Prevention of 5-fluorouracil-induced early severe toxicity by pre-therapeutic dihydropyrimidine dehydrogenase deficiency screening: Assessment of a multiparametric approach.

5-Fluorouracil (5-FU)-based treatments can lead to early-onset severe (4%-5%) even fatal (0.3%) toxicities in patients with dihydropyrimidine dehydrogenase (DPD) deficiency. This multicenter prospective cohort study aimed to assess the clinical benefit of pretherapeutic screening for DPD deficiency using a multiparametric approach. Two parallel cohorts of patients treated with 5-FU-based chemotherapy for colorectal carcinoma were compared in a prospective nonrandomized study. In arm A, patients had DPD deficiency screening before treatment, whereas in arm B no pretherapy screening was performed. Dosing was based on 5-FU administration guidelines of each institution. DPD deficiency screening was performed using a combined multiparametric approach (5-FUODPM Tox). The frequency of early grade 4-5 toxic events potentially induced by 5-FU was compared in the two groups. At total of 1,142 patients (n = 1,116 evaluable) were enrolled. In arm A, out of 718 evaluable patients, nine grade 4 early toxicities potentially related to 5-FU were reported in nine patients (1.2%) with no toxic death despite one complete DPD deficiency and 24 partial deficiencies. The 24 patients with partial deficiency had safe pharmacokinetics (PK)-monitored 5-FU. In arm B, among 398 evaluable patients, 17 grade 4-5 toxic early events potentially related to 5-FU were reported in 12 patients (4.2%). The incidence of early severe toxicity was significantly higher in arm B (P = .0019), confirming the positive impact of pretherapeutic DPD assessment. The percent of patients with a toxicity grade 3 or higher observed in arm A was 10.8% (n = 78) compared to 17.55% (n = 69)  in arm B (P = .0497). The percentage of death was reduced from 2.5/1,000 in arm B to 0 in arm A. The time to occurrence of all grade ≥3 toxicities was determined in both arms and the difference between the two arms was significant (P = .047). Overall, one patient with complete DPD deficiency confirmed retrospectively died within 13 days from grade 5 multivisceral toxicity. Enrollment was prematurely closed after external experts' decision. In conclusion, multiparametric pretherapeutic DPD deficiency screening significantly lowered the risk of early severe toxicity and avoided an early toxic death. This approach should be used for safe administration of 5-FU-based treatments.

[Radiofrequency ablation of hepatocellular carcinoma in patients with cirrhosis]. / Traitement par radiofréquence des carcinomes hépatocellulaires sur cirrhose.

UNLABELLED: Radiofrequency is an effective therapeutic modality for patients with hepatocellular carcinoma. However few data are available with regard to the complication rate, the feasibility and long term survival. AIMS: To assess the response rate and complications of radiofrequency in cirrhotic patients with hepatocellular carcinoma. PATIENTS AND METHODS: Eighteen patients were enrolled. Each nodule was treated subcutaneously. Treatment response was assessed by computed tomography performed at 24 hours in 10 patients and every 3 months in all patients. Necrosis of the tumor was considered complete when hypodensity without enhanced contrast. RESULTS: Thirty hepatocellular carcinoma nodules with a mean tumor size of 30 mm; 15<30 mm and 15 >=30 mm, were treated by 1.3 radiofrequency sessions. Complete necrosis was achieved in 89%, greater for nodules<30 mm (100%) than for nodules >=30mm (80%). After a median follow up of 10.6 months, survival rate was 50%. Death was related to tumor involvement in 28%, to cirrhosis complications in 17% and to non liver-related disease in 5%. Three major treatment-related complications occurred (10%): subcapsular hematoma, sustained severe pain and peritoneal dissemination. All three complications were related to subcapsular location. CONCLUSION: Radiofrequency may be considered as an alternative treatment to percutaneous ethanol injection for hepatocellular carcinoma; however, subcapsular location has to be excluded when considering the observed morbidity. Prospective studies are warranted to evaluate the efficacy and morbidity of this treatment in hepatocellular carcinoma.