Download Bruera G et al, BMC Cancer 2010

Rome, October 19, 2012
Supportive and Palliative Care in the Elderly
Chemotherapy-related toxicity in the elderly
Gastro-intestinal toxicity
Gemma Bruera
Medical Oncology
Dpt. Biotechnological and Applied Clinical Sciences
University of L'Aquila
Gastrointestinal toxicity in elderly patients
Outline

Decision-making according to patient fitness

Age

Comorbidities

Modulation of treatment according to patients’ fitness

Balance between intensification of medical treatment and
safety (gastro-intestinal toxicity)

Treatment of diarrhea
2
Metastatic colorectal cancer
Integration between antitumoral treatment and
supportive care
ANTITUMORAL
TREATMENT
SUPPORTIVE
CARE
3
AGE
NUTRITIONAL
CONDITION
ADL
IADL
COMORBIDITY
PS
4
Metastatic colorectal cancer
Functional condition of the patient

Elderly patients

Comorbidities

Nutritional conditions

Functional conditions and Performance Status
5
Metastatic colorectal cancer
Functional condition of the patient
Number of comorbidities
Comorbidity
Severity of comorbidities
6
Metastatic colorectal cancer
Comorbidity index CIRS
(Cumulative Illness Rating Scale)
7
Comorbidity index CIRS
8
Activities of
daily living:
ADL
9
Instrumental
activities of
daily living:
IADL
10
Metastatic colorectal cancer
Comorbidities index CIRS
Making decision
Stage
Primary
Characteristics
Independent IADL (score  8)
Absent or mild CIRS
Intermediate Stable CIRS (< 3 mild or moderate
cathegories)

dependent
or
independent IADL
Unstable CIRS ( 3 cathegories or 1
Secondary
severe cathegory)  dependent
IADL
Terminal
11
Metastatic colorectal cancer
Comorbidity index CIRS
(Cumulative Illness Rating Scale)
Primary
Intermediate
Secondary
Terminal
Medical treatments
65-75 years
>75 years
Standard
Standard
Standard
Modified
Modified
Modified
-
12
Gastrointestinal toxicity in elderly patients
Outline

Decision-making according to patient fitness

Age

Comorbidities

Modulation of treatment according to patients’ fitness

Balance between intensification of medical treatment and
safety (gastro-intestinal toxicity)

