(1)Faivre-Finn C, Bouvier AM, Mitry E et al. Chemotherapy for colon cancer in a well-defined French population: is it under- or over-prescribed?

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1 Colorectal cancer Chemotherapy for the elderly Dr Christophe TOURNIGAND Hôpital Saint Antoine France Hôpital Charles Lemoyne - Quebec GERCOR EPOG - UPMC

2 Colorectal cancer ( CRC) : an Elderly Disease 3rd leading cause of cancer death worldwide, More than 800, new cases are diagnosed annually, 40% of cases occur in patients >75 years of age

3 Colorectal cancer ( CRC) : an Improving Survival 5-years survival increases in 75yrs pts to (47.1% versus 53.6%, respectively; p <.001) Resection Post-operative operative mortality

4 CRC in Elderly : Undertreated! Côte d Or department ( ) 1998) (1) : % of patients treated with chemotherapy > 75 years < 65 years -Stade II CCR 4,9% 47,3% -Stade III CCR 24,4% 86,1% -Metastatic disease (2) (2) 8% 8% 44,1% (1)Faivre-Finn C, Bouvier AM, Mitry E et al. Chemotherapy for colon cancer in a well-defined French population: is it under- or over-prescribed? Aliment Pharmacol Ther 2002;16(3):

5 DFS probab bility Disease-free Survival in Stage III Patients: N1 & N2 FOLFOX4 443 N1 LV5FU2 443 N1 FOLFOX4 229 N2 LV5FU2 232 N2 HR: 0.76 HR: % 11.5% Data cut-off: January 16, 2005

6 Time from Relapse to Death: ITT ity Probabil FOLFOX4 n= 258 median 21 months LV5FU2 n=334 median 24 months Patients alive with relapse (%) FOLFOX4 69 (6.1) LV5FU2 88 (7.8) 0 Time from relapse to death (months) Exploratory analysis

7 CRC in Elderly : Undertreated! Relapse in colon cancer : 2-3 years Life expectancy : AGE Life Expectancy years +7-8 years +5-6 years Adjuvant Metastatic "To treat or not to treat? that is the question: Whether 'tis nobler in the mind to suffer The slings and arrows of outrageous fortune

8 Lewis, JCO 2003 CRC in Elderly : Underrepresentation! Underrepresentation in clinical trials : NCI data, 495 trials, pts, only 32% > 65yrs were it should be 61%

9 Metastatic colorectal cancer Irinotecan Median survival rates reported among elderly patients with colorectal cancer treated with irinotecan based regimens

10 FOLFOX4 in Elderly Patients with Colon Cancer Cn : AP Pooled ldanlsis Analysis Study Comparator Setting N regimen 1 MOSAIC 1 5-FU/LV Adjuvant 2246 N IFL 1 st Line 546 de Gramont 3 5-FU/LV 1 st Line 420 Rothenberg 4 5-FU/LV 2 nd Line 530 Total André et al, NEJM 2004; 2 Goldberg et al, JCO 2004; 3 de Gramont et al, JCO 2000; 4 Rothenberg et al, JCO 2003

11 Oxaliplatin-based chemotherapy: DFS - PFS <70 years 70 years

12 Adverse Events (Gr > 3) p = 0.04 Age < 70 Age > p = 0.37 p = 0.38 Age < 70 Age > 70 Rate, Grad e p = 0.08 p = Rate, Grad e p = 0.38 p = Neutropenia Thrombocytopenia Fatigue 0 Neurotoxicity Diarrhea Nausea/Vomiting 60 Day Mortailty

13 Conclusions Elderly patients benefit from FOLFOX4 treatment to a similar degree to younger patients Elderly patients experience slightly more but manageable toxicity it Age alone should not be a criteria to exclude elderly patients from FOLFOX4 chemotherapy Caution Selected elderly patients for clinical trials 2 of 4 trials limited eligibility to patients < 75 years

14 OPTIMOX 1 Study design R A N D O M I S A T I O N N FOLFOX4 until progression OS 20 m FOLFOX7 x 6 cy slv5fu2 x 12 cy FOLFOX7 x6 cy OS 21.6 m

15 Optimox 1 - Overall Survival Patients >75 years vs Patients 75 years 1.0 rtion Propo > 75 years 20.7 months years months p = 0,

16 Targeted agents Avastin Cetuximab Panitumumab

17 Tolerance of Avastin in patient age groups 1 All (n=1,953) % <65 years (n=1,057) years 75 years 80 years* % (n=533) % (n=363) % (n=161) % GI perforation Postoperative bleeding or WHCs Grade 3/4 bleeding ATEs New/worsening HTN 60-day mortality rate Multivariate analysis identified risk factors for ATEs, which included ECOG PS and prior history of ATEs 2 * 75 and 80 years overlap; therefore, the total number for all subgroups does not add up to 1,953 The denominators (i.e. number of patients undergoing surgery at post-baseline only) are 622, 399, 156, 67 and 26, respectively 1. Kozloff, et al. ASCO 2008; 2. Sugrue, et al. JCO 2007

18 1 Age years DREAM study (Phase III) mfolfox7 + bevacizumab X6 cycles Or 1 mxelox + bevacizumab x6 cycles Or 1 mlv5fu2 or capecitabine + bevacizumab 3 months FOLFIRI bevacizumab 6 months CR 2 or PR or SD R A N D O M I S A T I O N bevacizumab + erlotinib until PD bevacizumab until PD

19 Validation of a Scale predictive of chemotherapies toxicities in Elderly G OLD ( (ongoing) Cognitive functions 1. j p Dependance Comorbidities Renal function and nutritial status Depression and helper 1. Date du jour et nom de la ville de l Hôpital 2. Répétition de trois mots (cigare, fleur, porte ou citron, clé, ballon) et après quelques minutes 3. Aide pour : -téléphoner -prendre les médicaments -faire les courses - tenir ses comptes -préparer les repas - conduire ou utiliser les -entretenir la maison transports 4. Appui monopodal 5s 1. Hospitalisation ti dans l année précédente éd 6. Poly médications > 5 7. Clairance de la créatinine >30ml/mn 8. Albuminémie >30g/l 9. Vous sentez vous souvent triste ou déprimé? 10. Présence de l Entourage* *Aidant ou famille etastatic colorectal cancer, breast cancer, ovarian cancer

20 Test drugs, combinations i Young patients Elderly patients Need for specific trials for elderly patients

21 Acknowledgments: Dr Elisabeth Carola Hôpital Senlis, France Oncology department of Hôpital Charles LeMoyne, QC