Phase I study of weekly palliative chemotherapy with low-dose third-line paclitaxel for biliary tract cancer

The prognosis of patients with unresectable and recurrent biliary tract cancer (BTC) is very poor. Although gemcitabine (GEM) plus cisplatin therapy is useful for unresectable cases, the median overall survival (OS) of the patients is <1 year, and third-line chemotherapy following failure of 5-fluorouracil (5-FU) and GEM plus cisplatin is currently unavailable. The clinical efficacy and basic effects of low-dose paclitaxel (PTX) therapy for patients with BTC was previously reported. We herein present the results of a phase I clinical trial of weekly low-dose PTX as third-line palliative chemotherapy. PTX was administered on days 1, 8, 15 and 22 of each cycle and repeated twice as follows: Level 1, 40 mg/m²; level 2, 50 mg/m² (n=3). During the two cycles, grade 1 or 2 adverse events were observed in 3 patients, whereas dose-limiting adverse events (grade 3 or 4) were not observed. The disease control rate was 83.3% (partial response, n=3; stable disease, n=2). The OS and median survival were 15.4 and 9.0 months, respectively. In conclusion, palliative chemotherapy with low-dose PTX following failure of GEM and 5-FU was well-tolerated, safe and effective for patients with unresectable or recurrent BTCs, and the optimal dose was 50 mg/m².