Treatment of diarrhea
13
Triplet chemotherapy: activity and efficacy data
Phase
ORR
(%)
PFS
(months)
OS
(months)
doublet
triplet
doublet
triplet
doublet
triplet
FOLFOXIRI versus FOLFIRI
Falcone, J Clin Oncol 2007
III
34
60*
6.9
9.8*
16.7
23.4*
FOLFOXIRI versus FOLFIRI
Souglakos, Br J Cancer 2006
III
33.6
43
6.9
8.4
19.5
21.5
FIr/FOx
Morelli, Oncol Rep 2010
II
66.7
12
20
Abbreviations: ORR, objective response rate, PFS, progression-free survival, OS, overall survival,
*, statistically significant difference.
Ficorella C, Bruera G et al, Clin Colorectal Cancer 2012 Epub Ahead of print
14
Triplet chemotherapy:
projected/received dose-intensities
Phase
irinotecan
(mg/m2/week)
oxaliplatin
(mg/m2/week)
5-fluorouracil
(mg/m2/week)
pDI
rDI
%
pDI
rDI
%
pDI
rDI
%
FOLFOXIRI versus FOLFIRI
Falcone, J Clin Oncol 2007
III
82.5
67.65
83
42.5
35.2
82
1600
1312
82
FOLFOXIRI versus FOLFIRI
Souglakos, Br J Cancer 2006
III
65
63.75
85
32.5
27.3
84
1000
880
88
FIr/FOx
Morelli, Oncol Rep 2010
II
80
65.6
82
40
35
87.5
1800
1476
82
Abbreviation: pDI, projected dose-intensity; rDI, received dose-intensity.
Ficorella C, Bruera G et al, Clin Colorectal Cancer 2012 Epub Ahead of print
15
Triplet chemotherapy:
grade 3-4 toxicity (NCI-CTC version 3.0)
Phase
NCI-CTC, version 3.0
FOLFOXIRI versus FOLFIRI
Falcone, J Clin Oncol 2007
III
FOLFOXIRI versus FOLFIRI
Souglakos, Br J Cancer 2006
III
FIr/FOx
Morelli, Oncol Rep 2010
II
Diarrhea
(%)
Stomatitis
Mucositis
(%)
Asthenia
(%)
G3
G4
G3
G4
G3
G4
17
3
4
1
6
-
Neutropenia
(%)
Febrile
neutropenia
(%)
G3
G4
33
17
Neurotoxicity
(%)
G3
G4
2
-
5
27.7
35
5
-
-
5.6
-
4
35
7
-
13
-
5.8
4
-
4
-
Abbreviation: NCI-CTC, National Cancer Institute-Common Toxicity Criteria; G, grade.
Ficorella C, Bruera G et al, Clin Colorectal Cancer 2012 Epub Ahead of print
16
FOLFOXIRI versus FOLFIRI in the elderly MCRC patients
Patients’
features
Vamvakas L et al, Crit Rev Oncol Hematol 2010; 76(1):61-70
17
FOLFOXIRI versus FOLFIRI in the elderly MCRC patients
Age distribution of elderly patients
Vamvakas L et al, Crit Rev Oncol Hematol 2010; 76(1):61-70
18
FOLFOXIRI versus FOLFIRI in the elderly MCRC patients
TTP
OS
Median TTP and OS according to age in patients treated with FOLFIRI
Vamvakas L et al, Crit Rev Oncol Hematol 2010; 76(1):61-70
19
FOLFOXIRI versus FOLFIRI in the elderly MCRC patients
TTP
OS
Median TTP and OS according to age in patients treated with FOLFOXIRI
Vamvakas L et al, Crit Rev Oncol Hematol 2010; 76(1):61-70
20
FOLFOXIRI versus FOLFIRI in the elderly MCRC patients
Forest Plot analysis for OS and TTP
Vamvakas L et al, Crit Rev Oncol Hematol 2010; 76(1):61-70
21
FOLFOXIRI versus FOLFIRI in the elderly MCRC patients
Relative dose-intensities according to age in patients treated with
FOLFIRI and FOLFOXIRI
Vamvakas L et al, Crit Rev Oncol Hematol 2010; 76(1):61-70
22
FOLFOXIRI versus FOLFIRI in the elderly MCRC patients
Incidence of common toxicities according to age in patients treated with
FOLFIRI and FOLFOXIRI
Vamvakas L et al, Crit Rev Oncol Hematol 2010; 76(1):61-70
23
FOLFOXIRI versus FOLFIRI in the elderly MCRC patients
Incidence of common toxicities according to age in patients treated with
