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Transcript of Gemma Bruera Medical Oncology Dpt. Biotechnological and Applied Clinical Sciences University of...
Gemma BrueraMedical OncologyDpt. Biotechnological and Applied Clinical SciencesUniversity of L'Aquila
Rome, October 19, 2012
Supportive and Palliative Care in the Elderly
Chemotherapy-related toxicity in the elderly
Gastro-intestinal toxicity
2
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
Gastrointestinal toxicity in elderly patientsOutline
3
Metastatic colorectal cancerIntegration between antitumoral treatment and supportive care
ANTITUMORAL
TREATMENT
SUPPORTIVE CARE
5
Elderly patients
Comorbidities
Nutritional conditions
Functional conditions and Performance Status
Metastatic colorectal cancerFunctional condition of the patient
6
Number of comorbidities
Severity of comorbidities
Comorbidity
Metastatic colorectal cancerFunctional condition of the patient
11
Terminal
Unstable CIRS ( 3 cathegories or 1 severe cathegory) dependent IADL
Secondary
Stable CIRS (< 3 mild or moderate cathegories) dependent or independent IADL
Intermediate
Independent IADL (score 8) Absent or mild CIRS
PrimaryCharacteristicsStage
Metastatic colorectal cancerComorbidities index CIRS Making decision
12
Medical treatments 65-75 years >75 years Primary Standard Standard Intermediate Standard Modified Secondary Modified Modified Terminal - -
Metastatic colorectal cancerComorbidity index CIRS (Cumulative Illness Rating Scale)
13
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
Gastrointestinal toxicity in elderly patientsOutline
14
Triplet chemotherapy: activity and efficacy data
Phase ORR(%)
PFS(months)
OS(months)
doublet triplet doublet triplet doublet triplet
FOLFOXIRI versus FOLFIRIFalcone, J Clin Oncol 2007
III 34 60* 6.9 9.8* 16.7 23.4*
FOLFOXIRI versus FOLFIRISouglakos, Br J Cancer 2006
III 33.6 43 6.9 8.4 19.5 21.5
FIr/FOxMorelli, 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
15
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 FOLFIRIFalcone, J Clin Oncol 2007
III 82.5 67.6583
42.5 35.282
1600 131282
FOLFOXIRI versus FOLFIRISouglakos, Br J Cancer 2006
III 65 63.7585
32.5 27.384
1000 88088
FIr/FOxMorelli, Oncol Rep 2010
II 80 65.682
40 3587.5
1800 147682
Abbreviation: pDI, projected dose-intensity; rDI, received dose-intensity.
Ficorella C, Bruera G et al, Clin Colorectal Cancer 2012 Epub Ahead of print
16
Triplet chemotherapy: grade 3-4 toxicity (NCI-CTC version 3.0)
Phase Diarrhea(%)
StomatitisMucositis
(%)
Asthenia(%)
Neutropenia(%)
Febrile neutropenia
(%)
Neurotoxicity(%)
NCI-CTC, version 3.0 G3 G4 G3 G4 G3 G4 G3 G4 G3 G4
FOLFOXIRI versus FOLFIRIFalcone, J Clin Oncol 2007
III 17 3 4 1 6 - 33 175
2 -
FOLFOXIRI versus FOLFIRISouglakos, Br J Cancer 2006
III 27.7 5 5.6 357
5.8
FIr/FOxMorelli, Oncol Rep 2010
II 35 - - - 4 - 13-
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
17
FOLFOXIRI versus FOLFIRI in the elderly MCRC patients
Patients’ features
Vamvakas L et al, Crit Rev Oncol Hematol 2010; 76(1):61-70
18
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
19
FOLFOXIRI versus FOLFIRI in the elderly MCRC patients
Median TTP and OS according to age in patients treated with FOLFIRI
TTP OS
Vamvakas L et al, Crit Rev Oncol Hematol 2010; 76(1):61-70
20
FOLFOXIRI versus FOLFIRI in the elderly MCRC patients
Median TTP and OS according to age in patients treated with FOLFOXIRI
TTP OS
Vamvakas L et al, Crit Rev Oncol Hematol 2010; 76(1):61-70
21
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
22
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
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
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
25
MCRC: Intensive 4-drugs chemotherapyphase 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
26
Triplet chemotherapy plus target agent: activity and efficacy data
Phase ORR(%)
PFS(months)
OS(months)
FOLFOXIRI + bevacizumabMasi, Lancet Oncol 2010
II 77 13.1 30.9
FIr-B/FOxBruera, BMC Cancer 2010
II 82 12 28
Chrono-IFLO + cetuximabGarufi, Br J Cancer 2010
II 79 14 37
ERBIRINOXAssenat, 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
27
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 + BEVMasi, Lancet Oncol 2010
II 82.5 70 42.5 36 1600 1344 2.5 2
FIr-B/FOxBruera, BMC Cancer 2010
II 80 66 40 32.5 1800 1500 2.5 2
Chrono-IFLO + cetuximabGarufi, Br J Cancer 2010
II 65 55 40 28 1200 1100 250 250
ERNIRIXOXAssenat,The Oncologist 2011
II 90 77.4 42.5 36 1400 1288 250 235
Abbreviation: pDI, projected dose-intensity; rDI, received dose-intensity.
