slide1
Download
Skip this Video
Download Presentation
Highlights in the Management of Breast Cancer

Loading in 2 Seconds...

play fullscreen
1 / 77

CMF and node positive Patients - PowerPoint PPT Presentation


  • 621 Views
  • Uploaded on

CINBO Consorzio Interuniversitario Nazionale per la Bio-Oncologia. Highlights in the Management of Breast Cancer. “Taxanes vs Anthra-containing chemotherapy in the treatment of early-BC and the issue of cardiac toxicity”. Rome, May 25-26, 2007. Vincenzo Adamo

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'CMF and node positive Patients' - Jimmy


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

CINBO

Consorzio Interuniversitario

Nazionale per la Bio-Oncologia

Highlights in theManagement of

Breast Cancer

“Taxanes vs Anthra-containing chemotherapy in the treatment of early-BC and the issue of cardiac toxicity”

Rome, May 25-26, 2007

Vincenzo Adamo

Oncologia Medica e Terapie Integrate A.O.Universitaria, Policlinico “G. Martino” Messina

slide2

from Lancet ‘98

to Oxford 2000

cmf and node positive patients
CMF and node positive Patients

RFS

HR 0.71, p.005

OS

HR 0.79, p.04

Median Follow up 28.5 yrs

G. Bonadonna,BMJ, Jan 2005

slide5

EBCTCG OVERVIEW 2005 AND ISSUE SYSTEMIC CHEMOTHERAPY

TO CONFIRM

  • To need of adjuvant chemotherapy for early breast cancer
  • A superiority of antrhaciclynes based regimens in adjuvant setting

The Lancet Vol 365 May 14, 2005

slide7

Anthravs otherregimens

5 yr of recurrence

from the EBCTCG (2005)

slide8

Which Anthracycline-basedregimen ?

  • Three-drug regimens
    • CAF>CMF ± Tam(INT 0102)
    • CEF>CMF(NCIC-CTG)
  • Sequential regimen
    • E  CMF > CMF(NEAT-SCTBG BR9601)
  • Two-drug regimens
    • AC = CMF TAM(NSABP B-15, B-23)
    • EC and hEC = CMF(Belgian trial)
slide10

ROLE OF TAXANES IN ADJUVANT SETTING

“Taxanes (Paclitaxel and Docetaxel) with significant antitumoral activity in metastatic disease have been evaluated in the adjuvant setting, and their inclusion can further modify the natural history of the disease by reducing the risk of recurrence and death”

Buzdar AU, et al. editorial JCO2007

slide11

ROLE OF TAXANES IN ADJUVANT SETTING

  • First GenerationTrials: 31000 pts
    • Comparing taxane/anthracycline to non-taxane/anthracycline
      • Sequential (anthra followed by taxane)
      • Combination
  • Second GenerationTrials: 25000 pts
    • Comparing taxanes in both arms
      • Sequential
      • Combination
      • With Herceptin

Nowak AK et al. Lancet Oncol 5: 372–80, 2004

slide13

NSABP B28

N= 3060 N+ pts

P 225mg/m2(3 h)

C 600 mg/m2

NONE

A 60 mg/m2

Recommended

TAM if HR(+)

with chemoRx

Median follow-up

64.8-64.4 months

Mamounas et alJCO 2005

slide14

NSABP B28: Toxicity

*cardiac dysfunction either during or subsequent to therapy

°acute myelogenous leukemia ormyelodysplastic syndrome

**AC: pulmonary embolism in one, congestive heart failure in two, sepsis in one, and seizure in one; AC and PTX: coronary artery disease in one, pulmonary embolism in one.

slide15

CALGB 9344

RR: recurrence

17%

N= 3121 N+ pts

P 175 mg/m2(3 h)

C 600 mg/m2

RR: death

18%

RR:death18%

NONE

A 60= 75= 90 mg/m2

Recommended

TAM if HR(+)

after chemoRx

Median follow-up

69.0 months

Henderson et alJCO 2003

slide16

CALGB 9344: Toxicity

There was no difference in incidence of cardiotoxicity between those who did and those who did not receive paclitaxel.

CHF was observed during active protocol therapy in four (<1%) and six (<1%) pts and during post treatment follow-up in 23 (1%) and 27 (2%) pts randomly assigned to CA alone and CA plus paclitaxel, respectively.

°including high dose of Doxorubicin

slide17

E2197 Trial

Goldstein L,PASCO ’05 abs 512

slide18

E2197:Results I

Goldstein L, PASCO ’05 abs 512

slide19

E2197:Results II

Goldstein L, PASCO ’05 abs 512

slide20

E2197: Toxicity

Goldstein L,PASCO ’05 abs 512

slide21

BCIRG001

Adaptated 26° SABCS 2003

slide22

BCIRG001: post Chemotherapy Treatment

Adaptated 26° SABCS 2003

slide23

BCIRG001: characteristics of the pts and the tumors

Martin M et al N Engl J Med 352; 22, 2, 2005

slide24

Analysis of Survival Rates in the

two Study Groups

Martin M et al N Engl J Med 352; 22, 2, 2005

slide25

Risk Reduction for Disease-free Survival in the Main Subgroups

Martin M et al N Engl J Med 352; 22, 2, 2005

slide26

BCIRG001: toxicity

Martin M et al N Engl J Med 352; 22, 2, 2005

slide27

MDACC TRIAL

Buzdar AU, et al. Clinical Cancer Research 2002

slide28

MDACC TRIAL: Results

ER- pts

RFS all pts

ER+ pts

Buzdar AU etal, Clinical Cancer Research 2002

slide29

MDACC TRIAL: toxicity

Buzdar AU, et al. Clinical Cancer Research 2002

pacs 01
PACS-01

Stratified on:

