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e13517 Background: Amrubicin (AMR) is a potent topoisomerase II inhibitor, and a promising agent for both small cell and non-small cell lung cancer. AMR is usually administered on days 1–3 intravenously. However, it causes severe, occasionally fatal, toxicity of leucopenia and neutropenia. The purpose of this study was to evaluate the safety and tolerability of AMR, to determine the recommended weekly dose, and to conduct a PK/PD study in patients with chemotherapy-refractory or recurrent lung cancer. Methods: Refractory or relapsed non-small cell and small cell lung cancer patients after 1 or 2 regimens, younger than 80 and with adequate main organ functions were eligible. AMR was initiated 45 mg/m2 given weekly (on day 1 and 8 q3wks). The dose level was increased by 5 mg/m2 by modified Fibonacci dose escalation scheme. Dose limiting toxicity (DLT) was assessed on the 1st cycle. Results: 16 patients were enrolled. Patients were 7 small cell lung cancer and 9 non-small cell lung cancer. 54 cycles (median: 3, range: 1–6) were administered in 5 dose levels. In 65 mg/m2 level, 3 patients had DLTs. The maximum tolerated dose was 65 mg/m2. The recommended weekly AMR dose was determined to be 60 mg/m2. Leucocytopenia, neutropenia, thrombocytopenia, and the dose level were correlated (p [Table: see text] [Table: see text]

19056 Background: TS-1 (S-1), a novel oral fluoropyrimidine derivative, is active against advanced non-small cell lung cancer (NSCLC). A response rate of 22% was reported in a monotherapy trial (Br J Cancer 2001). In combination with cisplatin, TS-1 demonstrated a response rate of 47% in NSCLC (Clin Cancer Res 2004). To develop a clinically relevant combination, we investigated TS-1 plus carboplatin in patients (pts) with advanced NSCLC in a phase I/II setting. Methods: Chemo-naive pts in stages IIIB and IV were enrolled with ages under 75, PS (ECOG) of 0 or 1, and with adequate bone marrow and major organ functions. Post-surgical relapses and asymptomatic brain metastases were allowed. In the phase I part, the doses of TS-1 were increased 60, 70, 80 mg/m2 orally from day 1 to 14, with the fixed dose of CBDCA (AUC=6 mg/mL min) on day 1. This regimen was repeated every 3 weeks. The phase II study was followed to evaluate response rate as the primary endpoint. Results: In the phase I part, the recommended d...

18007 Background: COX-2 overexpression is seen in many malignancies including lung cancer. Recent pre-clinical studies have shown that selective COX-2 inhibitors have demonstrated promising results when used with chemotherapy. Based on these observations, we are assessing the efficacy and tolerability of the combination chemotherapy consisting of C and P with meloxicam, a selective COX-2 inhibitor. Methods: Patients with stage IIIB or IV, ECOG PS 0 or 1, who had adequate organ function, were eligible. Patients received P 70 mg/m2 weekly for 3 of 4 weeks with C (AUC 6) on day 1, as well as daily meloxicam (10 mg/day). Response rate was the primary endpoint. Secondary endpoints were overall survival, toxicity profile and QOL (Using EORTC QLQ-C30 and LC13). Results: From March 2005 until September 2006, forty-four patients were evaluated in this study. Gender M/F; 31/13, median age; 64 yr (range, 34–75), stage IIIB/IV; 11/33, PS0/1; 22/22, histology Ad/Sq/Others; 29/6/9. Partial response was observed in 19 patients (43%), and no complete response, yielding an overall response rate of 43% (95% confidence interval, 28.5%-57.8%). Nineteen patients (43%) had stable disease. Seven patients (16%) had grade (G) 3 and three (7%) had G4 neutropenia. Three patients (7%) had G3 thrombocytopenia. As for non-hematological toxicities, one G4 toxicity (perforation of jejunum) was observed, but the other toxicities were mild (one muscle pain, 2 liver dysfunction, 1 fatigue and 1 nausea G3). Grade 2 peripheral neuropathy was observed in only one patient. Using EORTC QLO questioner, the global health status did not changed significantly during this therapy (before and 4 and 8 weeks later). Median follow-up was 9.6 months (range, 1.8–22.7 months). At the time of the final analysis (January 2007), 16 patients had died. The one-year survival rate was 70% and MST was not reached till now. Conclusions: Meloxicam in combination with C and weekly P chemotherapy showed promising activity with encouraging survival. This therapy is relatively well-tolerated in advanced NSCLC. No significant financial relationships to disclose.

13096 Background: Irinotecan is subject to substantial interindividual variability in pharmacokinetic and the occurrence of unpredictably severe toxicities of leukopenia or diarrhea. These toxicities have been reported to be associated with increased levels of SN-38, the active metabolite of irinotecan. ABCC2 and ABCG2, members of adenosine triphosphate-binding cassette transporters, are involved in mediating the elimination of anionic antitumor drugs, such as SN-38 and SN-38G. Recently, Innocenti et al. reported SN-38G AUC and SN-38G/SN-38 AUC ratios were correlated with ABCC2 3972T>C. The variant ABCG2 421C>A was associated with low ABCG2 expression levels and altered sensitivity to several drugs, including SN-38, in vitro as compared with the reference-type protein. Methods: We assessed whether the variants ABCC2 3972T>C and ABCG2 421C>A would be associated with severe toxicity (leucopenia of grade 4 and/or diarrhea of grade 3 or worse) in 120 Japanese cancer patients in which 27 patients experienced severe toxicity. Results: 74 patients (62%) were homozygotes for the reference allele of ABCC2 3972T>C, 39 heterozygous (33%), and 7 homozygous (6%) for the variant, whereas 62 patients (52%) were homozygous for the reference allele of ABCG2 421C>A, 48 heterozygous (40%) and 10 homozygous (8%) for the variant. Logistic regression analysis did not show any significant associations between the occurrence of severe toxicity and carrying these variants (see Table ). Conclusions: It suggests that genotyping of ABCC2 3972T>C and ABCG2 421C>A would not be useful for predicting severe toxicity caused by irinotecan. [Table: see text] No significant financial relationships to disclose.

7082 Background: Gefitinib has shown modest activity in pts with recurrent NSCLC after platinum-based chemotherapy. However, the activity of gefitinib as first-line chemotherapy remains unknown. We...

7312 Background: Constitutive overexpression of COX-2 is common in NSCLC, and this could be linked to tumor progression. Some preclinical studies suggest that a selective COX-2 inhibitor may augmen...

7174 Background: Concurrent chemoradiation has been proposed as one of the best treatments for locally advanced NSCLC. However, the optimal therapy for locally advanced NSCLC continues to evolve. T...

2009 Background: Irinotecan unexpectedly causes severe, occasionally fatal, toxicity of leukopenia or diarrhea. Irinotecan is metabolized by carboxylesterase to form an active SN-38, which is furth...