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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.
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Rome, October 19, 2012 Supportive and Palliative Care in the Elderly Chemotherapy-related toxicity in the elderly Gastro-intestinal toxicity Gemma Bruera MedicalOncology Dpt. Biotechnological and Applied Clinical Sciences Universityof L'Aquila
Gastrointestinal toxicity in elderly patientsOutline • 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
Metastatic colorectal cancerIntegration between antitumoral treatment and supportive care SUPPORTIVE CARE ANTITUMORAL TREATMENT
AGE NUTRITIONAL CONDITION ADL IADL COMORBIDITY PS
Metastatic colorectal cancerFunctional condition of the patient • Elderly patients • Comorbidities • Nutritional conditions • Functional conditions and Performance Status
Metastatic colorectal cancerFunctional condition of the patient Number of comorbidities Comorbidity Severity of comorbidities
Metastatic colorectal cancerComorbidity index CIRS (Cumulative Illness Rating Scale)
Stage Characteristics Primary Independent IADL (score 8) Absent or mild CIRS Intermediate Stable CIRS (< 3 mild or moderate cathegories) dependent or independent IADL Secondary Unstable CIRS ( 3 cathegories or 1 severe cathegory) dependent IADL Terminal Metastatic colorectal cancerComorbidities index CIRS Making decision
Metastatic colorectal cancerComorbidity index CIRS (Cumulative Illness Rating Scale) • Medical treatments • 65-75 years>75 years • Primary Standard Standard • Intermediate Standard Modified • Secondary Modified Modified • Terminal - -
Gastrointestinal toxicity in elderly patientsOutline • 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
Triplet chemotherapy: activity and efficacy data Ficorella C, Bruera G et al, Clin Colorectal Cancer 2012 Epub Ahead of print
Triplet chemotherapy: projected/received dose-intensities Ficorella C, Bruera G et al, Clin Colorectal Cancer 2012 Epub Ahead of print
Triplet chemotherapy: grade 3-4 toxicity (NCI-CTC version 3.0) Ficorella C, Bruera G et al, Clin Colorectal Cancer 2012 Epub Ahead of print
FOLFOXIRI versus FOLFIRI in the elderly MCRC patients Patients’ features Vamvakas L et al, Crit Rev Oncol Hematol 2010; 76(1):61-70
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
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
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
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
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
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
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
MCRC: Intensive 4-drugs chemotherapyphase II studies: activity and efficacy Bruera and Ricevuto, Expert Opin Biol Ther 2011; 11(6):821-4
Triplet chemotherapy plus target agent: activity and efficacy data Ficorella C, Bruera G et al, Clin Colorectal Cancer 2012 Epub Ahead of print
Triplet chemotherapy plus target agent: projected/received dose-intensities 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) 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 Bruera and Ricevuto, Exper Opin Biol Ther 2011; 11(6):821-4
Gastrointestinal toxicity in elderly patientsOutline • 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
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 PokerSchedule (FIr-B/FOx)
Patients’ features Patients and methods Patients’ features Bruera G et al, BMC Cancer 2010;10:567
Activity and efficacy data Bruera G et al, BMC Cancer 2010;10:567 Results Activity and efficacy
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+) Bruera G et al, unpublished data Results Activity and Efficacy of FIr-B/FOx association
Dose-intensity Bruera G et al, BMC Cancer 2010;10:567 Results Dose-intensity
Cumulative toxicity Bruera G et al, BMC Cancer 2010;10:567 Results Toxicity
Cumulative toxicity Bruera G et al, BMC Cancer 2010;10:567 Results Toxicity
Cumulative toxicity (young-elderly patients) Bruera G et al, BMC Cancer 2010;10:567 Results Toxicity
Cumulative toxicity (young elderly patients) Bruera G et al, BMC Cancer 2010;10:567 Results Toxicity
Limiting toxicity syndromes (LTS): overall and in young-elderly patients Bruera G et al, BMC Cancer 2010;10:567 Results Toxicity
Limiting Toxicity Syndromes (LTS) Bruera G et al, BMC Cancer 2010;10:567 Results Toxicity
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 PokerSchedule (FIr-C/FOx-C)
Dose-intensity Medical Oncology, S. Salvatore Hospital, University of L'Aquila, Preliminary unpublished data Results Dose-intensity
Limiting toxicity syndromes (LTS): overall and in young-elderly patients Medical Oncology, S. Salvatore Hospital, University of L'Aquila, Preliminary unpublished data Results Toxicity
Limiting Toxicity Syndromes (LTS) Results Toxicity
Gastrointestinal toxicity in elderly patientsOutline • 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
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
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
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
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