A phase I trial of 5-day chronomodulated infusion of 5-fluorouracil and 1-folinic acid in patients with metastatic colorectal cancer.

The aim of this phase I study was to establish the maximum tolerated dose (MTD) of 5-fluorouracil (5-FU), administered as a 5-day chronomodulated infusion in combination with 1-folinic acid (FA) to ambulatory metastatic colorectal cancer patients. Consecutive cohorts of 6 patients were given 5-FU and FA infusions from 10.00 p.m. to 10.00 a.m. with peak delivery at 4.00 a.m. by means of a multichannel programmable pump. The FA dose was always the same (150 mg/m2/d). For the first cohort, the 5-FU dose level was 600 mg/m2/d at the first course, escalated by 100 mg/m2 for each subsequent cohort. Intrapatient dose was also escalated by 100 mg/m2 if toxicity was less than grade 2. The courses were repeated every 3 weeks. Thirty-four patients (17 previously treated) received a total of 154 courses. Dose-limiting toxicity consisted of stomatitis and diarrhoea. No significant haematological, cutaneous or cardiac toxicity was encountered. The MTD of 5-FU was reached at the fourth level (first course at 900 mg/m2/d equal to 4500 mg/m2/course) with 5-FU increased to 1100 mg/m2/d (5500 mg/m2/course) in 4 patients. The received 5-FU dose intensity (DI) over the first 3 courses at this level was 1318 mg/m2/week. Thirty-three patients were assessed for response. An objective response was achieved in 1 out of the 13 previously-treated and in 8 out of the 20 previously-untreated patients. The chronomodulated infusion of 5-FU at a dose of 900 mg/m2/d, together with FA at 150 mg/m2/d for 5 days, was safely delivered to out-patients with metastatic colorectal cancer. The low toxic profile and activity of this regimen in previously untreated patients deserves further exploration for the treatment of 5-FU-sensitive tumours.

[Laparoscopic ultrasonography in laparoscopic surgery and diagnosis]. / Ecografia laparoscopica in chirurgia e diagnostica laparoscopica.

The authors report their experience with 101 patients examined with laparoscopic ultrasound (LU) using a dedicated 7.5-MHz linear probe which can be introduced through the 10-mm surgical trocars. In the patients undergoing laparoscopic cholecystectomy (77 cases), LU adequately demonstrated gallbladder wall and contents in all cases and visualized the main bile duct in 93.5% of cases; stones of the CBD or cystic duct were demonstrated in two cases. The liver was studied in 18 patients undergoing diagnostic laparoscopy or laparoscopic colonic resection: secondary lesions were identified in two cases, while benign lesions (cysts or angiomas) were seen in 6 cases. In the patients operated on for colonic resection (8 cases), LU was successfully used to localize the enteric tract affected by the tumor and to mark safety margins for excision. The technical features of the exam are reported and the main imaging findings discussed. The authors conclude that LU is a safe method which is easy to perform and does not significantly increase the operating time; the indications of this laparoscopic application of ultrasound are not yet defined but the application area will certainly widen in the future, as operative and diagnostic laparoscopy are more and more frequently used by surgeons.