Center

 Age: < or  50

 N: 1-3;  4

6 FEC-100: ARM A

Fluorouracil 500 mg/m² d1

Epirubicin 100 mg/m² d1

Cyclophosphamide 500 mg/m² d1

6 cycles every 21 days

S

U

R

G

E

R

Y

R

3 FEC-100/3 Docetaxel: ARM B

3 cycles of FEC 100 every 21 days

followed by

3 cycles of Docetaxel 100 mg/m² d1

every 21 days

Radiotherapy delivered within 4 weeks after the last chemotherapy cycle

 Tamoxifen 20 mg/day for 5 years prescribed in hormone-receptor positive

post-menopausal womenafter chemotherapy

slide31

PACS-01:characteristics of pts and tumors

Roché H et al J Clin Oncol 2006

slide32

PACS-01: RESULTS

DFS

OS

Roché H et al J Clin Oncol 2006

slide34

PACS-01:Toxicity

Roché H et al J Clin Oncol 2006

slide35

ECTO Study

Gianni L, et al, Clin Cancer Res 2005

slide36

Patient characteristics and results

Gianni L, et al. Clin Cancer Res 2005

slide37

Main toxicities

Gianni L, et al. Clin Cancer Res 2005

slide38

NCIC CTG MA.21

q 3 w

Pts

N+

or

N-

HRisk

q 3 w

q 2 w

Primary end point: relapse free survival (RFS)

Secondary end-points: overall survival, toxicity and QoL

Burnell M et al. Breast Cancer Res Treat. Abs 53, 2006

slide39

NCIC CTG MA.21: Schedules

CEF = oral cyclophosphamide/epirubicin/5-fluorouracil; AC-T =doxorubicin/cyclophosphamide and paclitaxel; EC-T = epirubicin/cyclophosphamide and paclitaxel;

from medscape: Update on Adjuvant Chemotherapy in BC H McArthur & C Hudis, 2007   

slide40

NCIC CTG MA.21: Results

2104 patients enrolled Dec-2000-April 2005

global test of significance

slide41

NCIC CTG MA.21

However, both the CEF and dose-dense EC-T regimens were associated with increased rates of febrile neutropenia,TVE, and delayed cardiotoxicity compared with AC-T.

slide42

Randomized Trials of Adjuvant Chemotherapy with Taxanes

* parameter after 4 years of follow up

slide43

Cardiac Toxicity

P=0.09

P=1.0

During and posttreat

P=.03

P=.63

P=.09

slide44

Comments

  • Cardiac toxicity data are controversial: most of the trials don’t include a careful cardiac monitoring before, during and after the treatments
  • Many trials demostrate that Anthracyclines and Taxanes are the most active cytotoxic drugs for the treatment of breast cancer also as adjuvant chemotherapy.
  • However the advantages obtained by this combination must be carefully balanced against potential risks, particularly in the adjuvant setting.
slide45

Mechanisms and types of Cardiotoxicity Associated with different therapeutic modalities

by Brian R, et al, Ed Boock ASCO 2007

adjuvant chemotherapy options
Adjuvant Chemotherapy Options

Trastuzumab if HER-2 positive

adapted fromPiccart et al. (2005)

slide65

TC vs AC

Jones S. et al. JCO 2006

slide66

TC vs AC: results I

Jones S. et al. JCO 2006

slide67

TC vs AC: results II

Jones S. et al. JCO 2006

slide68

TC vs AC: toxicity

Jones S. et al. JCO 2006

slide69

Conclusion: Thirty-one years ago, the original AC regimen was reported. Now, there is a superior nonanthracycline regimen, TC.

At 5 years, TC was associated with a superior DFS and a different toxicity profile compared with AC.

Jones S. et al. JCO 2006

slide70

High Risk Patient

provocative new scenarious

HR negative

Node neg/pos

HER2 negative

Topo II positive

HR negative

Node neg/pos

HER2 positive

Topo II negative

HR negative

Node neg/pos

HER2 positive

Topo II positive

HR negative

Node neg/pos

HER2 negative

Topo II negative

FEC

FEC docetaxel

Taxanes(carbo) +

Trastuzumab

FC(caelyx)C +

Trastustumab

Taxanes +

Cyclophosphamide

the end

The End

Stop Here

slide73

Best Use of Taxanes / Anthracyclines

  • When should we offer a Taxane-regimen?
  • Which Taxane:Paclitaxel ? Docetaxel ?
  • Which Regimen: Sequential A(C)T, Combined AT ?
  • Which Antracyclineregimen:(CEF ?)
  • Which Schedule:3 Weekly, Weekly ?
  • Which Patients ?: Role of Predictive Factors
adjuvant taxanes which data from randomized trials
Adjuvant Taxanes : which data from randomized trials
  • Adjuvant taxanes improve DFS

(Level 1 evidence ?)

2 positive trials(CALGB 9344, BCIRG 001)

1 negative trial ( NSABP B-28),but:

TAM concomitant to chemotherapy

TAM to all pt >50 years old

  • Adjuvant Taxanes do not improved OS:

longer follow-up

waiting for ongoing trials results

  • Adjuvant taxanes increase toxicity
slide75

Togliere ???

Slamon “BCIRG 006”, SABCS 2006

slide76

?????

Slamon “BCIRG 006”, SABCS 2006

adjuvant chemotherapy options77
Adjuvant Chemotherapy Options

Trastuzumab if HER-2 positive

CMF ? TAXANES ?

adapted fromPiccart et al. (2005)

ad