Phase II Study of Bolus 5-Fluorouracil and Leucovorin Combined with Weekly Paclitaxel as First-Line Therapy for Advanced Gastric Cancer

Abstract

Objective: We evaluated the efficacy and safety of bolus 5-fluorouracil (5-FU) and leucovorin combined with weekly paclitaxel (FLTAX) in advanced gastric cancer (GC) patients. Methods: Patients with untreated stage IV GC received paclitaxel 80 mg/m² as a 1-hour infusion, followed by 5-FU 600 mg/m² as a bolus infusion and L-leucovorin 250 mg/m² as a 2-hour infusion on days 1, 8 and 15. Treatment cycles were repeated every 28 days. The primary endpoint was response rate. Results: Thirty-five patients were enrolled. The median age was 62 years (range 34–75). Twenty-one patients (60%) had diffuse-type cancer and 11 had peritoneal metastasis. The confirmed response rate was 43% (95% CI 26–61) with 15 partial responses. Stable disease was observed in 16 (46%) patients. Median progression-free survival and overall survival were 6.8 months (95% CI 5.8–7.4) and 16.2 months (95% CI 10.0–22.8), respectively. Grade 3–4 adverse events were: neutropenia (54%), febrile neutropenia (3%), diarrhea (6%) and sensory neuropathy (11%). Conclusion: FLTAX showed a desirable safety profile, and the efficacy against advanced GC was encouraging. FLTAX may be a good option for GC patients with deteriorated general condition, and a randomized clinical trial in such patients is currently underway.

Randomized phase II/III study of 5-fluorouracil/l-leucovorin versus 5-fluorouracil/l-leucovorin plus paclitaxel administered to patients with severe peritoneal metastases of gastric cancer (JCOG1108/WJOG7312G)

“…Moreover, paclitaxel has been reported its synergistic effect in vitro when followed by 5-FU [16], and these 2 drugs are relatively free of overlapping toxic effects. We developed 5-FU/l-LV plus paclitaxel (FLTAX) therapy for such patients, which involves weekly administration without requiring hydration or oral agents [17,18]. Toxicity of FLTAX is mild, and doses were lower than the recommended dose for patients with advanced GC without severe PM.…”

Superior Antitumor Activity of Nanoparticle Albumin-Bound Paclitaxel in Experimental Gastric Cancer

“…Mitotic cell death is a mode of cell death occurring specifically during mitotic stages induced by DNA damaging agents and spindle poisons/mitotic inhibitors [16], [17]; it is mainly caspase dependent, but under rare circumstances can also be caspase independent [18]. Paclitaxel has been tested for advanced and recurrent gastric cancers with a response rate of 43% in combination with 5-fluorouracil and folinic acid [9], [19]. Compared to the response rate of 38∼45% yielded by a combination of oxaliplatin with 5-fluorouracil and folinic acid, paclitaxel did not result in superior survival but caused more side effects, especially in elderly patients [9], [20]–[22].…”

“…Paclitaxel has been tested for advanced and recurrent gastric cancers with a response rate of 43% in combination with 5-fluorouracil and folinic acid [9], [19]. Compared to the response rate of 38∼45% yielded by a combination of oxaliplatin with 5-fluorouracil and folinic acid, paclitaxel did not result in superior survival but caused more side effects, especially in elderly patients [9], [20]–[22]. Paclitaxel required emulsification with solvents to allow intravenous administration which has resulted in hypersensitivity reactions and potentially dramatic side effects in patients [23], [24].…”

Swainsonine inhibits growth and potentiates the cytotoxic effect of paclitaxel in hepatocellular carcinoma in vitro and in vivo

“…Currently, many researchers have focused their efforts on exploring chemosensitizing drugs, with NF-κB suppression activity, used in combination with other chemotherapeutic agents for effective management of HCC (37). Paclitaxel is a useful chemotherapeutic drug for the treatment of patients with a variety of malignant tumors (38). However, chemoresistance due to paclitaxel-induced NF-κB activation is an important cause of the limits of paclitaxel efficacy (39).…”