Background-In Japan, endoscopic mucosal resection (EMR) is accepted as a treatment option for cases of early gastric cancer (EGC) where the probability of lymph node metastasis is low. The results of EMR for EGC at the National Cancer Center Hospital, Tokyo, over a 11 year period are presented. Methods-EMR was applied to patients with early cancers up to 30 mm in diameter that were of a well or moderately histologically diVerentiated type, and were superficially elevated and/or depressed (types I, IIa, and IIc) but without ulceration or definite signs of submucosal invasion. The resected specimens were carefully examined by serial sections at 2 mm intervals, and if histopathology revealed submucosal invasion and/or vessel involvement or if the resection margin was not clear, surgery was recommended. Results-Four hundred and seventy nine cancers in 445 patients were treated by EMR from 1987 to 1998 but submucosal invasion was found on subsequent pathological examination in 74 tumours. Sixty nine percent of intramucosal cancers (278/ 405) were resected with a clear margin. Of 127 cancers without "complete resection", 14 underwent an additional operation and nine were treated endoscopically; the remainder had intensive follow up. Local recurrence in the stomach occurred in 17 lesions followed conservatively, in one lesion treated endoscopically, and in five lesions with complete resection. All tumours were diagnosed by follow up endoscopy and subsequently treated by surgery. There were no gastric cancer related deaths during a median follow up period of 38 months (3-120 months). Bleeding and perforation (5%) were two major complications of EMR but there were no treatment related deaths. Conclusion-In our experience, EMR allows us to perform less invasive treatment without sacrificing the possibility of cure. (Gut 2001;48:225-229)

No abstract

NK911 is a novel supramolecular nanocarrier designed for the enhanced delivery of doxorubicin (DXR) and is one of the successful polymer micelle systems to exhibit an efficient accumulation in solid tumours in mice. The purpose of this study was to define the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of NK911 and to evaluate its pharmacokinetic profile in man. NK911 was given intravenously to patients with solid tumours every 3 weeks using an infusion pump at a rate of 10 mg DXR equivalent min À1 . The starting dose was 6 mg DXR equivalent m À2 , and the dose was escalated according to the accelerated titration method. A total of 23 patients participated in this study. Neutropenia was the predominant haematological toxicity, and grade 3 or 4 neutropenia was observed at doses of 50 and 67 mg m À2 . Common nonhaematological toxicities were mild alopecia, stomatitis, and anorexia. In the dose identification part of the study, DLTs were observed at a dose of 67 mg m À2 (grade 4 neutropenia lasting more than 5 days). Thus, this dosage level was determined to be the MTD. Infusion-related reactions were not observed in any cases. The C 5 min and area under the concentration curve parameters of NK911 exhibited dose-dependent characteristics. Among the 23 patients, a partial response was obtained in one patient with metastatic pancreatic cancer. NK911 was well tolerated and produced only moderate nausea and vomiting at myelosuppressive dosages. The recommended phase II dose was determined to be 50 mg m À2 every 3 weeks.

Neither investigational regimen, FP nor UFTM, showed a survival advantage as compared with FU alone. FU alone will remain a reference arm in our future trial for advanced gastric cancer.

This study identified several UGT1A1 haplotypes significantly associated with the reduced AUC ratio (*28 and *6) and with the increased total bilirubin level (*28, *60, and *IB) and suggested that the novel haplotype *IB might be functionally important. These findings will be useful for further pharmacogenetic studies on adverse reactions to irinotecan.

The haplotypes significantly associated with reduced area under concentration curve ratios and neutropenia contained UGT1A1*6 or *28, and both of them should be genotyped before irinotecan is given to Japanese and probably other Asian patients.

A dose-escalation study of cisplatin (CDDP) combined with S-1, a new oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was given orally at 40 mg m À2 b.i.d. for 21 consecutive days following a 2-week rest. CDDP was planned to be given intravenously on day 8, at a dose of 60, 70, or 80 mg m À2 depending on the DLT. Treatment was repeated every 5 weeks, unless disease progression was observed. In the phase I portion, the MTD of CDDP was presumed to be 70 mg m À2 , because 33.3% of patients (2/6) developed DLTs, mainly neutropenia. Therefore, the RD of CDDP was estimated as 60 mg m À2. In the phase II portion, 19 patients including six patients of the RD phase I portion were evaluated. The median administered courses was four (range: 1 -8). The incidences of severe (grades 3 -4) haematological and nonhaematological toxicities were 15.8 and 26.3%, respectively, but all were manageable. The RR was 74% (14/19, 95% confidence interval: 54.9À90.6%), and the median survival day was 383. This regimen is considered to be active against AGC with acceptable toxicity.

This phase I study was designed to examine the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs), the recommended dose (RD) for phase II, and the pharmacokinetics of NK105, a new polymeric micelle carrier system for paclitaxel (PTX). NK105 was administered as a 1-h intravenous infusion every 3 weeks, without antiallergic premedication. The starting dose was 10 mg m À2 , and the dose was escalated according to the accelerated titration method. Nineteen patients were recruited. The tumour types treated included pancreatic (n ¼ 11), bile duct (n ¼ 5), gastric (n ¼ 2), and colonic (n ¼ 1) cancers. Neutropenia was the most common haematological toxicity. A grade 3 fever developed in one patient given 180 mg m À2 . No other grades 3 or 4 nonhaematological toxicities, including neuropathy, was observed during the entire study period. DLTs occurred in two patients given 180 mg m À2 (grade 4 neutropenia lasting for more than 5 days). Thus, this dose was designated as the MTD. Grade 2 hypersensitivity reactions developed in only one patient given 180 mg m À2 . A partial response was observed in one patient with pancreatic cancer. The maximum concentration (C max ) and area under the concentration (AUC) of NK105 were dose dependent. The plasma AUC of NK105 at 150 mg m À2 was approximately 15-fold higher than that of the conventional PTX formulation. NK105 was well tolerated, and the RD for the phase II study was determined to be 150 mg m À2 every 3 weeks. The results of this phase I study warrant further clinical evaluation.