A phase II study of paclitaxel, weekly, 24-hour continous infusion 5-fluorouracil, folinic acid and cisplatin in patients with advanced gastric cancer.

To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel, cisplatin and 24 h continuous infusion of 5-FU/folinic acid in patients (pts) with unresectable, locally advanced or metastatic gastric adenocarcinoma. Forty-five chemotherapy-naive pts (28 male and 17 female) with a median age of 60 years (range 35-74) were enrolled. 5-FU 2 g/m2 was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m2 as a 2 h infusion. Paclitaxel 175 mg/m2 was administered as a 3 h-infusion on days 1 and 22 and cisplatin 50 mg/m2 as 1 h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29, 36) followed by 2 weeks rest were considered one cycle. A median of 3 cycles (range 1-4) were administered to 45 pts assessable for response, survival and toxicity. Five pts (11%) obtained a CR and 18 pts (40%) a PR (ORR 51%; 95% CI: 35.8-66.3%). Responses were achieved in the liver, lymph nodes, lungs and at the site of the primary tumour. Nine pts (20%) had stable disease. Thirteen pts (29%) were considered to have failed treatment, 8 pts (18%) due to progressive disease and 5 pts (11%) who did not receive one complete cycle of therapy due to acute non-haematologic toxicity. The median progression-free and overall survival times were 9 months (range 1-36+) and 14 months (range 2-36+), respectively. Neutropenia WHO III(o)/IV(o) occurred in 7 pts (15%) with only 1 pt having grade IV. Additional non-haematologic WHO III(o)/IV(o) toxicities included nausea/vomiting in 5 (11%), alopecia in 22 (49%), and diarrhoea in 1 patient each (2%). Dose reductions or treatment delays were necessary in 8 pts (17%), mainly due to neutropenia. All pts were treated on an outpatient basis. The combination of paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of pts with advanced gastric cancer. While the overall acceptable toxicity allows its use in the palliative setting, it may also be an attractive option to be tested for neoadjuvant or adjuvant treatment.

Recovery of hypoglycaemia-associated compromised cerebral function after a short interval of euglycaemia in insulin-dependent diabetic patients.

To test the hypothesis that compromised cerebral function, induced by recurrent hypoglycaemic episodes, may recover after a short interval of euglycaemia, we examined electrophysiological activity and symptom awareness during two sequential euglycaemic-hypoglycaemic clamp studies in 11 insulin-dependent diabetic patients without any signs of peripheral or autonomic neuropathy. Neurophysiological testing and evaluation of hypoglycaemic symptoms were performed at stable glycaemic plateaus of 5.6, 3.3, 2.2, and 1.7 mmol/l. The first clamp study was preceded by 3 short-term hypoglycaemic episodes, whereas the second clamp study followed a 2 day interval of strict euglycaemia. The latter caused a recovery of electrophysiological activity, which was demonstrated by recovery of delays of the middle latency auditory evoked potentials (latency shift of the P(a) component, MANOVA, P < 0.01). Reversal of hypoglycaemic symptom unawareness involved the overall symptom perception (MANOVA, P < 0.04), as well as the autonomic symptoms of heart pounding (P < 0.05) and sweating (P < 0.05). We conclude that the previously reported impaired cerebral function, occurring as a consequence of repetitive hypoglycaemic episodes, may recover after a single euglycaemic interval.