ABSTRACT
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.
Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/secondary , Antimetabolites, Antineoplastic/administration & dosage , Colorectal Neoplasms/pathology , Fluorouracil/administration & dosage , Leucovorin/administration & dosage , Adult , Aged , Antimetabolites, Antineoplastic/adverse effects , Antimetabolites, Antineoplastic/therapeutic use , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Female , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Humans , Infusions, Intravenous , Male , Middle Aged , Treatment OutcomeABSTRACT
The association between venous deep thrombosis and the presence in circle of antiphospholipid antibodies in a patient affection from LES has prompted the authors to any considerations on the physiopathology and the therapy of an identified syndrome recently, of big clinical interest and surely not frequent in the departments of inside medicine. The authors also review the literature on the subject.
Subject(s)
Antiphospholipid Syndrome , Adult , Ampicillin/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/therapy , Cephalosporins/therapeutic use , Cortisone/therapeutic use , Diagnosis, Differential , Fibrinolytic Agents/therapeutic use , Heparin/therapeutic use , Humans , Lupus Erythematosus, Systemic/diagnosis , Male , Penicillins/therapeutic use , Plasmapheresis , Thrombophlebitis/diagnosisABSTRACT
The association sarcoidosis-lung abscess due to emerging microorganisms-mycetoma has prompted the authors to report the above clinical case which is interesting in view of the rarity of the disease and of its infective complications. The authors also review the literature on the subject.
