As it is reported that the median survival time (MST) of clinical stage IV gastric cancer patients after curative surgery is less than 1 year, the outcome of highly advanced gastric cancer patients is still poor, regardless of adjuvant chemotherapy with conventional anticancer agents. A recent development of novel anticancer agents has improved a therapeutic outcome for advanced gastric cancer. The present main drug in Japan is S-1, which consists of a 5-fluorouracil (5-FU) prodrug (tegafur), a dihydropyrimidine dehydrogenase inhibitor [5-chloro-2,4-dihydroxypyrimidine (CDHP)], and an inhibitor of orotate phosphoribosyltransferase [potassium oxonate (oxonic acid)]. S-1 is easily used at outpatient with high efficacy rate and low toxicity, and it is also noted that S-1 shows better efficacy in combination with other anticancer drugs than S-1 alone. As chemo-radiation therapy has been recognized as one of the standard therapies for gastric cancer, radiation combined with effective chemotherapeutic regimens including S-1 will be an attractive therapy for such patients with poor prognosis with highly advanced gastric cancer.
This is the first report of the phase I/II study to attempt clarifying the beneficial effect and the toxicity with chemo-radiation therapy including S-1 in highly advanced gastric cancer patients. In the study, after determination of the recommended dose of low-dose CDDP at 6mg/m2/day in the phase I study, 30 cases with stage IIIB or IV gastric cancer were treated with S-1 at 80mg-120mg/body/day for 3 weeks, CDDP at 6mg/m2/day div, for 5 days followed by 2-day interval, and 40Gy (20 fraction of 2 Gy) radiation for 4 weeks, irradiating primary tumor and perigastric lymph nodes.
Clinical evaluation after the therapy showed 19 PRs (partial response), 8 NCs (no change), and 1 PD (progressive disease), resulting in 65.5% (19/29cases) of efficacy rate. Eight out of 30 patients underwent surgery, and 3 of these 8 patients showed a pathologically complete response (grade 3 effect) and the other 3 patients showed a partial response (grade 2 effect), suggesting that a high histological response (6/8 cases; 75.0%) is expected by the chemo-radiation. MST of these patients from the initial treatment reached to 18 months, suggesting a good prognostic outcome for such patients with expected poor prognosis. Approximately, 60% of the patients showed grade 3, 4 of bone marrow toxicity and 20% showed grade 3, 4 of gastrointestinal toxicity, while the most of the patients showed improvement of QOL including appetite.
Chemo-radiation with effective chemotherapeutic regimen with S-1 will be a potent regimen for obtaining high histological response with tolerable toxicity, and improving QOL in highly advanced gastric cancer patients.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA