Perioperative Cetuximab with Cisplatin and 5-Fluorouracil in Esogastric Adenocarcinoma: A Phase II Study.

PURPOSE: While perioperative chemotherapy provides a survival benefit over surgery alone in gastric and gastroesophageal junction (G/GEJ) adenocarcinomas, the results need to be improved. This study aimed to evaluate the efficacy and safety of perioperative cetuximab combined with 5-fluorouracil and cisplatin. PATIENTS AND METHODS: Patients received six cycles of cetuximab, cisplatin, and simplified LV5FU2 before and after surgery. The primary objective was a combined evaluation of the tumor objective response (TOR), assessed by computed tomography, and the absence of major toxicities resulting in discontinuation of neoadjuvant chemotherapy (NCT) (45% and 90%, respectively). RESULTS: From 2011 to 2013, 65 patients were enrolled. From 64 patients evaluable for the primary endpoint, 19 (29.7%) had a morphological TOR and 61 (95.3%) did not stop NCT prematurely due to major toxicity. Sixty patients (92.3%) underwent resection. Sixteen patients (/56 available, 28.5%) had histological responses (Mandard tumor regression grade ≤3). After a median follow-up of 44.5 months, median disease-free and overall survival were 24.4 [95% CI: 16.4-39.4] and 40.3 months [95% CI: 27.5-NA], respectively. CONCLUSION: Adding cetuximab to the NCT regimen in operable G/GEJ adenocarcinomas is safe, but did not show enough efficacy in the present study to meet the primary endpoint (NCT01360086).

Favorable prognosis of upper-gastrointestinal bleeding in 1041 older patients: results of a prospective multicenter study.

BACKGROUND & AIMS: Upper-gastrointestinal bleeding (UGIB) in the elderly is associated with high morbidity and mortality. The aims of this study were to determine the prognostic factors of UGIB in a large cohort of elders. METHODS: From March 2005 to February 2006, we conducted a prospective multicenter study in 53 French hospitals that consecutively enrolled 3287 patients for UGIB. A total of 1041 patients (47.8% women) were older than 74 years. Their epidemiologic characteristics and prognosis were compared with the 2246 younger patients (26.8% women). RESULTS: Elders more frequently took drugs causing UGIB: 65% versus 32% for younger patients (P < 10(-6)). Peptic ulcers, erosive gastritis, and esophagitis accounted for 63.6% of UGIB causes in elders versus 39.7% in younger patients (P < 10(-4)). Conversely, esogastric varices and gastropathy were responsible for 11% of UGIB in elders versus 44% in younger patients (P < 10(-6)). The rebleeding rate, morbidity, and in-hospital mortality were not statistically different between elders and younger patients: 11.8% versus 9.7% (P = .07), 22.6% versus 21.6% (P = .5), and 8.9% versus 8.2% (P = .5), respectively. Transfusion requirements, need for surgery, and length of stay were significantly different between elders and younger patients: 73% versus 57.5% (P < 10(-6)), 4% versus 2.5% (P < .02), 10.6 +/- 15.6 versus 8.5 +/- 12.4 days (P < 10(-6)), respectively. Whatever the etiology (peptic lesions or portal hypertension) in-hospital mortality was the same: 6.5% versus 7.3% and 10.9% versus 11.3%, respectively. CONCLUSIONS: Elders can do as well as younger patients with acute UGIB. Although the reasons are not completely clear, they may be related to differences in treatment.

High dose daily interferon-alpha induction and secondary adjunction of ribavirin in treatment-naive patients with chronic hepatitis C. A multicentric, randomised, controlled trial.

OBJECTIVES: To evaluate in naive patients with chronic hepatitis C 1- the efficacy and safety of one month interferon alpha (IFN-alpha) induction regimen; 2- the potential virological benefit of a secondary adjunction of ribavirin among HCV RNA negative patients after 20 weeks of IFN therapy, with or without an initial 4-week IFN induction. MATERIAL AND METHODS: 151 naive HCV-RNA positive patients presenting with biopsy- proven chronic hepatitis C and elevated ALT were randomised in a 2: 1 ratio in two arms: IFN-alpha 3 MU thrice a week (tiw) for 24 weeks (non-induced patients); IFN-alpha 6 MU daily for two weeks, then 3 MU daily for two weeks then 3 MU tiw for 20 weeks (induced patients). At week 24, HCV-RNA negative patients were randomised to receive in addition or not ribavirin 1-1.2 g daily for 24 additional weeks. Induction efficacy was assessed on the early viral response (EVR) defined as undetectable HCV RNA at week 4 then week 20. Ribavirin efficacy was assessed on the proportion of maintained complete response until the end of follow-up, 24 weeks after discontinuation of treatment. Data were analysed on an intent-to-treat basis. RESULTS: Efficacy of IFN-alpha induction: 104 patients were randomised to the non-induction group, 47 to the induction group. Gender, age, genotype distribution and HCV viral load at baseline did not differ significantly between the two groups. There was one treatment discontinuation because of adverse events in induced patients versus four in non-induced patients (P > 0.05). The 4 week EVR was significantly greater in induced patients in patients with HCV genotype 1, 4 or 5 (47% vs 12%, P=0.0002) only. There was no impact of induction in patients with HCV genotype 2 or 3. Efficacy of ribavirin: at week 24, 28 and 26 HCV-RNA negative patients were randomised to addition of ribavirin or not, respectively. Patients randomised to secondary additive ribavirin were more often HCV-RNA negative at the end of follow-up than patients treated with IFN-alpha alone: 18/28 (64%) vs 10/26 (39%); P=0.06. Among patients randomised to bitherapy, the relapse rate was significantly lower in patients with genotype 2 or 3 (0/12 vs 6/13, P=0.01) and not in those with genotype 1, 4 or 5 (5/11 vs 3/6, P=0.99). CONCLUSION: A 4 week IFN-alpha induction significantly increases the EVR rate in patients with HCV genotype 1, 4 or 5. Late secondary adjunction of ribavirin to IFN-alpha for 6 months in HCV-RNA negative patients after 6 months of IFN-alpha significantly decreases the relapse rate in patients with HCV genotype 2 or 3, but not in patients with genotypes 1, 4 or 5.