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