University hospital „Carl Gustav Carus“ Dresden, Germany · University hospital „Carl Gustav...
Transcript of University hospital „Carl Gustav Carus“ Dresden, Germany · University hospital „Carl Gustav...
University hospital „Carl Gustav Carus“Dresden, Germany
Colorectal carcinoma:
Adjuvant treatment in the elderly
Gunnar Folprecht
Adjuvant Chemotherapy for Colon Cancer
Moertel et al NEJM 1990
Would you recommend adjuvant chemotherapy?
• a 78 year old woman with pT4pN1M0 G3 with some comorbidities…
• a 84 year old man with pT3pN2M0 G3 with average comorbidity for the age…
Sargent – NEJM 2001
7 studies ⋅ 3351 patients ⋅ 506 Patienten ≥ 70 years
Colon cancer stage II – III
NEJM 2001
Overallsurvival
Freedom fromrecurrence
> 70 y.n=506
< 70 y.n=2745
Sargent, NEJM 2001
69%
62%
71%
64%
Grade 3/4 toxicity of adjuvant 5-FU treatment
5-FU/ FAVomiting/Nausea 5% 2% 0.15Diarrhea 15% 15% 0.99Stomatitis 11% 15% 0.21Leukopenia 4% 8% 0.05
5-FU/ LevamisolVomiting/Nausea 7% 9% 0.37Diarrhea 9% 11% 0.44Stomatitis 5% 9% 0.09Leukopenia 17% 31% 0.001
< 70 y. > 70 y. p
Sargent NEJM 2001
Royal Marsden Hospital: Toxicity of adjuvant 5-FU
< 70 y. > 70 y. pn 419 124- bolus (pts) 208 49- infus. (pts) 211 75
Grade 3/4Diarrhea 11% 9% 0.5Stomatitis 11% 19% 0.02Vomiting/Nausea 2% 3% 0.8Infection 3% 7% 0.97Fever 0 1% 0.9Neutropenia 29% 35% 0.2
Popescu, JCO 1999
X-ACT- Study: Capecitabine vs. 5-FU/FA
HR 0.87 (0.75-1.0) p=.053 HR 0.84 (0.69-1.0) p=.071
Overall survival Disease free survival
1.987 patients, Stage IIIN1 70-71%, N2 29-30%median age 62 – 63 year Twelves, NEJM 2005
X-ACT- Study: Capecitabine vs. 5-FU/FA
1.987 patients, Stage III
HR 0.84 (0.69-1.0) p=.071
Overall survival Disease free survival
N1 70-71%, N2 29-30%median age 62 – 63 year Twelves, NEJM 2005
MOSAIC-trial: LV5FU2 ± Oxaliplatin
Andre, NEJM 2004
HR 0.77p=0.002
40% stage II
5-FU/FA: 72.9%(70.2-75.7%; n=1123)
FOLFOX: 78.2%(75.6-80.7%; n=1123)
Disease free survival
UICC II / III RFOLFOX
OP
LV5FU2
Survival: Adjuvant FOLFOX vs. 5-FU/FA
deGramont, ASCO 2007
Elderly pts: 5-FU +/- Oxaliplatin
< 70 years ≥70 years
Goldberg, JCO 2006
Toxicity
Recurrence after resection of colon cancer
ACCENT database, Sargent JCO 2007
Frequency of adjuvant chemotherapy in elderly patients
0102030405060708090
100
% 78 74 58 34 11 2
65-69 70-74 75-79 80-84 85-89 >=90age
%
1991 - 1996
6262 pts.
Schrag, JNCI 2001
Patients receiving adjuvant therapy
Colon cancer stage IIIData from 560 hospital based cancer registries
Jessup, JAMA 2005
Age distribution in adjuvant trials
5-FU vs. obs FOLFOX vs 5-FUSargent
Age distribution in SEER database
Iwashyna, JCO 2002
Relationship: Comorbidity and tumor stage
Read JCO 2004
Comorbidity and ageFrequency of
adjuvant chemotherapy
0
5
10
15
20
25
30
35
>64y >69y >74y >79y >84y
all causes chemo complications
Frequency of HOSPITALISATION
0
10
20
30
40
50
60
70
80
90
>64y >69y >74y >79y >84y
0 comorb 1 comorb >1 comorb
Edwards, JNCI 2005
Completion of adjuvant chemotherapyrate of
Age % of pts completionof adjuvant CTx
total 100% 78.2%66-70 30.8% 82.4%71-75 33.6% 80.7%76-80 24.7% 74.4%81-85 9.3% 67.6%≥86 1.6% 64.7%
unadjust.CTX cancer adjusted RR
mortality
none 31.0% 1.00incomplete 30.4% 0.94 (0.81-1.11)complete 24.2% 0.79 (0.69-0.89)
Dobie, JNCI 2006
Adjuvant treatment in elderly patients
Iwashyna, JCO 2002
Population based data
4768 patients in SEER- data base
Sundararajan,Ann Int Med. 2002
Would you recommend adjuvant chemotherapy?
• a 78 year old woman with pT4pN1M0 G3 with some comorbidities…
• a 84 year old man with pT3pN2M0 G3 with average comorbidity for the age…
MAGIC- study
Cunningham, NEJM 2006
PFS Overall survival
Population bases data
4768 patients in SEER- data base
Sundararajan,Ann Int Med. 2002