4634 Background: S-1 is an oral prodrug of 5-fluorouracil (5-FU) including two modulators to enhance the antitumor effect and to decrease gastrointestinal toxicity. Paclitaxel has the synergistic antitumor effect with 5-FU. This study were planned to evaluate the efficacy and safety of S-1 and paclitaxel combination therapy in advanced gastric cancer. Methods: Eligible patients had untreated advanced or relapsed gastric cancer with measurable lesion(s), histologic proof, ECOG PS 0–2, adequate organ function, and signed informed consent. Treatment consisted of S-1 35mg/m2 p.o. b.i.d. on days 1–14 plus paclitaxel 70mg/m2 i.v. on days 1& 8 of a 21-day cycle. Measurable and/or unmeasurable lesion was assessed after every 2 courses with RECIST criteria. Results: A total of 56 patients (M/F=37/19) were enrolled. The median age was 59 years with advanced (n=43) and relapsed (n=13) gastric cancer. The common metastatic lesions were abdominal lymph nodes (71%), liver (39%), and peritoneum (21%). Out of 53 evaluable patients, there was 1 (2%) CR, 25 (47%) PRs, 21 (40%) SDs, and 6 (11%) PDs. Objective tumor response was 49%. Median duration of response was 5.4+months after the confirmation of response. Median follow-up was 9.6 month. Median PFS was 7.7 months and median survival was 14.6 months. Median number of cycle was 6 (range, 1–14). The relative dose intensity of S-1 and paclitaxel was 93%, both. The most common causes of delayed cycle and dose reduction were neutropenia and diarrhea, respectively. All 56 patients were assessed for safety. This treatment was well tolerated with grade 3/4 neutropenia in 14%/5%, grade 3 febrile neutropenia in 5%, grade 2/3 N/V in 21%/0%, anorexia in 18%/2%, diarrhea in 9%/4%, stomatitis in 7%/4%, and neuropathy 7%/0% of patients. Conclusions: S-1 and paclitaxel combination chemotherapy showed significant antitumor effect with manageable and tolerable toxicities in patients with advanced gastric cancer. (This study was partially supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (0412-CR01–0704–0001)) No significant financial relationships to disclose.

Background: Complete or partial loss of chromosome 7 is a recurrent chromosomal aberration frequently found in myeloid disorders such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). This finding is an important prognostic indicator associated with poor response to the treatment and faster disease progression. Aims: (1) to determine the breakpoints on the long and short arm of chromosome 7 using FISH with locus-specific probes; (2) to specify the frequency of these rearrangement; and (3) to evaluate overall survival [OS] of patients with chromosome 7 alteration. Methods: Diagnostic bone-marrow samples of 46 adults with AML/ MDS and with chromosome 7 aberration were examined. Karyotypes were analyzed using conventional and molecular cytogenetic techniques: FISH (Abbott, Kreatech), mFISH/mBAND (MetaSystems) and array CGH/SNP (Illumina, Agilent). Results: Monosomy 7 as a sole chromosomal abnormality was found in seven patients. Isolated deletion 7q was proved in one case only. In 38 cases, chromosome 7 aberrations were detected in combination with other changes (n = 16) or as a part of complex karyotype (n = 22). The most frequently altered regions on the long arm were identified in bands 7q22, 7q31 and 7q33-7q36. In 17 patients (37%), deletion of the EZH2 tumor suppressor gene located in band 7q36.1 was found. The most frequently altered regions on the short arm were identified in bands 7p11-p12. Rearrangements of 7p were always associated with other chromosomal alterations, the isolated 7p aberration was not proved. In 14 patients (30%), structural aberrations of both short and long arm 7p/7q were detected. In two cases, acquisition of additional clonal aberrations was observed during the disease. OS of the whole group was 6.45 months. Summary/Conclusion: In our cohort, the rearrangement of 7p as a sole aberration was not observed. A large heterogeneity of breakpoints was confirmed on the long arm 7q. High instability of chromosome 7 together with other chromosomal changes represent a marker of poor prognosis and is associated with rapid disease progression. In patients with myeloid malignancies, early detection of 7p/7q aberrations is important to precise prognostication and treatment decision.