Multicenter phase II study of weekly paclitaxel plus S-1 combination chemotherapy in patients with advanced gastric cancer

Abstract

prognosis of advanced gastric cancer is still poor, chemotherapies were reported to improve the overall survival compared to the best supportive care in several studies [2][3][4]. Among the various active chemotherapeutic agents, cisplatin-based chemotherapy is the most commonly used worldwide. The V-325 study demonstrated that adding docetaxel (D) to a frequently used regimen of cisplatin and 5-fl uorouracil (CF) provided benefi ts with regard to overall survival, response rate, time to disease progression, clinical benefi t, and healthrelated quality of life [5]. Although the DCF regimen provides these advantages, it is accompanied by an increase in toxicity compared with the doublet regimen. The toxicity profi le of DCF is acceptable only with appropriately selected patients and comprehensive toxicity management strategies [6]. In this regard, the development of less toxic new combination chemotherapy has still been considered necessary to properly treat those patients with advanced gastric cancer.Paclitaxel, (Taxol; Bristol-Myers Squibb, Princeton, NJ, USA), which is derived from the bark of the Pacifi c yew, Taxus brevifolia, is one of the most active anticancer drugs for the treatment of solid tumors, effectively blocking cancer cells in the G2/M phase through the inhibition of microtubular depolymerization [7,8]. An administration schedule at doses of 175-225 mg/m 2 by intravenous infusion every 3 weeks has been widely accepted [9]. In addition, several phase II studies have shown that paclitaxel, alone or in combination with cisplatin or 5-fl uorouracil (5-FU), is also active against advanced gastric cancer [10-13]. However, a relatively high incidence of grade 3 or 4 neutropenia (14%-35%) is one of the major adverse effects.Paclitaxel is known to be a cell-cycle-specifi c agent, and in vitro experiments have suggested that prolonged Results. A total of 54 patients were registered. All of them had measurable disease and were determined to be eligible for the present study. Two complete responses and 23 partial responses were confi rmed, giving an overall response rate of 46.3%. At a fi nal follow up of 3 years, the median progressionfree survival and median overall survival were 6.0 and 14.3 months, respectively. Grade 3 neutropenia occurred in 14 patients, and grade 4 in 1 patient (total, 27.8%). The most serious nonhematological toxicity was diarrhea, where grade 3 occurred in 5 patients (9.3%). There were no treatmentrelated deaths. Conclusion. A combination of weekly paclitaxel plus S-1 was found to be well tolerated and effective in patients with advanced gastric cancer. Further investigation with comparative trials is needed for confi rmation.

Effect of the Weekly Administration of Liposome–Paclitaxel Combined with S-1 on Advanced Gastric Cancer

“…Other observed treatment related toxicities such as fatigue, vomiting, diarrhea were well tolerated. In the study of Yuji Ueda (37), neutropenia occurred with Grade-3 intensity in 14 patients (25.9%), Grade-4 neutropenia was observed in 1 patient, and Grade-3 anemia was observed in 7 patients (13.0%). The Grade-3 nonhematological toxicities were diarrhea (9.3%), anorexia (7.4%) and nausea (7.4%).…”

“…Several Phase-I and Phase-II studies have reported the efficacy and toxicity of the weekly administration of paclitaxel and S-1 in AGC, suggesting that this regime is effective and safe for this kind of patients (38 -40). Yuji Ueda et al (37) reported that among 54 patients with AGC, an overall response rate of 46.3%, a median PFS of 6.0, and a median OS of 14.3 months are observed. In this multicenter Phase-II study on the weekly administration of paclitaxel plus S-1 combination chemotherapy, paclitaxel is administered at 50 mg/m 2 on days 1, 8 and 15 and S-1 at 80 mg/m 2 on days 1 -14 followed by 2 weeks off in a 28-day cycle.…”

A phase II study of biweekly S-1 and paclitaxel (SPA) as first-line chemotherapy in patients with metastatic or advanced gastric cancer

“…We hypothesize that an alternative treatment schedule of S-1 (1-week administration followed by 1-week rest) may further reduce the toxicities and allow continuation of the therapy. Recent studies have shown enhanced antitumor activity of S-1 with paclitaxel in AGC [9][10][11][12]. Given the scarcity of study on biweekly S-1 and paclitaxel (SPA) as first-line chemotherapy in patients with metastatic or advanced gastric cancer, the actual efficacy and safety of this regimen is in need of more research.…”

A randomized phase-II trial comparing sequential and concurrent paclitaxel with oral or parenteral fluorinated pyrimidines for advanced or metastatic gastric cancer

“…One of the promising agents was paclitaxel (PTX) [8], which had shown beneficial results in single use or concurrent use with a fluoropyrimidine [9][10][11][12]. However, these studies were conducted as single-arm phase I-II trials.…”

“…We therefore planned a randomized phase-II trial to compare the following four treatment regimens: A, sequential 5-FU monotherapy followed by PTX monotherapy; B, sequential S-1 monotherapy followed by PTX monotherapy; C, concurrent 5-FU plus PTX [11]; and D, concurrent S-1 plus PTX [12]. The purpose of the study was twofold: (1) to compare S-1 with infusional 5-FU to determine which was the better partner of PTX, and (2) to compare a concurrent strategy with a sequential one, the latter strategy being the one that is widely used in Japanese general practice.…”