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 patients.
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 more, a hemoglobin level of 8 g/dL or more, and a platelet count of 100,000/µL or more; serum bilirubin level of 1.5 mg/dL or less, serum creatinine level of 1.5 mg/dl or less; life 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 consent.
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.
1. Parkin DM, Pisani P, Ferlay J: Global cancer statistics. CA Cancer J Clin 49:3-64, 1999.
2. Jemal A, Thomas A, Murray T, et al: Cancer statistics 2002. CA Cancer J Clin 52(1):23-47, 2002.
3. Murad AM, Santiago FF, Petroianu A, et al: Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer 72:37-41, 1993.
4. Pyrhonen S, Kuitunen T, Kouri M: A randomized, phase III trial comparing fluorouracil, epidoxorubicin and methotrexate (FEMTX) with best supportive care in non-resectable gastric cancer (abstract). Ann Oncol 3(suppl):12, 1992.
5. Glimelius B, Hoffmann K, Haglund U, et al: Initial or delayed chemotherapy with best supportive care in advanced gastric cancer. Ann Oncol 5:189-190, 1994.
6. Scheithauer W, Komek G, Zeh B, et al: Palliative chemotherapy versus supportive care in patients with metastatic gastric cancer. A randomized trial (abstract). Second International Conference on Biology, Prevention, and Treatment of GI Malignancy, p 68. Koln, Germany, 1995.
7. Ajani JA, Baker J, Pisters PW, et al: CPT-11 plus cisplatin in patients with advanced, untreated gastric or gastroesophageal junction carcinoma . Results of a phase II study. Cancer 2002 (in press).
8. Saltz LB, Spriggs D, Schaaf LJ, et al: Phase I clinical and pharmacologic study of weekly cisplatin combined with weekly irinotecan in patients with advanced solid tumors. J Clin Oncol 16:3858-3865, 1998.
9. Kambe M, Wakui A, Nakao I, et al: A late phase II study of irinotecan (CPT-11) in patients with advanced gastric cancers (abstract 584). Proc Am Soc Clin Oncol 12:198, 1993
10. Shirao K, Shimada Y, Kondo H, et al: Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer. J Clin Oncol 15:921-927, 1997.
11. Boku N, Ohtsu A, Shimada Y, et al: Phase II study of a combination of irinotecan and cisplatin against metastatic gastric cancer. J Clin Oncol 17:319-23, 1999.