Observational Study of Perioperative Chemotherapy in Gastric Cancer

Grupo Oncologico Cooperativo Chileno de Investigation61 enrolled

Overview

This study will assess the efficacy and toxicity of perioperative chemotherapy with Epirubicin + Cisplatin + Capecitabine (ECX) in routine clinical practice in a network of public hospitals in Santiago, Chile.

Chile belongs to the countries with a high mortality rate due to gastric cancer, and this disease is the most frequent cause of cancer death in Chile. Despite of adequate surgery, survival rates are disappointing, with less than 60% of patients for all stages achieving to be alive at 5 years. This is due to the fact that frequently gastric cancer is diagnosed at an advanced stage. For locally advanced gastric cancer a multimodality treatment is recommended, with the alternatives of surgery followed by chemotherapy (asian approach), surgery followed by chemoradiation (US approach) and perioperative chemotherapy (european approach). These three strategies are valid standard treatment options and have shown to improve overall survival in stage IB to IVA gastric cancer. Perioperative chemotherapy administered pre- and postoperatively, has shown to downstage the tumor, increase curative resection, progression free and overall survival. For patients with potentially resectable gastric cancer staged T2 or higher or cN+, NCCN Guidelines recommend perioperative chemotherapy (category1). Chilean guidelines for gastric cancer state the alternative of perioperative chemotherapy, however this approach has not been used widely in public hospitals because lack of financial support. Some gastric cancers overexpress HER2, and this subset of patients benefit from targeted therapy at an advanced stage. The proportions of patients with these molecular characteristics vary widely depending of the geographic area. The chilean population has been investigated in small series, but the incidence of HER2 positive gastric cancer is not known. We therefore plan to measure HER2 expression in all participating patients.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Gastric Cancer

Interventions

epirubicin + cisplatin + capecitabine polychemotherapyDRUG

EPIRUBICIN (LKM)at a dose of 50 mg/m2 over 15 minutes is administered every 21 days. CISPLATIN (LKM) at a dose of 60 mg/m2 over 4 hours is administered every 21 days. Patients must receive standardized hydration per protocol. CAPECITABINE (Xeloda®) at a dose of 625 mg/m2 BID (i.e. 1250 mg/m2/day) 30 minutes after meals from day 1 to day 21 of every cycle of chemotherapy. Antiemetic therapy: * Dexamethasone 8 mg IV and Ondansetron (LKM) 8 mg IV o Granisetron (Kytril®) prior to chemotherapy * Rescue Ondansetron (LKM) 8 mg IV will be given during 24-hour hospitalization in case of emesis * Symptomatic antiemetic therapy with thiethylperazine will be prescribed. Loperamide will be prescribed in case of diarrhea.

Eligibility

Sex: ALLMin age: 19 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically proven invasive carcinoma * Age \> 18 years. * ECOG performance status 0 or 1. * Hemoglobin \> 9 g/dL * Absolute neutrophil count \> 1.5 x 109/L * Platelet count \> 100 x 109/L * Creatinine \< 1.5 ULN * Creatinine clearance \> 60 mL/min * Serum bilirubin \< 1.5 x ULN * AST \< 2.5 x ULN * Women of child bearing potential: must agree to use an effective contraceptive method. * Signed informed consent. Exclusion Criteria: * ECOG \> 2. * Pre-existing diarrhea uncontrolled with supportive care. * Inability to swallow Xeloda tablets. * History of mild-to-moderate renal insufficiency (creatinine clearance \< 45 mL/min). * Signs or symptoms of clinically significant hepatic dysfunction (bilirubin \> 1.5 ULN, FA \> 2.5 ULN, albumin \< 2,5 g/dL). * Significant cardiac dysfunction (LVEF \< LLN) * Presence of distant metastasis, including clinical signs of peritoneal carcinomatosis * Symptomatic gastric retention or severe dysphagia with a caloric intake of \< 1500 kcal/day * Histology of lymphoma, GIST or neuroendocrine tumor * Pregnant or breast-feeding women. Female patients must be postmenopausal, surgically sterile or they must agree to use an effective method of contraception. * Any medical conditions that, in the investigator's opinion, would impose excessive risk to the patient. Examples of such conditions include congestive heart failure of Class III or IV of the NYHA classification, infection requiring parental or oral treatment, any altered mental status or any psychiatric condition that would interfere with the understanding of the informed consent.

Locations (1)

Instituto Nacional del Cáncer

Santiago, RM, Chile

Outcomes

Primary Outcomes

Rate of downstaging

To determine the rate of downstaging of locally advanced cT3-4 and/or N+ gastric carcinomas after 3 cycles of preoperative chemotherapy with ECX

Time frame: through study completion, an average of 3 months

Secondary Outcomes

Rate of adverse events

Rate and description of adverse events

Time frame: through study completion, an average of 6 months

Clinical response after three cycles of preoperative ECX

Clinical response based on RECIST criteria

Time frame: through study completion, an average of 6 months

To evaluate the surgical morbidity after three cycles of preoperative CT

Hospital stay duration

Time frame: through study completion, an average of 1 year

To evaluate the surgical mortality after three cycles of preoperative CT

30 days postoperative mortality rate

Time frame: through study completion, an average of 1 year

progression free survival

To evaluate the 3 year progression free survival

Time frame: through study completion, an average of 2 years

overall survival

To evaluate the 5 year overall survival (OS) of patients treated with perioperative CT

Time frame: through study completion, an average of 3 years

compliance with the planned postoperative therapy

Data from ClinicalTrials.gov

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