Phase II study of S-1 and docetaxel combination in advanced or recurrent gastric cancer

Yoshida, Kensaku; Toge, Tetsuya; Ninomiya, Motoki; Takakura, N; Hirabayashi, N; Takiyama, Wataru; Sato, Yuki; Terashima, Masaaki; Goto, Masayuki; Sakamoto, Junya; Nishiyama, Masahiko

doi:10.1200/jco.2005.23.16_suppl.4049

Cited by 15 publications

(24 citation statements)

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“…In the combination chemotherapy with TS-1 plus systemic docetaxel administration, maximum tolerated doses were 80/50 mg/m 2 [25]. On the other hand, response rate achieved in 71.4% (5/7).…”

Section: Journal Of Surgical Oncologymentioning

confidence: 99%

Safety and efficacy of bidirectional chemotherapy for treatment of patients with peritoneal dissemination from gastric cancer: Selection for cytoreductive surgery

Yonemura¹,

Endou

Shinbo

et al. 2009

Journal of Surgical Oncology

116

112

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There is no standard treatment for peritoneal carcinomatosis (PC) from gastric cancer. New bidirectional chemotherapy (neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)) was developed. The aim of the present study was to assess the safety and efficacy of NIPS and to show the selection for cytoreductive surgery on PC from gastric cancer. Seventy-nine patients with PC from gastric cancer were treated with NIPS. A peritoneal port system was introduced into the abdominal cavity. The peritoneal wash cytological examination through a port was done before and after NIPS. The patients were treated with oral TS-1 twice a daily for 21 days, followed by a 1-week rest. On day 1, 8, and 15 from the start of oral TS-1 administration, 30 mg/m 2 of Docetaxel and 30 mg/m 2 of cisplatinum with 500 ml of saline were introduced into the peritoneal cavity through the port. A median course of oral TS-1 was 2.1 course and a median time of IP chemoterapy was 5.8. Peritoneal free cancer cells (PFCCs) had been detected in 65 (82.2%) patients before NIPS, and the positive cytology changed to be negative in 41 (63.0%) patients after NIPS. After NIPS, 41 patients underwent laparotomy, and complete cytoreduction was done in 32 (78%) patients. Complete cytoreduction was done in 27 (51.9%) of 52 patients with negative cytology but in only 4 (14.8%) of 27 patients with positive cytology (P < 0.001). Patients with negative cytology after NIPS survived significantly longer than those with positive cytology. The adverse effects after NIPS were mild and there was no treatment-related deaths. The grade 3/4 hematological adverse effects were found in 2 (2.6%) patients. Grade 3 renal toxicity and port site infection was found in three patients, respectively. NIPS using a port system is a safe and effective treatment for PC. Peritoneal wash cytology through a port system is a good indicator to select the patients to perform cytoreductive surgery.

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“…In the combination chemotherapy with TS-1 plus systemic docetaxel administration, maximum tolerated doses were 80/50 mg/m 2 [25]. On the other hand, response rate achieved in 71.4% (5/7).…”

Section: Journal Of Surgical Oncologymentioning

confidence: 99%

Safety and efficacy of bidirectional chemotherapy for treatment of patients with peritoneal dissemination from gastric cancer: Selection for cytoreductive surgery

Yonemura¹,

Endou

Shinbo

et al. 2009

Journal of Surgical Oncology

116

112

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“…Furthermore, we have recently demonstrated the tolerability and efficacy of TXT and S-1 combination chemotherapies. 25,26 However, little is known about the mechanisms underlying the synergistic effects of TXT upon either 5-FU or S-1. In the present study, we examined both the expression and activity profiles of enzymes that function in 5-FU metabolism, including TS, DPD and OPRT, so as to elucidate whether synergistic effects occur between TXT and S-1 against gastric cancer cells and to gain further insight into the mechanisms involved.…”

mentioning

confidence: 99%

Synergistic effects of docetaxel and S‐1 by modulating the expression of metabolic enzymes of 5‐fluorouracil in human gastric cancer cell lines