FOLFIRI and FOLFOXIRI
Vamvakas L et al, Crit Rev Oncol Hematol 2010; 76(1):61-70
24
MCRC: Intensive 4-drugs chemotherapy
phase II studies: activity and efficacy
ORR
(%)
PFS
(months)
OS
(months)
Triplet regimens 39.0-66.0
8.3-10.6
20.4-26.1
Triplet+Bev
77-82
12-13.1
28-30.9
Triplet+Cet
79
14
37
Abbreviation: Bev, Bevacizumab; Cet, Cetuximab; ORR,
objective response rate; PFS, progression-free survival;
OS, overall survival.
Bruera and Ricevuto, Expert Opin Biol Ther 2011; 11(6):821-4
25
Triplet chemotherapy plus target agent:
activity and efficacy data
Phase
ORR
(%)
PFS
(months)
OS
(months)
FOLFOXIRI + bevacizumab
Masi, Lancet Oncol 2010
II
77
13.1
30.9
FIr-B/FOx
Bruera, BMC Cancer 2010
II
82
12
28
Chrono-IFLO + cetuximab
Garufi, Br J Cancer 2010
II
79
14
37
ERBIRINOX
Assenat, The Oncologist 2011
II
80.9
9.5
24.7
Abbreviations: ORR, objective response rate, PFS, progression-free survival,
OS, overall survival.
Ficorella C, Bruera G et al, Clin Colorectal Cancer 2012 Epub Ahead of print
26
Triplet chemotherapy plus target agent:
projected/received dose-intensities
Phase
irinotecan
(mg/m2/week)
oxaliplatin
(mg/m2/week)
5-fluorouracil
(mg/m2/week)
bevacizumab
(mg/kg/week)
cetuximab
(mg/m2/week)
pDI
rDI
pDI
rDI
pDI
rDI
pDI
rDI
FOLFOXIRI + BEV
Masi,
Lancet Oncol 2010
II
82.5
70
42.5
36
1600
1344
2.5
2
FIr-B/FOx
Bruera,
BMC Cancer 2010
II
80
66
40
32.5
1800
1500
2.5
2
Chrono-IFLO +
cetuximab
Garufi,
Br J Cancer 2010
II
65
55
40
28
1200
1100
250
250
ERNIRIXOX
Assenat,
The Oncologist 2011
II
90
77.4
42.5
36
1400
1288
250
235
Abbreviation: pDI, projected dose-intensity; rDI, received dose-intensity.
27
Ficorella C, Bruera G et al, Clin Colorectal Cancer 2012 Epub Ahead of print
Triplet chemotherapy plus target agent:
grade 3-4 toxicity (NCI-CTC version 3.0)
Phase
NCI-CTC,
version 3.0
Diarrhea
(%)
Asthenia
(%)
G3
G4
G3
G4
14
-
7
-
Neutropenia
(%)
Febrile
neutropenia
(%)
G3
G4
25
25
Hypertension
(%)
Deep-vein
thrombosis
(%)
Cutaneous
Rash
(%)
G3
G4
G3
G4
G3
G4
9
2
7
-
n.r.
n.r.
FOLFOXIRI + BEV
Masi,
Lancet Oncol 2010
II
FIr-B/FOx
Bruera,
BMC Cancer 2010
II
28
-
6
-
10
-
2
-
-
-
n.r.
n.r.
Chrono-IFLO +
cetuximab
Garufi,
Br J Cancer 2010
II
35
1
12
-
6
-
n.r.
n.r.
n.r.
n.r.
15
-
ERBIRINOX
Assenat,
The Oncologist 2011
II
52.4
-
31.7
-
16
4.8
16
-
-
-
-
14.4
-
2
Abbreviation: NCI-CTC, National Cancer Institute-Common Toxicity Criteria; G, grade.
28
Ficorella C, Bruera G et al, Clin Colorectal Cancer 2012 Epub Ahead of print
Toxicity requiring treatment modulation in triplet
chemotherapy plus Bevacizumab reported regimens
NCI-CTC Grade 2-4 (%)
FOLFOXIRI+Bevacizumab
FIr-B/FOx
Number of patients
57
50
Nausea
37
36
Vomiting
28
16
Diarrhea
37
52
Stomatitis/mucositis
28
10
Asthenia
40
46
Neurotoxicity
44
10
Hypertension
21
10
Hypertransaminasemy
n.r.
Anemia
44
8
Leucopenia
n.r.
34
Neutropenia
68
38
Febrile neutropenia
2
-
Thrombocytopenia
3.5
2
9
-
10.5
-
Deep-vein thrombosis
Serious Adverse Events
Abbreviation: NCI-CTC, National Cancer Institute Common Toxicity Criteria; n.r., not reported.
Bruera and Ricevuto, Exper Opin Biol Ther 2011; 11(6):821-4
29
Gastrointestinal toxicity in elderly patients
Outline

