A phase I/II study of S-1 plus cisplatin in patients with advanced gastric cancer: 2-week S-1 administration regimen

Sato, Yasuhiro; Kondo, Hitoshi; Honda, Kana; Takahari, Daisuke; Sumiyoshi, Tetsuya; Tsuji, Yasushi; Yoshizaki, Naohito; Niitsu, Yoshiro

doi:10.1007/s10147-004-0451-z

Cited by 16 publications

(16 citation statements)

References 15 publications

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“…The SP regimen in our study was well tolerated, similar to the results in previous studies [4,[6][7][8][9][10].…”

Section: Discussionsupporting

confidence: 89%

“…A moderate to high dose of cisplatin is usually administered every 3-5 weeks to patients with advanced gastric cancer [4][5][6][7][8][9][10]; however, excessive hydration is vital to prevent renal toxicity at this dose. To reduce the necessity for excessive hydration and decrease renal toxicity, split-or low-dose cisplatin combined with S-1 has been investigated in several phase I and II studies [11][12][13][14][15] using various doses and schedules (S-1 administered at 80 mg/m 2 for 14-28 days and cisplatin infused at 10 mg/m 2 /day twice a week [11], 25 mg/m 2 /day once a week [12,13], or 4 mg/m 2 /day for 5 consecutive days/week [14]).…”

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confidence: 99%

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A randomized phase II study comparing S-1 plus weekly split-dose cisplatin with S-1 plus standard-dose cisplatin as first-line chemotherapy for advanced gastric cancer

et al. 2013

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Background S-1 plus weekly split-dose cisplatin demonstrated promising results in previous phase I and II studies for advanced gastric cancer (AGC) patients. Methods In this randomized phase II study, the efficacy and safety of S-1 plus weekly split-dose cisplatin (SWP, S-1 daily oral dose of 80-120 mg according to body surface area on days 1-14, and cisplatin 20 mg/m 2 i.v. on days 1 and 8 every 3 weeks) were compared with those of S-1 plus standard-dose cisplatin (SP) as first-line chemotherapy for AGC patients. The primary endpoint was 1-year survival rate.Results Patients were randomized into two groups: 18 in the SWP arm and 19 in the SP arm. This trial was terminated early because of low patient enrollment. The 1-year survival rate was 61 % [95 % confidence interval (CI), 36-86 %] and 53 % (95 % CI, 30-75 %) in the SWP and SP arms, respectively. However, the median survival time was 12.3 months (9.9-14.6 months) and 15.7 months (4.0-27.4 months), respectively (P = 0.064). Progressionfree survival was significantly shorter in the SWP arm than in the SP arm (P = 0.047). Toxicity tended to be milder in the SWP arm than in the SP arm. For approximately 40 % of patients in the SWP arm, cisplatin was omitted on day 8 and treatment delayed because of prolonged myelosuppression. Conclusions No clear benefits of adding cisplatin to S-1 in the SWP arm were demonstrated in this study. At this point, split-dose cisplatin combined with S-1 cannot be recommended for use in clinical practice.

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“…The SP regimen in our study was well tolerated, similar to the results in previous studies [4,[6][7][8][9][10].…”

Section: Discussionsupporting

confidence: 89%

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confidence: 99%

A randomized phase II study comparing S-1 plus weekly split-dose cisplatin with S-1 plus standard-dose cisplatin as first-line chemotherapy for advanced gastric cancer

et al. 2013

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“…Because a standardized schedule of S-1 and cisplatin in combination has not been established, several doses and schedules were evaluated [8,11,12]. Although a 5-week schedule (3 weeks on and 2 weeks off) has been used primarily in Japan [10], the dose of cisplatin was relatively lower in this schedule than in other phase III studies [13,14].…”

Section: Introductionmentioning

confidence: 99%

Three-week combination chemotherapy with S-1 and cisplatin as first-line treatment in patients with advanced gastric cancer: a retrospective study with 159 patients

et al. 2011

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Background Doses and schedules of the combination of S-1 and cisplatin for the treatment of advanced gastric cancer (AGC) have not been standardized. We therefore evaluated the efficacy and feasibility of a 3-week schedule of S-1 and cisplatin in patients with AGC, as well as assessing factors prognostic of patient outcomes. Methods A total of 159 patients with AGC were treated with S-1 (40 mg/m 2 bid on days 1-14) and cisplatin (60 mg/m 2 IV on day 1) between January 2004 and December 2008. Results Median follow-up duration was 20.0 months (range, 11.4-48.5 months), during which time 129 patients (81.1%) died. Patients received a median 6 cycles of chemotherapy (range, 1-19 cycles). Among the 59 patients with measurable disease, 1 achieved a complete response (1.7%) and 24 (40.7%) had partial responses, giving an overall response rate of 42.4% (95% CI, 23.0-61.8%). The median progression-free survival (PFS) was 5.8 months (95% CI, 4.8-6.9 months), and the median overall survival (OS) was 11.3 months (95% CI, 9.6-13.0 months). Multivariate analysis showed that initial metastasis, bone metastasis, and liver metastasis were independent prognostic factors for reduced PFS, whereas poor performance status, initial metastasis, and bone metastasis were prognostic for reduced OS. Application of a previous prognostic model showed that observed PFS and OS survival curves for patients in various risk groups differed significantly (P \ 0.001 each). Conclusions A 3-week regimen of S-1 plus cisplatin was active and well tolerated as first-line treatment in patients with AGC. Disease status and bone metastasis were the most important prognostic factors.

