Combination of CPT-11 and LoHP vs Combination of 5-FU, Leucovorin and LoHP as 1st Line Treatment in Gastric Patients

A Randomized Phase II Study of Irinotecan and Oxaliplatin Versus the Combination of 5-FU/LV and Oxaliplatin, as First-Line Treatment in Patients With Locally Advanced or Metastatic Gastric Cancer

This phase II trial will compare the efficacy and toxicity of the combination of Irinotecan and Oxaliplatin versus 5-FU/LV and Oxaliplatin as first line treatment in patients with locally advanced or metastatic gastric cancer

There is no regimen considered standard in advanced gastric cancer. The reported response rates of 5-FU-based combination chemotherapy are higher than single agents (10-50%) but more toxic. The combination of 5-FU/LV and LOHP has demonstrated an ORR of 43%, median TTP of approximately 6,5 months and OS of 8,6 months in phase II trials, with an acceptable toxicity.

Irinotecan (CPT-11) is effective as salvage treatment in metastatic gastric cancer and has a synergistic activity with LOHP in preclinical trials

Inclusion Criteria:

• Histologically confirmed locally advanced or metastatic gastric cancer.
• Measurable or evaluable disease.
• Measurable disease is defined as at least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or 1 bidimensionally measurable lesion ≥ 20 X 10 mm. Lesions that are smaller or uni- or bidimensionally unmeasurable are considered as evaluable disease.
• Previous adjuvant chemotherapy with Irinotecan, Oxaliplatin and/or 5-FU based regimen. Patients who relapse within the first 6 months after the completion of adjuvant treatment are not eligible for the study.
• Karnofsky performance status > 70%.
• Age ≥18 years.
• Adequate liver (Bilirubin ≤ 1.5 UNL, SGOT/SGPT ≤ 4 UNL, ALP ≤ 2.5 UNL), renal (Creatinine ≤ 1.5 UNL) and bone marrow (ANC ≥ 1,500/mm3, PLT ≥ 100,000/mm3) function.
• Patients must be able to understand the nature of this study and give written informed consent.

Exclusion Criteria:

• Active infection
• History of serious cardiac disease (unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, ventricular arrhythmias)
• Previous radiotherapy within the last 4 weeks or > 25% of bone marrow.
• Patients with CNS metastases
• Patients with chronic diarrhea (at least for 3 months) or partial bowel obstruction.
• Malnutrition or loss of > 10% of body weight during the last month.
• Peripheral neuropathy ≥ grade 2
• Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer.
• Psychiatric illness or social situation that would preclude study compliance.
• Pregnant or lactating women.