Ficorella C, Bruera G et al, Clin Colorectal Cancer 2012 Epub Ahead of print
28
Triplet chemotherapy plus target agent: grade 3-4 toxicity (NCI-CTC version 3.0)
Phase Diarrhea(%)
Asthenia(%)
Neutropenia(%)
Febrile neutropenia
(%)
Hypertension(%)
Deep-veinthrombosis
(%)
CutaneousRash(%)
NCI-CTC, version 3.0
G3 G4 G3 G4 G3 G4 G3 G4 G3 G4 G3 G4
FOLFOXIRI + BEVMasi, Lancet Oncol 2010
II 14 - 7 - 25 252
9 2 7 - n.r. n.r.
FIr-B/FOxBruera, BMC Cancer 2010
II 28 - 6 - 10 - 2 - - - n.r. n.r.
Chrono-IFLO + cetuximabGarufi, Br J Cancer 2010
II 35 1 12 - 6 - n.r. n.r. n.r. n.r. 15 -
ERBIRINOXAssenat,The Oncologist 2011
II 52.4 - 31.7 - 164.8
16 - - - - 14.4 -
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
29
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
Deep-vein thrombosis 9 -
Serious Adverse Events 10.5 -
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
30
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
Gastrointestinal toxicity in elderly patientsOutline
31
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.
Patients and methods Poker Schedule (FIr-B/FOx)
Bev 5 mg/kg Bev 5 mg/kg
Bruera G et al, BMC Cancer 2010;10:567
32
Patients’ features Total N. (%)
No. of patients 50
Sex M/F 31/19
Age, years median range > 65 years
6340-73
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 (44)3 (6)3 (6)4 (8)
Liver metastases single Multiple
11 (22)22 (44)
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’ featuresBruera G et al, BMC Cancer 2010;10:567
33
Activity and efficacy data
Results Activity and efficacy
Intent-to-treatAnalysis
As-treatedAnalysis
No % No %
Enrolled patients 50 100 50 100
Evaluable patients 49 98 43 86
Objective Response Partial Response Complete Response
40364
82 (CI±11)738
36324
84 (CI±11)759
Stable Disease 2 4 2 5
Progressive Disease 7 14 5 12
Median Progressio-free survival, months Range Progression events
123-69+
44 88
Median Overall Survival, months Range Deaths
283+-69+
33 66
Liver metastasectomies No/Overall patients (50) No/Patients with liver metastases (33) No/Patients with liver-only metastases (22)
13263954
Bruera G et al, BMC Cancer 2010;10:567
34
Kaplan-Meier survival estimate. Phase II study population; median follow-up 28 months (1) Progression-Free Survival (2) Overall Survival
(1)
12 months (3-69+)
(2)
31 months (3+-69+)
Results Activity and Efficacy of FIr-B/FOx association
Bruera G et al, unpublished data
35
Dose-intensity
Results Dose-intensity
All patients Young-elderly patients
DI/cyclemg/m2(or Kg)/w
DI/cyclemg/m2(or Kg)/w
Projected DImg/m2(or Kg)/w
Median(Range)
Received DI (%)
Median(Range)
Received DI (%)
5-FU 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
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
36
Cumulative toxicity
Results Toxicity
Patients Cycles
Number 50 247
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) -
Hypoalbuminemia (%) 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) - -
Gengival recession/gengivitis (%) 7 (14) - - - 10 (4) - - -
Rhinitis (%) 38 (76) - - - 110(44.5) - - -
Epistaxis (%) 31 (62) 2 (4) - - 68 (27.5) 2 (1) - -
HFS (%) 2 (4) - - - 2 (1) - - -
Headache (%) 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)
Hyperpigmentation (%) 6 (12) 2 (4) - - 14 (6) 5 (2) - -
Fever without infection (%) 10 (20) - - - 10 (4) - - -
Alopecia (%) 5 (10) 9 (18) 3 (6) - 11 (4) 17 (7) 7 (3) -
Bruera G et al, BMC Cancer 2010;10:567
37
Cumulative toxicity
Results Toxicity
Patients Cycles
Number 50 247
NCI-CTC Grade 1 2 3 4 1 2 3 4
Anemia (%) 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) - -
Bruera G et al, BMC Cancer 2010;10:567
38
Cumulative toxicity (young-elderly patients)
Results Toxicity
Patients Cycles
Number 24 119
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) -
Hypoalbuminemia (%) 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) - - -
Hematuria (%) - 1 (4) - - - 1 (1) - -
Gengival recession/gengivitis (%) 4 (17) - - - 5 (4) - - -
Rhinitis (%) 20 (83) - - - 45 (38) - - -
Epistaxis (%) 17 (71) - - - 38 (32) - - -
HFS (%) - - - - - - - -
Headache (%) 5 (21) - - - 7 (6) - - -
Hypokalemia (%) 2 (8) - - - 2 (2) - - -