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“…Leucopenia, neutropenia, anemia, and diarrhea were the most common adverse effects. As shown in Table 1, however, the dose intensity of cisplatin in most studies was lower than the dosages that have been widely accepted as reference regimens in advanced gastric cancer (20-25 mg/m 2 per week) [12,14,16,17].…”

Section: Introductionmentioning

confidence: 97%

“…tively [13,14]. In other studies, S-1 was fi xed at a standard dose of 80 mg/m 2 per day and the optimal dose of cisplatin was explored with different cycles, and these regimens showed antitumor activity with response rates ranging from 53% to 73% [15][16][17]. Toxicities were generally manageable.…”

Section: Introductionmentioning

confidence: 99%

Phase I/II studies of combination chemotherapy with S-1 and platinum in patients with previously untreated metastatic or recurrent gastric cancer

Kang

2009

Gastric Cancer

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Systemic chemotherapy plays a crucial role in treatment [3][4][5].Although combination chemotherapy has been studied extensively, there is no internationally accepted standard of care for patients with advanced gastric cancer [4][5][6][7]. Worldwide, the combination of 5-fl uorouracil (5-FU) and cisplatin is a mainstay in the treatment of advanced gastric cancer. Recently, oral fl uoropyrimidines have been emerging as a breakthrough treatment [6]. The use of oral agents has potential advantages, from patient convenience to avoiding the need for indwelling venous access and infusion pumps [7,8]. An oral fl uoropyrimidine, S-1, is a fourthgeneration fl uoropyrimidine containing tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate [9]. Interesting results have been accumulating in evaluating S-1 combination therapies, particularly with platinum drugs. In this study, we reviewed phase I/II studies of combination chemotherapy with S-1 and platinum in patients with metastatic or recurrent gastric cancer. S1 + cisplatin trials in AsiaThe combination of S-1 and cisplatin is logical, given the biochemical modulation it offers: the inhibition of methionine uptake into tumor cells by cisplatin results in the enhancement of 5-FU cytotoxicity [10]. Since the fi rst phase I trial of S-1 in 1997 [11], many phase I/II studies have been conducted in Japan and have yielded promising results.One of the notable results of the phase II studies of S-1 and cisplatin was reported by Koizumi et al. [12]. S-1 was administered daily at a dose of 80 mg/m 2 per day for 3 weeks, followed by a 2-week rest, with cisplatin at 60 mg/m 2 given on day 8. This regimen had a 5-week cycle, and the response rate was 74%. Using the same regimen, the authors of two other studies also reported high response rates, of 67% and 66.7%, respecAbstract Despite the progress in treatment protocols, gastric cancer remains a challenging disease. Systemic chemotherapy is of crucial importance for patients with metastatic or recurrent disease, and new developments in chemotherapy regimens have been seen in recent years. An oral 5-fl uororacil (5-FU) agent, S-1, is emerging, with promising results. Various S-1 combination regimens, mostly with cisplatin, are being examined extensively, and the combination of S-1 with oxaliplatin is the focus of recent studies. In this study, phase I/II studies of combination chemotherapy with S-1 and platinum in patients with metastatic or recurrent gastric cancer were reviewed. We found that the combination of S-1 plus cisplatin was highly active against advanced gastric cancer, with a favorable toxicity profi le. The response rates were 53%-74% in Japan, 47.6% in Korea, and 51% in the United States and Europe. There is no internationally accepted standard care for patients with advanced gastric cancer yet, but S-1 is likely to replace infusional 5-FU, and oxaliplatin may represent an alternative to cisplatin in the near future. More innovative therapies, particularly with molecular-targeted drugs, are needed to meet the ...

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A phase I/II study of S-1 plus cisplatin in patients with advanced gastric cancer: 2-week S-1 administration regimen

Abstract: This regimen is considered to be generally well-tolerated and has substantial antitumor activity.

Cited by 16 publications

References 15 publications

A randomized phase II study comparing S-1 plus weekly split-dose cisplatin with S-1 plus standard-dose cisplatin as first-line chemotherapy for advanced gastric cancer

A randomized phase II study comparing S-1 plus weekly split-dose cisplatin with S-1 plus standard-dose cisplatin as first-line chemotherapy for advanced gastric cancer

Three-week combination chemotherapy with S-1 and cisplatin as first-line treatment in patients with advanced gastric cancer: a retrospective study with 159 patients

Phase I/II studies of combination chemotherapy with S-1 and platinum in patients with previously untreated metastatic or recurrent gastric cancer

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