Gastric carcinoma continues to be a significant health
problem despite its decreasing incidence. It remains the second most common
malignant disorder in the world, accounting for more than 750,000 new cases and
more than 500,000 deaths each year. It is the number 1 cause of
cancer-related death in many countries. Although the incidence of gastric
carcinoma is one of the lowest of all malignancies in North America, gastric
carcinoma is the eighth leading cause of cancer death in the United States. It
was estimated that in 2002, there would be more than 21,600 new cases of gastric
carcinoma in the United States and 12,400 deaths. At the time of diagnosis,
approximately 50% of gastric carcinoma patients have metastatic disease.
Although advanced disease remains incurable, chemotherapy can be palliative.
Compared with best supportive care alone, combination chemotherapy improved
quality of life and overall survival in four small randomized trials.[3-6] Once
patients have not responded to front-line chemotherapy (often fluorouracil- or
cisplatin-based), there is no established second-line chemotherapy for these
The combination of irinotecan (CPT-11, Camptosar) and cisplatin has
demonstrated activity as first- and second-line therapy for gastric
carcinoma. We performed a phase II trial of this regimen using a previously
established treatment schedule in patients who have had at least one previous
systemic chemotherapy. Preliminary results are presented here.
Patients with histologic proof of advanced gastric or gastroesophageal
adenocarcinoma, with measurable disease, were eligible for inclusion in the
study. They were required to have an absolute granulocyte count of 1,500/µL or
a hemoglobin level of 8 g/dL or more, and a platelet count of 100,000/µL or
bilirubin level of 1.5 mg/dL or less, serum creatinine level of 1.5 mg/dl or
expectancy of more than 3 months; and a performance status of 2 or less on the
Zubrod scale. Patients must have received at least one previous chemotherapy
regimen (that did not include a topoisomerase I inhibitor). The Institutional
Review Board approved the study, and all patients provided written informed
Pretreatment evaluation included a complete blood cell count, multichannel
chemical survey, and electrolyte measurement. All patients underwent computed
tomography of the abdomen and pelvis (if indicated), chest radiography, and
other imaging studies if necessary. A complete history was obtained and a
physical examination was performed prior to study entry.
Chemotherapy consisted of 50 mg/m² of irinotecan given intravenously (IV)
over 90 minutes followed by 30 mg/m² of cisplatin IV over 60 minutes. Both drugs
were administered 1 day per week for 4 consecutive weeks, followed by a recovery
period of 2 weeks. Thus, one cycle was 6 weeks long (4 weeks of therapy and 2
weeks of recovery).
Chemotherapy was administered in the outpatient setting. All patients
received hydration before and after the cisplatin, and were premedicated with IV
dexamethasone, lorazepam, and ondansetron (Zofran) to prevent emesis. Patients
received extensive verbal and written instructions regarding early therapy for
diarrhea; they were given oral medications to reduce the severity of delayed
nausea and vomiting, and loperamide to reduce the severity of diarrhea. Standard
response and toxicity definitions were used.
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