Decision-making according to patient fitness

Age

Comorbidities

Modulation of treatment according to patients’ fitness

Balance between intensification of medical treatment and
safety (gastro-intestinal toxicity)

Treatment of diarrhea
30
Poker Schedule (FIr-B/FOx)

5-Fluorouracil (5-FU), time flat infusion of 12h, Irinotecan (CPT-11) / Bevacizumab
(BEV), Oxaliplatin (l-OHP), as first line treatment of metastatic colorectal cancer:
fase II study.
Bev 5 mg/kg
Bev 5 mg/kg
Bruera G et al, BMC Cancer 2010;10:567
Patients and methods  Poker Schedule (FIr-B/FOx)
31
Patients’ features
Total N. (%)
No. of patients
Sex
M/F
50
31/19
Age, years
median
range
> 65 years
63
40-73
24 (48)
WHO Performance Status
0
1-2
48 (96)
2 (4)
Metastatic disease
metacronous
sincromous
15 (30)
35 (70)
Primary tumor
colon
rectum
24 (48)
26 (52)
Sites of metastases
liver
lung
lymph nodes
local
Other
33 (66)
10 (20)
17 (34)
10 (20)
5 (10)
No. of involved sites
1
2
32 (64)
18 (36)
Single metastatic site
liver
lung
lymph nodes
local
22
3
3
4
Liver metastases
single
Multiple
11 (22)
22 (44)
(44)
(6)
(6)
(8)
Previous adjuvant chemotherapy:
FA/5-FU bolus
Capecitabine
Folfox4
9 (18)
4 (8)
1 (2)
4 (8)
Previous radiotherapy:
RT alone
RT+CT (5-FU i.c.)
RT+CT (XELOX)
6 (12)
2 (4)
3 (6)
1 (2)
Abbreviation: WHO, Wordl Health Organization;
c.i., continous infusion
Patients and methods  Patients’ features
32
Bruera G et al, BMC Cancer 2010;10:567
Activity and efficacy data
Intent-to-treat
Analysis
As-treated
Analysis
No
%
No
%
Enrolled patients
50
100
50
100
Evaluable patients
49
98
43
86
Objective Response
Partial Response
Complete Response
40
36
4
82 (CI±11)
73
8
36
32
4
84 (CI±11)
75
9
Stable Disease
2
4
2
5
Progressive Disease
7
14
5
12
12
3-69+
44
88
28
3+-69+
33
66
Median Progressio-free survival, months
Range
Progression events
Median Overall Survival, months
Range
Deaths
Liver metastasectomies
No/Overall patients (50)
No/Patients with liver metastases (33)
No/Patients with liver-only metastases (22)
Results  Activity and efficacy
13
26
39
54
Bruera G et al, BMC Cancer 2010;10:567
33
Kaplan-Meier survival estimate.
Phase II study population; median follow-up 28 months
(1) Progression-Free Survival (2) Overall Survival
(1)
(2)
12 months (3-69+)
31 months (3+-69+)
Bruera G et al, unpublished data
Results  Activity and Efficacy of FIr-B/FOx association
34
Dose-intensity
All patients
Young-elderly patients
DI/cycle
mg/m2(or Kg)/w
DI/cycle
mg/m2(or Kg)/w
Projected DI
mg/m2(or
Kg)/w
Median
(Range)
Received DI
(%)
Median
(Range)
Received DI
(%)
1800
