P-0042 Preliminary Safety Analysis From PAC-C Study of Capecitabine+Paclitaxel→Capecitabine Maintenance (PX-X) vs Capecitabine+Cisplatin (XP) As First-Line Chemotherapy for Recurrent/Metastatic Gastric Cancer

Abstract

IntroductionPAC-C is a randomized, multicenter, phase III study comparing the efficacy and safety of PX-X vs the standard XP regimen as first-line therapy for advanced gastric cancer (AGC). Here we report the findings from a protocol-specified preliminary safety analysis. MethodsPatients with previously untreated AGC, evaluable lesion(s) by RECIST 1.0, and KPS≥70 are eligible. All eligible patients are randomized to receive either PX-X or XP. Patients in the PX-X arm receive paclitaxel (80 mg/m2 3-hour infusion on days 1&8) and capecitabine (1000 mg/m2 twice daily on days 1–14) every 3 weeks for a maximum of 4 cycles; subsequently, patients with no disease progression receive maintenance capecitabine monotherapy (same dose/schedule) until progression or intolerable toxicity. Patients in the XP arm receive cisplatin (80 mg/m2 2-hour infusion on day 1) and capecitabine (same dose/schedule as in PX-X arm) for a maximum of 6 cycles. Adverse events (AEs) are evaluated according to CTC-AE (version 3.0). Study drug exposure, AEs and serious AEs (SAEs) were evaluated. The study is registered with ClinicalTrials.gov ID of NCT01015339. ResultsThe study started in November 2009 and is anticipated to finish recruitment by the end of May 2012. Up to 30 June 2011, 160 patients were recruited (81 patients in the PX-X arm and 79 patients in the XP arm). The safety analysis population includes 147 patients (79 in the PX-X arm and 68 in the XP arm). Baseline patient and disease characteristics (median age, gender ratio, and performance status) were similar in the treatment arms. The median number of treatment cycles was 4.0 in each arm (range 1–22 cycles in the PX-X arm and 1–8 cycles in the XP arm). Dose adjustments of platinum or paclitaxel were lower in the PX-X arm (11.4% for paclitaxel) than the XP arm (30.9% for cisplatin); dose adjustments of capecitabine were also lower in the PX-X arm (6.3% vs 22.1% in the XP arm). AEs resulting in dose adjustment or administration delay were lower in the PX-X arm (10.1% vs 19.1%). Gastrointestinal AEs (all grades) were reported in 20.3% of PX-X and 32.4% of XP-treated patients. Grade 3/4 AEs in the PX-X vs XP arms were as follows: gastrointestinal (2.5% vs 5.9%); leukocytopenia (13.9% vs 13.2%); anemia (0% vs 7.4%). SAEs (6.3% vs 4.4%) and treatment-related deaths (1.2% vs 0%) were similar in the two treatment arms. ConclusionThis preliminary analysis in 160 patients raises no safety concerns. The current findings suggest that treatment with PX-X is associated with fewer dose adjustments or treatment delays and a lower rate of gastrointestinal AEs than standard treatment with XP. The study is currently nearing completion of accrual.