Hypertransaminasemy (%) 1 (4) 1 (4) - 1 (4) 1 (1) 2 (2) - 1 (1)
Hyperpigmentation (%) 3 (12.5) - - - 5 (4) - - -
Fever without infection (%) 6 (25) - - - 6 (5) - - -
Alopecia (%) 3 (12.5) 7 (29) 3 (12.5) - 8 (7) 14 (12) 7 (6) -
Bruera G et al, BMC Cancer 2010;10:567
39
Cumulative toxicity (young elderly patients)
Results Toxicity
Patients Cycles
Number 24 119
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
40
Limiting toxicity syndromes (LTS): overall and in young-elderly patients
Results Toxicity
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
Double DLTs 2 4 2 8
Abbreviation: DLT, dose-limiting toxicity; G, grade
Bruera G et al, BMC Cancer 2010;10:567
41
Limiting Toxicity Syndromes (LTS)
Results Toxicity
Patients#
Age(years) DLT
Associated Toxicity
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 - Vomiting G2 Neurotoxicity G2
13 67 Diarrhea G3 - Nausea G3Asthenia G2
14 57 Diarrhea G3 - Nausea G3
15 67 Diarrhea G3 - Vomiting G2
16 65 Diarrhea G3 Epistaxis G2
17 40 Diarrhea G3 - Nausea G2
18 66 Diarrhea G3 - Stomatitis/mucositis G2Asthenia G2
19 67 Stomatitis/mucositis G3 - Asthenia G2
20 66 Hypertransaminasemy G4 - Diarrhea G2Nausea G2Anemia G2
21 71 Diarrhea G3 Stomatitis/mucositis G3 Hypoalbuminemia G2
22 66 Stomatitis/mucositis G3 Erythema G3 -
Abbreviation: DLT, dose-limiting toxicity; G, grade.
Bruera G et al, BMC Cancer 2010;10:567
42
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.
Poker-C Schedule (FIr-C/FOx-C)
Patients and methods Poker Schedule (FIr-C/FOx-C)
Medical Oncology, S. Salvatore Hospital, University of L'Aquila, Preliminary unpublished data
43
Dose-intensity
Results Dose-intensity
All patients Young-elderly patients
DI/cyclemg/m2(or Kg)/w
DI/cyclemg/m2(or Kg)/w
Projected DImg/m2(or Kg)/w
Median(Range)
Received DI (%)
Median(Range)
Received DI (%)
5-FU 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
Cet 250 200(93-287.5)
80 171.25(112.5-230)
58
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
44
Limiting toxicity syndromes (LTS): overall and in young-elderly patients
Results Toxicity
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
45
Limiting Toxicity Syndromes (LTS)
Results Toxicity
Patients#
Age(years) DLT
Associated ToxicityDLT G2-G3
1 54 Skin rash G3 Stomatitis/mucositis G3 Asthenia G2Diarrhea G2
2 60 Diarrhea G3 - Constipation G2Asthenia G2
Neurotoxicity G2Hypotension G2
Stomatitis/mucositis G23 51 Diarrhea G3 - Stomatitis/mucositis G2
Asthenia G2Neurotoxicity G2
Rhinitis G24 56 Diarrhea G3 - Nausea G2
Anorexia G2Hypertension G2
Fever without infection G2Skin rash G2
Stomatitis/mucositis G25 59 Diarrhea G3 Deep vein thrombosis Dry skin G2
Erythema G26 72 Myocardial infarcion - Diarrhea G2
Vomiting G27 58 Diarrhea G3 Asthenia G3 Anorexia G3
Hypercreatininemia G2Hyponatriemia G3
Hypoalbuminemia G2 Abbreviation: DLT, dose-limiting toxicity; G, grade.
46
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
Gastrointestinal toxicity in elderly patientsOutline
47
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.
Diarrhea: treatment
Rosenoff Sh et al, J Support Oncol 2006; 4:289-294Alimonti A et al, Cancer Treat Rev 2004; 30:555-562
Benson AB et al, J Clin Oncol 2004; 22:2918-2926Rubenstein EB et al, Cancer 2004; 100(10):2026-2046
Javle MM et al, Clin Cancer Res 2007; 13:965-971Porzio G et al, La terapia dei sintomi in oncologia, SCTF, Oncologia Medica L’Aquila
48
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.
Diarrhea: treatment
Stein A et al, Ther Adv Med Oncol 2010; 2(1):51-63Peeters M et al, Acta Gastroenterol Belg 2010; 73:25-36
Cherny NI, J Pain Symptom Manage 2008; 36:413-423Gilbson 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
49
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.
Diarrhea: prevention
Rosenoff Sh et al, J Support Oncol 2006; 4:289-294Alimonti A et al, Cancer Treat Rev 2004; 30:555-562
Benson AB et al, J Clin Oncol 2004; 22:2918-2926Rubenstein EB et al, Cancer 2004; 100(10):2026-2046
Javle MM et al, Clin Cancer Res 2007; 13:965-971Porzio G et al, La terapia dei sintomi in oncologia, SCTF, Oncologia Medica L’Aquila