13121 Purpose: To determine whether UGT1A1, UGT1A7, and UGT1A9 polymorphisms affect pharmacokinetics (PK) of irinotecan and treatment outcome of Korean patients with advanced non-small cell lung cancer (NSCLC). Methods: Eighty-one patients with advanced NSCLC were treated with irinotecan and cisplatin chemotherapy. Genomic DNA was extracted from peripheral blood and genotyped using direct sequencing. We analyzed the association of UGT1A genotypes with irinotecan PK and clinical outcomes. Results: In genotype-PK association analysis, UGT1A1*6/*6 (n = 6), UGT1A7*3/*3 (n = 6) and UGT1A9–118(dT)9/9 (n = 11) were associated with significantly lower AUCSN-38G/AUCSN-38 ratio (P = 0.002, 0.009and 0.001, respectively). In linkage disequilibrium (LD) analysis, the UGT1A7 variants were highly linked with UGT1A1*6 (D` = 0.85, r2 = 0.63) and UGT1A9*22 (D` = 0.95, r2 = 0.88), which was substantiated in haplotype analysis. Patients with UGT1A1*6/*6 had lower tumor response and higher incidence of severe neutropenia. UGT1A9–118(dT)9/9 also showed a trend for high incidence of severe diarrhea, but not tumor response. In survival analysis, patients with UGT1A1*6/*6 had significantly shorter progression-free survival (P = 0.001) and overall survival (P = 0.017). Conclusions: These findings suggest that UGT1A1*6 and UGT1A9*22 genotypes may be important for SN-38 glucuronidation and associated with irinotecan-related severe toxicity. Specifically, UGT1A1*6 might be useful for predicting tumor response and survival outcome of Korean patients with NSCLC treated with irinotecan-based chemotherapy. (Supported in part by NCC Grant 0210130 and 0510080 from National Cancer Center, Korea). No significant financial relationships to disclose.
4030 Background: The perioperative treatment strategy for locally advanced gastric cancer (LAGC) has not been clearly established. We conducted a randomized phase II study of neoadjuvant vs. adjuvant docetaxel/cisplatin (DC) chemotherapy in LAGC. Methods: LAGC was radiographically defined by CT and PET. Pts were randomized to receive neoadjuvant or adjuvant DC (docetaxel 36 mg/m2 + cisplatin 40 mg/m2 on D1, D8, q 3 wks X 3 cycles) according Japanese staging system (IIIa, IIIb, IV M-, and IV with a single M+ node). Results: All planned 88 pts in 44 per each arm were enrolled between Jan 2003 and Nov 2005. One pt was not eligible. The median age was 57 yrs vs. 58 yrs, PS 1 90.7% vs. 84.1%, and stage III/IV 72.1%/27.9% vs. 70.5%/29.5% in the neoadjuvant and adjuvant arm, respectively. Clinical response rate of 42 evaluable pts in neoadjuvant arm according to WHO criteria was 64.3% (95% CI 49.8–78.8%) with CR 2.4%, PR 61.9%, SD 31.0%, and PD 4.7%. There was no treatment related death. Comparison of G3/4 adverse events in neoadjuvant vs. adjuvant arm were; leukopenia 14.0% vs. 32.4% (p=0.04), neutropenia 37.2% vs. 62.2% (p=0.02), febrile neutropenia 0% vs. 2.7%, diarrhea 2.3% vs. 10.8%, stomatitis 2.3% vs. 8.1% (p=NS). There were no difference in the postoperative morbidity and the duration of hospital stay between both arms, but surgery was delayed in one pt who developed tuberculosis during neoadjuvant chemotherapy. Downstaging of the T stage could be obtained in 6 (14.3%) among 42 evaluable pts in neoadjuvant arm, according to EUS. Conclusions: Both neoadjuvant and adjuvant DC chemotherapy were relatively well tolerated in LAGC, with the lower incidence of G3/4 toxicities in neoadjuvant arm. Neoadjuvant DC showed a high response rate and a modest downstaging effect. (Supported by National Cancer Center Grant; Docetaxel was provided by Sanofi Aventis Korea) [Table: see text] No significant financial relationships to disclose.
modeling, particularly for treatments with non-coplanar geometries or largely off-centered isocenters. Acquired surfaces and the CT generated body contours showed good agreement. Conclusion: Efficacy of efficient full-body surface acquisition for patientspecific collision modeling have been demonstrated. With personalized modeling, the safety of radiotherapy delivery could be ensured while achieving the full dosimetric benefit of non-coplanar beam geometries.
Background: The biologic behavior of metaplastic breast cancer (MBC) has not been well elucidated due to its rarity and heterogeneity. This study was designed to assess the clinical and tumor characteristics and outcomes of MBC patients as compared with invasive ductal carcinoma (IDC) in general and the triple-negative (TN) subtype.Materials and methods: This study included 35 MBC and 2,839 IDC patients diagnosed at the National Cancer Center, Korea between 2000 and 2008. We, retrospectively, reviewed the clinicopathologic characteristics and clinical outcomes.Results: The mean age was 47.4 years for MBC group and 48.3 years for IDC group. The MBC group presented with larger tumors (≥ T2, 78.8% vs 41.0%; P<0.001), higher histologic grade (grade 3, 92.0% vs 44.6%; P<0.001), fewer ER and PgR positivity (ER+, 14.3% vs 69.0% ; P<0.001 and PgR+, 25.7% vs 66.1%; P<0.001), higher Ki-67 expression (35.5%±26.2% vs 20.6% ±19.8%; P=0.024) and more TN subtypes (48.6% vs 11.9%; P<0.001) than IDC group. Excluding de novo stage IV patients, 14 of 32 (43.7%) MBC patients and 260 of 2782 (9.4%) IDC patents developed disease recurrence with a median follow-up of 36.2 months (range, 4.9-117.8 months). MBC was a poor prognostic factor for disease recurrence in univariate and multivariate analysis (HR 5.19; 95% CI, 2.04-13.18; P=0.001). MBC patients demonstrated aggressive pathologic features and experienced more disease recurrence (HR 4.77; 95% CI, 1.99-11.44; P=0.001) even when compared with 330 patients with TN subtype.Conclusions:Patients with metaplastic breast carcinoma appeared to have inherent aggressive tumor biology with poorer clinical outcomes than those with IDC in general and TN subtype.Partly supported by NCC Grant No 0610240 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4057.
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