AS GEROPROTECTORS  (METABOLIC REHABILITATION) & ANTI  CANC...
METFORMIN AND CANCER• BIGUANIDES- metformin, phenformin  and buformin- herb GALEGA  OFFICINALIS (French lilac)• MECHANISM ...
METFORMIN AND CANCER
DANDELION HYPOTHESIS
PATIENTS AND METHODS 3412 patients¹- Neo-adjuvant chemo-Jan 1990-  May 2007. 291- Diabetic Exclusion Criteria-      Dia...
PATHOLOGY Diagnosis- Core- needle biopsy Histology- WHO classification Tumor Grade- modified Blacks nuclear  grading I...
TREATMENT 3-6 courses of Anthracycline based  chemo-FAC, AC, FEC Add Taxane based chemo–1909  patients(75.5%) Def. Surg...
STATISTICAL ANALYSIS χ² test of independence Multivariate logistic regression model
RESULTS Median Age- 49 years (21- 87) Diabetic Group- Older, Obese , Post-  Meno HbA1c- No Difference Insulin Use ˃ Me...
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%-...
SURVIVAL ESTIMATES Median Follow-up- 37 months 3yr RFS-  76%(95%CI),66%(95%CI),73%(95%CI)  P=.66( Not Significant) OS- ...
RATE OF PCR Met Group- Insulin v Non Insulin Use                27% v 23%; P=.75 Non Met - Insulin v Non Insulin Use    ...
METFORMIN AND CANCERADVANTAGES-1. INEXPENSIVE- GENERIC2. WIDE THERAPEUTIC-TOXIC RATIO3. BROAD SPECTRUM ANTICANCER PILL4. S...
HORMETIC PHENOMENON
THANK YOU
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
Metformin and cancer  journal club
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Metformin and cancer journal club

  1. 1. JOURNAL CLUB 01/03/2012DEPARTMENT OF MEDICAL ONCOMADRAS MEDICAL COLLEGECHENNAI DR. R. RAJKUMAR
  2. 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. 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. 4. METFORMIN AND CANCER
  5. 5. DANDELION HYPOTHESIS
  6. 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. 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. 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. 9. STATISTICAL ANALYSIS χ² test of independence Multivariate logistic regression model
  10. 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. 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. 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. 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. 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. 15. HORMETIC PHENOMENON
  16. 16. THANK YOU

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