1487
(480-1800)
82,6
1420
(480-1800)
80
CPT-11
80
66,7
(25-80)
83
61
(25-80)
76
l-OHP
40
32
(8-40)
80
31,5
(8-40)
79
BEV
2,5
2,1
(1-2,5)
84
2
(1-2,5)
80
5-FU
Abbreviation: DI, dose-intensity; 5-FU, 5-Fluorouracil; CPT-11, Irinotecan; l-OHP, Oxaliplatin;
BEV, Bevacizumab.
Bruera G et al, BMC Cancer 2010;10:567
Results  Dose-intensity
35
Cumulative toxicity
Patients
Cycles
50
247
Number
NCI-CTC Grade
1
2
3
4
1
2
3
4
Nausea (%)
23 (46)
15 (30)
3 (6)
-
81 (33)
23 (9)
4 (2)
-
Vomiting (%)
10 (20)
6 (12)
2 (4)
-
19 (8)
9 (4)
2 (1)
-
Diarrhea (%)
20 (40)
12(24)
14 (28)
-
76 (30)
28 (11)
15 (6)
-
2 (4)
1 (2)
-
-
2 (1)
1 (0.5)
-
-
Constipation (%)
17 (34)
1 (2)
-
-
22 (9)
1 (0.5)
-
-
Stomatitis/mucositis (%)
16 (32)
2 (4)
3 (6)
-
29 (12)
3 (1)
3 (1)
-
Erythema (%)
1 (2)
-
1 (2)
-
3 (1)
-
1 (0.5)
-
Asthenia (%)
13 (26)
20 (40)
3 (6)
-
48 (19)
38 (15)
3 (1)
-
Neurotoxicity (%)
36(72)
5 (10)
-
-
126(51)
6 (2)
-
-
Hypertension (%)
15 (30)
4 (8)
1 (2)
-
27 (11)
4 (2)
1 (0.5)
-
Hypotension (%)
1 (2)
-
-
-
1 (0.5)
-
-
-
Hematuria (%)
2 (4)
1 (2)
-
-
3 (1)
1 (0.5)
-
-
7 (14)
-
-
-
10 (4)
-
-
-
Rhinitis (%)
38 (76)
-
-
-
110(44.5)
-
-
-
Epistaxis (%)
31 (62)
2 (4)
-
-
68 (27.5)
2 (1)
-
-
2 (4)
-
-
-
2 (1)
-
-
-
6 (12)
-
-
-
9 (4)
-
-
-
Hypokalemia (%)
3 (6)
-
1 (2)
-
3 (1)
-
1 (0.5)
-
Hypertransaminasemy (%)
3 (6)
2 (4)
1 (2)
1 (2)
9 (4)
6 (2)
1 (0.5)
1 (0.5)
6 (12)
2 (4)
-
-
14 (6)
5 (2)
-
-
10 (20)
-
-
-
10 (4)
-
-
-
5 (10)
9 (18)
3 (6)
-
11 (4)
17 (7)
7 (3)
-
Hypoalbuminemia (%)
Gengival recession/gengivitis (%)
HFS (%)
Headache (%)
Hyperpigmentation (%)
Fever without infection (%)
Alopecia (%)
Results  Toxicity
Bruera G et al, BMC Cancer 2010;10:567
36
Cumulative toxicity
Patients
Cycles
50
247
Number
NCI-CTC Grade
1
2
3
4
1
2
3
4
7 (14)
4 (8)
-
-
16 (6)
4 (2)
-
-
Leucopenia (%)
13 (26)
17 (34)
-
-
49 (20)
26(10.5)
-
-
Neutropenia (%)
9 (18)
14 (28)
5 (10)
-
35 (14)
32 (13)
8 (3)
-
Trhombocitopeny (%)
7 (14)
1 (2)
-
-
16 (6)
1 (0.5)
-
-
Anemia (%)
Bruera G et al, BMC Cancer 2010;10:567
Results  Toxicity
37
Cumulative toxicity (young-elderly patients)
Patients
Cycles
24
119
Number
NCI-CTC Grade
1
2
3
4
1
2
3
4
Nausea (%)
8 (33)
10 (42)
2 (8)
-
39 (33)
16 (13)
2 (2)
-
Vomiting (%)
6 (25)
3 (12.5)
2 (8)
-
14 (12)
5 (4)
2 (2)
-
Diarrhea (%)
11 (46)
7 (29)
6 (25)
-
46 (39)
14 (12)
7 (6)
-
1 (4)
1 (4)
-
-
1 (1)
1 (1)
-
-
Constipation (%)
11 (46)
-
-
-
14 (12)
-
-
-
Stomatitis/mucositis (%)
9 (37.5)
1 (4)
3 (12.5)
-
18 (15)
2 (2)
3 (2.5)
-
Erythema (%)
-
-
1 (4)
-
1 (1)
-
1 (1)
-
Asthenia (%)
6 (25)
10 (42)
3 (12.5)
-
21 (18)
