Phase III trial comparing initial chemoradiotherapy (intermittent cisplatin and infusional 5-FU) followed by gemcitabine vs gemcitabine alone in patients with locally advanced non metastatic pancreatic cancer. Preliminary results.

International audienceBackground: The GITSG studies have shown a greater survival after 5 FU-based chemoradiotherapy (CHRT) than radiotherapy or polychemotherapy alone in patients (pts) with locally advanced non metastatic pancreatic cancer. This randomized trial evaluated whether initial CHRT adds to modern gemcitabine in term of Overall Survival (OS). Methods: Pts with WHO status 0-2, proven adenocarcinoma of the pancreas, without metastasis at CT-scan, and deemed non resectable, were randomized 1:1 between CHRT ( 60 Gy in 6 weeks, 2 Gy/fraction, concomitant with 5-FU, 300 mg/m2/24 h as a continuous infusion, day 1-5 every week and cisplatin, 20 mg/m2/d, day 1-5 at week 1 and 5) or gemcitabine (G) (1000 mg/m2 weekly 7q8w) as induction treatment. Maintenance treatment was G (1000 mg/ m2 weekly 3q4w) in both arms until progression or limiting toxicity. Stratification criteria were: center, WHO status and initial surgery. It was required to include 176 pts to detect an expected change in median OS from 6 to 12 months (bilateral α = 1% and β = 10%). Intent to treat survival analysis used the Logrank test. Results: Between 03/00 and 07/05, 59 pts were randomized to CHRT and 60 to G. Median follow-up at the 05/05 was 16 months. Pt characteristics were well balanced (CHRT/G) with mean age (60.1/62.7 year), sex ratio (1/ 1.4) and WHO status ( 0-1: 88%/73%, 2: 9%/23%). During the induction phase, more than 75% of the planned dose was completed in 81.4% of pts for radiotherapy, 52.5% for 5-FU and 50.8% for cisplatin and 76.7% of pts in the G arm. In CHRT and G arms, OS at 6 and 12 months were respectively 78/82% and 24/51%, with a median survival of 8.4/14.3 months (stratified log-rank p = 0.014). CHRT or G related toxicities during induction phase were grade 3/4 leukopenia (17%/10%), thrombopenia (8.5%/0%), non-haematological toxicity (37%/ 17%) with diarrhea (7%/0% ), cutaneous toxicity (0%/3%). One treatment-related death was observed in the CHRT arm (aplasia). Conclusion: Study was stopped before the planned inclusion due to lower survival with initial CHRT when compared to G alone. Reasons explaining this difference are under investigation

Multicentre randomised phase III trial comparing Tamoxifen alone or with Transarterial Lipiodol Chemoembolisation for unresectable hepatocellular carcinoma in cirrhotic patients (Fédération Francophone de Cancérologie Digestive 9402)

International audienceThe FFCD 9402 multicentre phase III trial was designed to compare the effects of the combination of Transarterial Lipiodol Chemoembolisation (TACE) and tamoxifen with tamoxifen alone on overall survival and quality of life in the palliative treatment of hepatocellular carcinoma with cirrhosis. From 1995 to 2002, 138 patients were randomised between the two groups. One hundred and twenty three patients were eligible including 61 in the Tamoxifen group and 62 in the TACE group. Baseline characteristics were similar: Child-Pugh class A: 70%, alcoholic cirrhosis: 76%, Okuda stage I: 71%, multinodular tumour: 70% and segmental portal vein thrombosis: 10%. At 2 years, the overall survival was 22% and 25% in the Tamoxifen and TACE groups (P = .68), respectively. Multivariate analysis identified four independent prognostic factors for survival: α-fetoprotein (AFP) &gt; 400 ng/mL (P = .008), abdominal pain (P = .011), hepatomegaly (P = .023) and Child-Pugh score (P = .032). The Spitzer Index level assessing the quality of life during follow-up did not differ between the two groups (P = .70). Amongst patients with stage Okuda I, the 2-year overall survival was 28% in the Tamoxifen group and 32% in the TACE group (P = .58). In this subgroup, two prognostic factors were statistically significant for survival: AFP &gt; 400 ng/mL (P = .004) and Spitzer Index (P = .013) as shown by multivariable analysis.In conclusion, this study suggests that TACE improves neither the survival nor the quality of life in patients with HCC and cirrhosis.</p