Wada

Yoshida

Suzuki

et al. 2006

Intl Journal of Cancer

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We have recently demonstrated in a Phase I/II study that combination chemotherapy with docetaxel (TXT) and S-1 is active against metastatic gastric carcinomas. To elucidate the mechanisms underlying the synergistic effects of these drugs, both the growth inhibitory effects and the expression profiles of enzymes involved in fluorouracil (5-FU) metabolism were examined in vitro and in vivo. TXT alone and in combination with 5-FU inhibited the growth of each of the 5 gastric cancer cell lines that we examined , in a time-and dosedependent manner. Moreover, striking synergistic effects were observed in TMK-1 cells in vitro with IC 50 values of between 4.73 and 0.61 nM 5-FU. Furthermore, in TMK-1 xenografts, 5-FU/ TXT cotreatments exhibited synergistic antitumor effects. The combination of S-1 and TXT, however, exhibited greater growthinhibitory effects than the 5-FU/TXT cotreatments. The mechanisms underlying these synergistic effects of S-1 and TXT were examined by expression and activity analyses of the 5-FU metabolic enzymes. The expression of thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) were decreased 50 and 73% of control levels, respectively, and that of orotate phosphorybosyl transferase (OPRT) was increased by 3.9-fold at the protein level. These findings suggested that biochemical modulation of the 2 drugs had occurred, which was further confirmed by the results of the activity assays. These data strongly indicate that a combination chemotherapy of TXT and S-1 is effective against gastric carcinomas and is therefore a good candidate as a standard chemotherapeutic strategy in treating these tumors. ' 2006 Wiley-Liss, Inc.Key words: gastric cancer; TMK-1; docetaxel; 5-fluorouracil; S-1; TS, thymidylate synthase; DPD, dihydropyrimidine dehydrogenase; OPRT, orotate phosphorybosyl transferase; combination effectIn spite of recent advances in the development of both diagnostic and therapeutic tools, gastric cancer is still a major cause of death throughout the world. Moreover, because many patients are still diagnosed at only the late stages of this disease, recurrent tumors are often detected even after curative surgery. In such patients, chemotherapy is one of the main treatment strategies that is employed, as it has been shown to improve prognoses. 1-3 However, a standard regimen of the treatment of metastatic gastric cancer has not been yet established in Japan.5-Fluorouracil (5-FU) is widely used an anticancer agent and is currently considered to be a key drug in clinical chemotherapeutic treatments for gastrointestinal cancers, such as esophageal, 4 gastric 5 and colorectal. 6 In addition, 5-FU has been also used to treat both breast 7 and cervical 8 cancers. 5-FU is catabolized to 2-fluorob-alanin by the first and rate-limiting enzyme of its metabolic pathway, dihydropyrimidine dehydrogenase (DPD). The functional effects of 5-FU are thought to occur through its active metabolite, 5-fluorodeoxyuridine diphosphate (FdUMP) 9,10 which, together with the coenzyme 5,10-methylenethtrahydr...

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“…[17][18][19][20] The difference in TTP between our two groups was about 60 days, but the difference in MST was about 200 days. This may have reflected the effect of second-line chemotherapy with agents such as taxanes or cisplatin and CPT-11, because more patients in the S-1 group received second-line chemotherapy compared with the non-S-1 group (47% vs 26%).…”

Section: Discussionmentioning

confidence: 83%

Retrospective analysis of stage IV advanced gastric cancer treated with S-1 or other chemotherapy

et al. 2006

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Patients treated with S-1 therapy had a better prognosis than patients without S-1. One metastatic site and being given second-line chemotherapy were other factors for better prognosis. For patients with only one metastatic site, a good prognosis can be obtained by second-line chemotherapy for those refractory to S-1. The prognosis of patients who had more than two metastatic sites remained poor; more effective chemotherapy might improve the survival of such patients if they retain good performance status.

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Phase II study of S-1 and docetaxel combination in advanced or recurrent gastric cancer

Cited by 15 publications

References 0 publications

Safety and efficacy of bidirectional chemotherapy for treatment of patients with peritoneal dissemination from gastric cancer: Selection for cytoreductive surgery

Safety and efficacy of bidirectional chemotherapy for treatment of patients with peritoneal dissemination from gastric cancer: Selection for cytoreductive surgery

Synergistic effects of docetaxel and S‐1 by modulating the expression of metabolic enzymes of 5‐fluorouracil in human gastric cancer cell lines

Retrospective analysis of stage IV advanced gastric cancer treated with S-1 or other chemotherapy

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