22 (18)
3 (2.5)
-
Neurotoxicity (%)
18 (75)
3 (12.5)
-
-
61 (51)
3 (2.5)
-
-
Hypertension (%)
5 (21)
2 (8)
-
-
9 (7.5)
2 (2)
-
-
Hypotension (%)
1 (4)
-
-
-
1 (1)
-
-
-
-
1 (4)
-
-
-
1 (1)
-
-
4 (17)
-
-
-
5 (4)
-
-
-
Rhinitis (%)
20 (83)
-
-
-
45 (38)
-
-
-
Epistaxis (%)
17 (71)
-
-
-
38 (32)
-
-
-
-
-
-
-
-
-
-
-
5 (21)
-
-
-
7 (6)
-
-
-
Hypokalemia (%)
2 (8)
-
-
-
2 (2)
-
-
-
Hypertransaminasemy (%)
1 (4)
1 (4)
-
1 (4)
1 (1)
2 (2)
-
1 (1)
3 (12.5)
-
-
-
5 (4)
-
-
-
6 (25)
-
-
-
6 (5)
-
-
-
3 (12.5)
7 (29)
3 (12.5)
-
8 (7)
14 (12)
7 (6)
-
Hypoalbuminemia (%)
Hematuria (%)
Gengival recession/gengivitis (%)
HFS (%)
Headache (%)
Hyperpigmentation (%)
Fever without infection (%)
Alopecia (%)
Results  Toxicity
Bruera G et al, BMC Cancer 2010;10:567
38
Cumulative toxicity (young elderly patients)
Patients
Cycles
24
119
Number
NCI-CTC Grade
1
2
3
4
1
2
3
4
Anemia (%)
3 (12.5)
2 (8)
-
-
7 (6)
2 (2)
-
-
Leucopenia (%)
9 (37.5)
10 (42)
-
-
33 (38)
15 (13)
-
-
Neutropenia (%)
4 (17)
10 (42)
3 (12.5)
-
25 (21)
23 (19)
3 (2.5)
-
Trhombocitopeny (%)
4 (17)
1 (4)
-
-
6 (5)
1 (1)
-
-
Bruera G et al, BMC Cancer 2010;10:567
Results  Toxicity
39
Limiting toxicity syndromes (LTS):
overall and in young-elderly patients
Overall
Young-elderly
No
%
No
%
Patients
50
100
24
100
Limiting Toxicity Syndromes (LTS)
22
44
11
46
LTS single-site (LTS-ss)
10
20
2
8
LTS multiple-sites (LTS-ms)
12
24
9
37.5
Single DLT plus G2-3
10
20
7
29
2
4
2
8
Double DLTs
Abbreviation: DLT, dose-limiting toxicity; G, grade
Bruera G et al, BMC Cancer 2010;10:567
Results  Toxicity
40
Limiting Toxicity Syndromes (LTS)
Patients
#
Age
(years)
Associated Toxicity
DLT
DLT
G2-G3
1
51
Diarrhea G3
-
-
2
62
Diarrhea G3
-
-
3
71
Diarrhea G3
-
-
4
62
Diarrhea G3
-
-
5
58
Diarrhea G3
-
-
6
70
Asthenia G3
-
-
7
62
Hypertension G3
8
51
Hypertransaminasemy G3
-
-
9
55
Thrombocytopeny G1 for >2 weeks
-
-
10
63
Neutropenia G3
-
-
11
68
Diarrhea G3
-
Vomiting G3
12
59
Diarrhea G3
-
13
67
Diarrhea G3
-
14
57
Diarrhea G3
-
Vomiting G2
Neurotoxicity G2
Nausea G3
Asthenia G2
Nausea G3
15
67
Diarrhea G3
-
Vomiting G2
16
65
Diarrhea G3
17
40
Diarrhea G3
-
Nausea G2
18
66
Diarrhea G3
-
19
67
Stomatitis/mucositis G3
-
Stomatitis/mucositis G2
Asthenia G2
Asthenia G2
20
66
Hypertransaminasemy G4
-
21
71
Diarrhea G3
Stomatitis/mucositis G3
Diarrhea G2
Nausea G2
Anemia G2
Hypoalbuminemia G2
Erythema G3
-
22
66
Stomatitis/mucositis G3
Abbreviation: DLT, dose-limiting toxicity; G, grade.
Results  Toxicity
Epistaxis G2
Bruera G et al, BMC Cancer 2010;10:567 41
Poker-C Schedule (FIr-C/FOx-C)

