Tough to treat tumors in elderly. how far can we go? Jean-Luc Raoul Institut Paoli-Calmettes Marseille France

Transcription

1 Tough to treat tumors in elderly Pancreatic cancer: how far can we go? Jean-Luc Raoul Institut Paoli-Calmettes Marseille France

2 Top 5 causes of cancer death / age Cancer Statistics in the USA 2008, CA Cancer J Clin 2008

3 It s always tough to treat pancreatic cancer! Lancet Oncol, 2007

4 Pancreatic cancer in elderly Epidemiology: Japan: 29% are > 80 yrs SEER: 34,555 US pts, 32% > 74 yrs 3yr OS = 5% Baine M et al. PLoSOne 2011

5 Pancreatic cancer in elderly Epidemiology: SEER: US pts, 32% > 74 yrs Diagnosis: Biopsy (liver, pancreas - EUSguided) = mandatory Other histologies (neuroendocrine)

6 Pancreatic cancer in elderly Epidemiology: SEER: US pts, 32% > 74 yrs Diagnosis: Biopsy (liver, pancreas) = mandatory Other histologies (neuroendocrine) Treatment: Localized tumor: Surgery Adjuvant post resection Locally advanced Metastatic

7 Surgery French Surgical series (AFC) 1325 patients operated on for adenocarcinoma of the pancreatic head 384 between y 74 older than 80 y 70 y > 70 y Mortality 3.7 % 4.4 % NS Morbidity 53 % 58 % NS Overall survival n 1 y 3 y yr % 42 % % 48 % % 34 % % 36 % > % 30 % by courtesy of Dr O Turrini

8 Surgery French Surgical series (AFC) 941 patients operated on for adenocarcinoma of the pancreatic head Series from the AFC OS post resection DFS post resection by courtesy of Dr O Turrini

9 Adjuvant post-resection (Observation vs. Gemcitabine) Median age: 62 (34 82 yrs) SAE: Gemcitabine 14.5% Observation 8.5% Oettle H, et al. JAMA 2010

10 Adjuvant post-resection (Gemcitabine vs. 5FU bolus) Median age: 63 (31 85 yrs) Toxicity Gr 3 / 4: 5FU: 14 % (mucitis, diarrhea) Gemcitabine: 7.5% (haematol) Reasonable option Neoptolemos JP, et al. JAMA 2010

11 Locally advanced No gold standard RTCT: widely used in the US Very old and poor quality trials Recent trial: 74 pts included / target = 316 Improvement in RR and OS (38 vs 36 pts) Much more toxicity NCCN: no gold standard Loehrer PJ, et al ASCO 2008

12 Locally advanced French phase III trial: locally advanced pancreatic cancer vs - RTCT (60 Gy+FU+CDDP) then Gem (n = 59) - Gemcitabine alone (n = 60) Overall Survival Progression Free Survival Median age: 61 yr (38-80) LAPC: gemcitabine Chauffert B, et al. Ann Oncol, 2008

13 Metastatic disease gold standard = gemcitabine Randomization: gemcitabine (n = 63) LA ou M+ vs Primary end-point = clinical benefit 5FU (600mg/m²/sem) (n = 63) Burris HA 3rd et al J Clin Oncol 1997

14 Gemcitabine based combinations Vaccaro V et al N Engl J Med 2011

15 Gemcitabine = gold standard + Targeted agent? ERLOTINIB 569 Pts: Gemcitabine (n = 284) vs Gem + Erlo (n = 285) Moore et al, J Clin Oncol 2007

16 Metastatic pancreatic adenocarcinoma: FOLFIRINOX 111mo 11.1 vs 68mo mo vs 3.3 mo Exclusion criteria > 75 years, PS >1 Conroy T et al N Engl J Med 2011

17 Pancreatic adenocarcinoma Gemcitabine: gold standard for Metastatic disease (> 75 y) Locally advanced disease Adjuvant post resection

18 Gemcitabine in elderly Gemcitabine: usually good safety profile Gemcitabine efficacy and safety, full dose, palliative setting < 70 yrs n = yrs n = 42 Efficacy: DCR 67% 60% NS TTP 119 d 104 d OS 240 d 220 d Safety: Dose Reduc 40% 62% 0.03 Interruption 1.7% 2.4% Gr3-4 SAE anemia 8.8% 14.3% 0.02 neutropenia 21.1% 30.9% febrile neutropenia 35% 3.5% 24% 2.4% toxic death 0% 0% Influence of KPS Selected (PS 0 1) elderly l patients t undergoing gemcitabine do as well than younger patients Marechal R, et al. Pancreas 2008

19 Gemcitabine in elderly Japan, 36 patients > 65 yrs (median = 74 yrs) Gemcitabine mg/m² (D1-8-15, 15 / 4 wks) Gr 3 4 toxicities: Hematological: 22% Anorexia: 14% Interstitial pneumonia 3% SAE gr 3-4: in 32% if < 80 and 50% if > 80 y

20 Pancreatic cancer: How far can we go? In conclusion Pancreatic adenocarcinoma frequent > 70 y Surgical resection: If no contra-indication, ti Outcome similar to younger patients. Palliative: locally advanced or metastatic Gold standard = gemcitabine, Gemcitabine = well tolerated, Initially full dose?

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