Gemcitabine and S-1 for Advanced Biliary Tract Cancer
Ключевые слова
абстрактный
Описание
Biliary-tract cancer (BTC) is invasive carcinoma that originates from the epithelial lining of the gallbladder and bile ducts. BTC include cholangiocarcinoma (intrahepatic, perihilar, and distal biliary-tree tumor) and carcinoma arising from the gallbladder.
Surgical resection of the primary tumor is potentially curative for BTC, but less than a quarter of patients are eligible for resection at presentation. Systemic chemotherapy is the principal treatment method for patients with unresectable or metastatic BTC.
Gemcitabine is a promising agent, which has shown efficacy in biliary tract cancer. As a single-agent therapy, gemcitabine shows response rates of 8-36% in BTC[4]. In phase II trials with patients in advanced BTC, gemcitabine in combination with capecitabine or platinum analogues produced objective response rates of 26-50%.
The ABC-02 study reported a significant survival advantage for gemcitabine and cisplatin over gemcitabine alone in patients with advanced BTC (median overall survival 11.7 vs. 8.1 months; P < 0.001).
Oral anticancer drug S-1 consists of the 5-FU prodrug tegafur with two biochemical modulators, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo). S-1 monotherapy is active against advanced BTC with objective response rates of 21-35%, and phase II trials of S-1 in combination with gemcitabine reported objective response rates of 20-36%. Differences between trials in the doses and administration schedules of gemcitabine and S-1 may be reflected in the ranges of efficacy, dose-intensity, and rates of toxicity observed.
Even though the efficacy of gemcitabine and S-1 combination is evident for patients with advanced BTC in previous phase II trials, there was no clinical study investigating the efficacy of gemcitabine and S-1 combination for patients with advanced BTC when this study was started. Therefore, we conducted a phase II study to evaluate gemcitabine and S-1 combination as first-line chemotherapy for patients with advanced BTC.
Даты
| Последняя проверка: | 04/30/2014 |
| Первый отправленный: | 05/18/2014 |
| Предполагаемая регистрация отправлена: | 05/20/2014 |
| Первое сообщение: | 05/25/2014 |
| Последнее обновление отправлено: | 05/20/2014 |
| Последнее обновление опубликовано: | 05/25/2014 |
| Фактическая дата начала исследования: | 07/31/2005 |
| Предполагаемая дата завершения начальной школы: | 10/31/2010 |
| Предполагаемая дата завершения исследования: | 11/30/2013 |
Состояние или болезнь
Вмешательство / лечение
Drug: gemcitabine and S-1
Фаза
Группы рук
| Рука | Вмешательство / лечение |
|---|---|
| Experimental: gemcitabine and S-1 | Drug: gemcitabine and S-1 Treatment will be delivered as a 3-week cycle.
Gemcitabine 1000 mg/m2 iv on day 1, 8
S-1 60 mg/day po on day 1-14 |
Критерии приемлемости
| Возраст, имеющий право на обучение | 18 Years Чтобы 18 Years |
| Полы, имеющие право на обучение | All |
| Принимает здоровых добровольцев | да |
| Критерии | Inclusion Criteria: - Unresectable, locally advanced, metastatic adenocarcinoma arising from the intra- and extrahepatic biliary ducts or gallbladder - Initially diagnosed or recurred - At least one bidimensionally measurable lesion, defined as at least 1x1cm with clearly defined margins on physical examination, on 3-dimentional CT, MRI, or PET-CT - Age ≥18 and ≤70 years - Estimated life expectancy ≥3 months - ECOG performance status ≤2 - Adequate bone marrow function (WBCs ≥4,000/µL or absolute neutrophil count ≥1,500/µL, platelets ≥100,000/µL), - Adequate kidney function (creatinine ≤1.4 mg/dL) - Adequate liver function (bilirubin ≤1.8 mg/dL, transaminase levels ≤100mg/dL) - Written informed consent Exclusion Criteria: - Other tumor type than adenocarcinoma - Previous history of chemotherapy (exception : adjuvant chemotherapy) - Presence of CNS metastasis, psychosis, or seizure - Obvious bowel obstruction - Evidence of serious gastrointestinal bleeding - Past or concurrent history of neoplasm other than biliary adenocarcinoma, except for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix uteri - Pregnant or lactating women, women of childbearing potential not employing adequate contraception - Other serious illness or medical conditions |
Результат
Основные показатели результатов
1. Objective reponse rate [1 year]
Меры вторичного результата
1. Progression free survival, median overall survival, disease control rate, and over grade 3 hematologic toxicities (neutropenia, thrombocytopenia, and febrile neutropenia) [1 year]
