P-0087 - Trastuzumab in Treatment of Her-2 Positive Advanced Gastric Cancer - Single Institution Experience

Abstract

Background: Most of the patients with gastric cancer have locally advanced or metastatic disease at the time of presentation. Her2 over-expression and/or amplification are present in 7-34% of gastric or gastroesophageal junction (GEJ) cancers. It has been demonstrated that trastuzumab (Herceptin®) in combination with fluoropyrimidine based chemotherapy is superior to chemotherapy alone in this group of patients. We hereby report our experience and safety evaluation of therapy with trastuzumab, in combination with chemotherapy in the treatment of patients with advanced gastric cancer. Methods: Data on eight consecutively treated patients with histologically confirmed gastric or GEJ adenocarcinoma, with Her2 over-expression and/or amplification (IHC 3 +, or IHC 2+ and SISH+) who received first line treatment with trastuzumab were analyzed retrospectively. The treatment consisted of cisplatin at dose of 80mg/m2 on day 1 and trastuzumab at doses of 8 mg/kg (loading dose on the first cycle) and 6 mg/kg (maintenance dose) on day 1 of subsequent cycles, followed by capecitabine 1000 mg/m2 twice daily for 14 days. Cycles were repeated on 21 days. Chemotherapy was given for maximum of 8 cycles and trastuzumab was continued until disease progression or unacceptable toxicity. LVEF assessments were done at baseline and every 3 months afterwards. Results: Eight patients (pts), 3 with locally advanced inoperable disease and 5 with metastatic disease were included. The median age was 62 years (range 40-67). Patients received an average of 5 cycles (range 2-14). The therapy is still ongoing in 5 pts. Partial disease remission was observed in 2 pts (25%) and another 3 (37.5%) had stabile disease. Disease progression was detected in 3 pts (37.5%). The most common adverse non cardiac events were grade 1 and 2; anemia and neutropenia in 5 pts (62.5%), thrombocytopenia and nausea in 3 pts (37.5%), mucositis, fatigue and anorexia in 1 (12.5%). Hand-foot syndrome grade 3 toxicity was reported in 1 case (12.5%) after the 7th cycle of therapy. No grade 4 hematologic toxicities were diagnosed. A minor cardiac adverse event consisting of 10% drop of LVEF to an absolute value within normal parameters was observed. Conclusion: Targeting human epidermal growth factor receptor 2 (HER2) during or in sequence with chemotherapy improves overall survival in metastatic and locally advanced inoperable HER2-overexpressing gastric or gastroesophageal junction cancer. Good tolerability, the low incidence of high grade toxic events encourages the use of Herceptin in combination with chemotherapy in treatment of HER-2 positive gastric carcinoma.