RESUMEN
BACKGROUND: Irinotecan and S-1, an oral fluoropyrimidine composed of tegafur, gimeracil, and oteracil potassium, have demonstrated antitumor activity against advanced gastric cancer. We performed a phase 1/2 study to determine the recommended dose, antitumor activity, and safety of a combination of S-1 and irinotecan in patients with advanced gastric cancer. METHODS: Patients with previously untreated advanced gastric cancer were enrolled. Patients received irinotecan intravenously on days 1 and 15 plus oral S-1 twice daily on days 1-14 of a 28-day cycle. In the phase 1 part, the dose of irinotecan was escalated from 100 mg/m(2) to 125 mg/m(2) and then to 150 mg/m(2). RESULTS: A total of 24 patients were enrolled. Overall, the median number of treatment cycles per patient was 5.9, and 92% of the patients completed at least two cycles. The overall response rate was 54.2% (13 of 24). The response rates in differentiated and undifferentiated cancer were 56.3% (nine of 16) and 50.0% (four of eight), respectively. Median survival time was 581 days. The maximum tolerated dose of irinotecan was not reached at the highest level. However, grade 4 neutropenia occurred at 125 mg/m(2). We concluded that the recommended dose of irinotecan for the present regimen was 125 mg/m(2). CONCLUSION: Treatment with S-1+irinotecan is considered effective in patients with advanced gastric cancer who have not previously received chemotherapy. A combination of irinotecan and S-1 was well tolerated in patients with advanced gastric cancer and could be given on an outpatient basis.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Combinación de Medicamentos , Femenino , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Neoplasias Gástricas/patología , Tegafur/administración & dosificación , Tegafur/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Combined therapy with irinotecan/fluorouracil/levoleucovorin (calcium levofolinate) [IFL] has lost its position as the standard regimen for metastatic colorectal cancer because its toxicity and effectiveness have become controversial. OBJECTIVE: To (i) identify the optimal regimen for IFL therapy in terms of irinotecan dosage, and (ii) determine the maximum tolerated dose and efficacy of the modified-IFL regimen in patients with histologically confirmed advanced colorectal cancer. METHODS: In a phase I study, nine patients with advanced colorectal cancer received IFL treatment modified such that irinotecan was administered every 2 weeks, as opposed to the more toxic once-weekly administration. The study evaluated three escalating dose levels of irinotecan (100, 125 and 150 mg/m(2)). Each treatment cycle consisted of irinotecan on days 1 and 15; fluorouracil 600 mg/m(2) on days 1, 8, 15 and 22; and levoleucovorin 250 mg/m(2) on days 1, 8, 15 and 22. Data from the phase I study were used to determine the recommended dose of irinotecan for the phase II study. The latter study evaluated the effectiveness (overall response rate, median time to disease progression and median survival time) and tolerability of this modified-IFL therapy as ambulatory treatment in 22 patients with advanced colorectal cancer. RESULTS: The dose-limiting toxicity of irinotecan was grade 3 neutropenia, which occurred in three patients at dose level 2 (125 mg/m(2)); furthermore, a fourth patient developed grade 4 neutropenia at this dose level. Therefore, 125 mg/m(2) was considered to be the maximum tolerated dose, and the dose of irinotecan for the phase II study was set at 100 mg/m(2). Fourteen patients achieved partial response using this modified-IFL regimen, and the overall response rate was 63.6% (95% CI 43.5, 83.7). The median time to progression was 197 days (range 111-283 days) and the median survival time was 414 days (95% CI 116, 712). Toxicities were acceptable and manageable. CONCLUSIONS: Modified-IFL therapy is a practical, effective and tolerable option for ambulatory treatment of advanced colorectal cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adolescente , Adulto , Anciano , Atención Ambulatoria , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/fisiopatología , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Metástasis de la Neoplasia , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
We have previously reported on phase I/II studies of irinotecan plus S-1 therapy for advanced gastric cancer. Based on the safety and efficacy data that were obtained, this phase II study was planned to assess the efficacy of irinotecan plus S-1 for patients with advanced colorectral cancer. A total of 40 patients are enrolled at 13 medical institutions. The objective of this study was to establish a useful chemotherapy regimen for an out-patient setting.