5-Fluorouracil (5-FU), time flat infusion of 12h, Irinotecan (CPT-11) / Cetuximab
(Cet), Oxaliplatin (l-OHP), as first line treatment of metastatic colorectal cancer:
fase II study.
Medical Oncology, S. Salvatore Hospital, University of L'Aquila, Preliminary unpublished data
Patients and methods  Poker Schedule (FIr-C/FOx-C)
42
Dose-intensity
All patients
Young-elderly patients
DI/cycle
mg/m2(or Kg)/w
DI/cycle
mg/m2(or Kg)/w
Projected DI
mg/m2(or
Kg)/w
Median
(Range)
Received DI
(%)
Median
(Range)
Received DI
(%)
1800
1440
(214.25-1800)
80
977.5
(675-1280)
54
CPT-11
80
60
(20-80)
75
48
(40-56)
60
l-OXP
40
32
(10-40)
80
21
(10-32)
52.5
250
200
(93-287.5)
80
171.25
(112.5-230)
58
5-FU
Cet
Abbreviation: DI, dose-intensity; 5-FU, 5-Fluorouracil; CPT-11, Irinotecan; l-OHP, Oxaliplatin;
Cet, Cetuximab.
Medical Oncology, S. Salvatore Hospital, University of L'Aquila, Preliminary unpublished data
Results  Dose-intensity
43
Limiting toxicity syndromes (LTS):
overall and in young-elderly patients
Overall
Young-elderly
No
%
No
%
Patients
9
100
2
100
Limiting Toxicity Syndromes (LTS)
7
78
1
50
LTS single-site (LTS-ss)
-
-
-
-
LTS multiple-sites (LTS-ms)
7
78
1
50
Single DLT plus G2-3
4
44
-
-
Double DLTs
3
33
1
50
Abbreviation: DLT, dose-limiting toxicity; G, grade
Medical Oncology, S. Salvatore Hospital, University of L'Aquila, Preliminary unpublished data
Results  Toxicity
44
Limiting Toxicity Syndromes (LTS)
Patients Age
#
(years)
1
54
Associated Toxicity
DLT
G2-G3
DLT
Skin rash G3
Stomatitis/mucositis G3
Asthenia G2
Diarrhea G2
2
60
Diarrhea G3
Constipation G2
Asthenia G2
Neurotoxicity G2
Hypotension G2
Stomatitis/mucositis G2
3
51
Diarrhea G3
Stomatitis/mucositis G2
Asthenia G2
Neurotoxicity G2
Rhinitis G2
4
56
Diarrhea G3
Nausea G2
Anorexia G2
Hypertension G2
Fever without infection G2
Skin rash G2
Stomatitis/mucositis G2
5
59
Diarrhea G3
Deep vein thrombosis
Dry skin G2
Erythema G2
6
72
Myocardial infarcion
Diarrhea G2
Vomiting G2
7
58
Diarrhea G3
Asthenia G3
Anorexia G3
Hypercreatininemia G2
Hyponatriemia G3
Results  Toxicity
Hypoalbuminemia G245
Abbreviation: DLT, dose-limiting toxicity; G, grade.
Gastrointestinal toxicity in elderly patients
Outline

Decision-making according to patient fitness

Age

Comorbidities

Modulation of treatment according to patients’ fitness

Balance between intensification of medical treatment and
safety (gastro-intestinal toxicity)

Treatment of diarrhea
46
Diarrhea: treatment

Patients without risk of complications:

I step: initial dose loperamide 4 mg + 2 mg after each
episode of diarrhea (maximum daily dose 16 mg)

II step, in case of diarrhea unchanged after 12-24 hours:
Loperamide 2 mg after each episode of diarrhea +
fluoroquinolone

III step, in case of diarrhea unchanged after 12-24
hours: Octreotide 0.6 mg sc continuos infusion for 24
hours + rehidration iv.
Rosenoff Sh et al, J Support Oncol 2006; 4:289-294
Alimonti A et al, Cancer Treat Rev 2004; 30:555-562
Benson AB et al, J Clin Oncol 2004; 22:2918-2926
Rubenstein EB et al, Cancer 2004; 100(10):2026-2046
Javle MM et al, Clin Cancer Res 2007; 13:965-971
Porzio G et al, La terapia dei sintomi in oncologia, SCTF, Oncologia Medica L’Aquila
47
Diarrhea: treatment

Patients at risk of complications (G3-4 diarrhea, or G1-2 diarrhea
associated with nausea/vomito ≥G2, fever, neutropenia,
dehydration, comorbidity, liver failure, chronic renal failure,
diabetes, heart disease):

IV hydration

Antibiotic (fluoroquinolone iv)

I step: Octreotide 0.6 mg sc continuos infusion for 24 hours

II step: Octreotide 0.9 mg sc continuos infusion for 24 hours

III step: add atropine 0.5 mg sc every 4/6 hours (not in
patients with heart diseases or glaucoma) or atropine 2 mg sc
continuos infusion for 24 hours.
Stein A et al, Ther Adv Med Oncol 2010; 2(1):51-63
Peeters M et al, Acta Gastroenterol Belg 2010; 73:25-36
Cherny NI, J Pain Symptom Manage 2008; 36:413-423
Gilbson RJ et al, Supp Care Cancer 2006; 14:890-900
Porzio G et al, La terapia dei sintomi in oncologia, SCTF, Oncologia Medica L’Aquila
48
Diarrhea: prevention

Patients receiving chemotherapy with previous G3-4
diarrhea or G2-4 diarrea with concomitant diseases (liver
failure, chronic renal failure, diabetes, heart disease)


I step: octreotide LAR

30 mg im 14 days before day1 of therapy

30 mg im day1 of therapy

30 mg im every 28 days
II step: octreotide LAR 40 mg im + celecoxib 400 mg x2.
Rosenoff Sh et al, J Support Oncol 2006; 4:289-294
Alimonti A et al, Cancer Treat Rev 2004; 30:555-562
Benson AB et al, J Clin Oncol 2004; 22:2918-2926
Rubenstein EB et al, Cancer 2004; 100(10):2026-2046
Javle MM et al, Clin Cancer Res 2007; 13:965-971
Porzio G et al, La terapia dei sintomi in oncologia, SCTF, Oncologia Medica L’Aquila
49
Conclusions

Parameters to guarantee proper balance between treatment
efficacy and safety

Age (young-elderly, old-elderly)

Comorbidity (CIRS)

Cumulative toxicity

Limiting toxicity syndromes (individual toxicity)

Received dose-intensity

Activity and efficacy
50