Efficacy and safety of cisplatin and capecitabine in combination as first line treatment for unselected patients with advanced gastric cancer

Combination chemotherapy is the most effective therapy in order to prolong survival and increase quality of life in patients with advanced or metastatic gastric cancer [1 3] and renders consistently survival benefit when compared with best supportive care, achieving moderate response rates, in the range of 15 50% [1,3,4]. At the present, the median survival of patients with metastatic disease remains between six and nine months [1,3,4] and no regimen has demonstrated superiority [5]. Kim et al. [6] conducted a phase II trial with a combination of cisplatin 60 mg/m on day 1 and capecitabine 1250 mg/m twice daily days 1 14 every three weeks. They achieved an overall response rate (ORR) of 55% and the median overall survival (OS) was 10.1 months, with an acceptable toxicity. To this promising results must be added the outstanding convenience of this regimen: since there is no need for catheters or pumps for continuous chemotherapy infusion, it lessens the number of visits, the morbidity and the inconvenience of other combinations. However, we wanted to find out to what extent these results could be obtained in our daily practice. Patients with metastatic gastric adenocarcinoma usually present poor general condition, under nourishment, advanced age, and co-morbidity. These features can determine worse prognosis, lower response rate, shorter survival and increased toxicity, although do not formally contraindicate chemotherapy. Thus, increasing quality of life, lessening toxicity and considering patients? convenience are a major concern, since advanced gastric cancer treatment is directed toward life extension and symptom palliation rather than cure. From March 2003 to September 2004, 36 patients with ECOG performance status 0 2 and histologically confirmed, non-resectable gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction were enrolled. Their characteristics are listed in Table I. All patients gave written informed consent as approved by the Ethical Committee. A total of 140 cycles were administered. The mean number of cycles per patient was 3.9 (range: 1 8). Delays and dose reductions were mainly due to hematologic and gastrointestinal toxicity. The dose intensity was 17.6 mg/m/week for cisplatin and 9729 mg/m/week for capecitabine (88% and 83% of the planned dose respectively). All patients were assessed for toxicity according to NCI-CTC v2.0. The incidence of grade 3 4 diarrhea was 25%, while 14% of patients presented grade 3 4 mucositis and only 8% of them suffered grade 3 4 emesis (very light, probably due to the relative low dose of cisplatin). Despite the high doses of capecitabine administered only 8% experienced grade 3 hand-foot syndrome, dose limiting toxicity of capecitabine in phase I trials [7]. Hematological toxicity predominated: 19% of patients presented grade 3 4 neutropenia while 5% experienced grade 3 anemia and 8% grade 3 thrombocytopenia. There was a high incidence of grade 4 febrile neutropenia, four patients (11%), two of them with fast recovery and the other two resulting in toxic deaths. Another toxic death occurred in a patient who developed acute renal failure due to grade 4 diarrhea and