A new regimen for S-1 therapy aiming at adverse reaction mitigation and prolonged medication by introducing a 1-week drug-free interval after each 2-week dosing session: efficacy and feasibility in clinical practice

Kimura, Yutaka; Kikkawa, Nobuteru; Iijima, Shöhei; Kato, Takeshi; Naoi, Yasuto; Hayashi, Tarō; Tanigawa, Tetsuya; Yamamoto, Hitoshi; Kurokawa, Eiji

doi:10.1007/s10120-003-0230-y

Cited by 36 publications

(24 citation statements)

References 11 publications

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“…(1) S-1-related adverse reactions commonly appear 2 -3 weeks after treatment starts (Nagashima et al, 2005); (2) a 2-week schedule showed the possibility of mitigated toxicity and prolonged the medication period (Kimura et al, 2003); (3) this schedule showed feasibility in heavily pretreated metastatic colorectal cancer (Jeung et al, 2006); and (4) recent phase I study of 2-week S-1 schedule demonstrated an antitumour activity in chemotherapy-refractory gastric cancer, with a similar pharmacokinetic profile to the conventional schedule (Zhu et al, 2007).…”

Section: S-1 Monotherapy In Poor Performance Status H-c Jeung Et Almentioning

confidence: 99%

A phase II study of S-1 monotherapy administered for 2 weeks of a 3-week cycle in advanced gastric cancer patients with poor performance status

et al. 2007

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Systemic chemotherapy for gastric cancer is often associated with treatment-related toxicity, which is particularly severe in patients with a poor performance status. In this paper, we describe the first study to evaluate S-1 monotherapy as an option for advanced gastric cancer patients who are not candidates for combination chemotherapy due to poor clinical condition. Fifty-two patients with Eastern Cooperative Oncology Group (ECOG) performance scale 2 -3, whose general condition had made use of combination chemotherapy impossible, were enrolled. S-1 was administered to 30 patients as second-or third-line therapy. The initial dose of S-1 was 35 mg m À2 , administered b.i.d for 14 days every 3 weeks. With a median follow-up period of 33 weeks, the median progressionfree survival, and overall survival were 11 weeks (95% CI, 8 -14) and 33 weeks (95% CI, 19 -47), respectively. The overall 1-year survival rate was 29% by intent-to-treat analysis. The overall response rate was 12% (95% CI, 3 -21), and the percentage of stable disease was 35%, resulting in the disease control rate of 47% (95% CI, 32 -60). Significant drug-related toxicity included grade 3 diarrhoea (14%), anorexia (14%), fatigue (10%), neutropenia (10%), and leucopenia (6%). In conclusion, this study indicated the modest activity of S-1 in gastric cancer patients with poor performance status.

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Section: S-1 Monotherapy In Poor Performance Status H-c Jeung Et Almentioning

confidence: 99%

A phase II study of S-1 monotherapy administered for 2 weeks of a 3-week cycle in advanced gastric cancer patients with poor performance status

et al. 2007

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“…They also reported that the total 6-month compliance for S-1 was much more favorable for the 2-week regimen than for the 4-week regimen. These authors concluded that the 2-week regimen may mitigate adverse reactions and prolong the medication period (19). In the present study, S-1 was administered orally for 14 consecutive days, followed by a 7-day rest (2-week regimen).…”

Section: S1 Group (N=26) --------------------------------------------mentioning

confidence: 79%

Effects of S-1 as a second-line chemotherapy for patients with relapsed pancreatic cancer

et al. 2011

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Abstract. Adjuvant chemotherapy with gemcitabine is the standard treatment in Japan for patients who have undergone resection of pancreatic cancer. However, few reports have described suitable regimens for patients who present cancer relapse following adjuvant chemotherapy. In the present study, we retrospectively evaluated the efficacy and safety of S-1, an oral fluoropyrimidine derivative, as a second-line chemotherapy for patients who had suffered relapse of pancreatic cancer following adjuvant chemotherapy with gemcitabine. A total of 51 patients with pancreatic cancer suffered relapse after curative resection and subsequent adjuvant chemotherapy with gemcitabine at our institution. A group of 26 of these patients were administered S-1 orally twice daily after meals at a dose of 80 mg/m 2 for body surface areas for 14 consecutive days, followed by a 7-day rest (S-1 group). The remaining 25 patients received no additional anticancer drugs other than continuation of gemcitabine (GEM/BSC group). During a median follow-up period of 35 months, a significant difference was observed in overall survival (OAS) between the S-1 group and the control group (median OAS, 20.9 vs. 13.7 months; p=0.0157, log-rank test). Furthermore, there was a significant inter-group difference in survival after relapse (SAR) (median SAR, 11.4 vs. 6.20 months; p=0.0025,. No increase in grade 3/4 hematological and non-hematological toxicity was observed in the S-1 group. In conclusion, second-line chemotherapy using a combination of S-1 and adjuvant chemotherapy with gemcitabine may be an efficient and beneficial strategy for patients with relapsed pancreatic cancer.

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“…At 80 mg/m 2 , there was no difference in grade III-IV diarrhea between Korean and European patients, but at the 70 mg/m 2 dose, diarrhea was slightly more common in European patients compared to Korean and Japanese patients (Table 3). In a small Japanese retrospective study comparing a 4-2-week schedule (4-week treatment and 2-week rest) and a 2-1-week schedule (2-week treatment and 1-week rest), the incidence of overall toxicity was lower for the 2-1-week schedule (77% versus 93%), while the response rates were similar in the two schedules (23% versus 21%) [13]. Anemia was the major toxicity in a phase II trial conducted with the 2-1-week schedule in Korean patients who had a poor performance status [14].…”

Section: Ethnic Differences In S-1 Adverse Eventsmentioning

confidence: 98%

Prediction of S-1-induced anemia

Chung

2009

Gastric Cancer

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inhibiting activity, and otastat potassium, which reduces the gastrointestinal toxicity [1].Derived from phase I data, Japanese early phase II studies of S-1 adopted a fi xed dose of 75 mg twice a day. However, skin rash and diarrhea hindered further conduct of the trial, and the dose was reduced to 50 mg twice a day. In consideration of the safety profi les of the fi xed-dose schedule, the dose of the late phase II trials was modifi ed to 80 mg/m 2 according to the body surface area (BSA). The applied dose ranged from 64 mg/m 2 to 80 mg/m 2 with a graded system; 80 mg for BSA less than 1.25 m 2 , 100 mg for BSA 1.25-1.50 m 2 , and 120 mg for BSA more than 1.5 m 2 . This BSA-based dosing system differed from the Western dosing system in that it fi xed the dosage for patients with a BSA greater than 1.5 m 2 . As a result, in patients with a BSA of more than 1.5 m 2 , the actual administered dose is not 80 mg/m 2 and there is a risk of underdosing. However, the safety profi le using this system is better than with a fi xed dosing schedule, and S-1 with this dosing system has been the preferred oral agent for the treatment of gastric cancer in Japan.Based on the Japanese response evaluation criteria, which include primary gastric cancer as a measurable lesion, S-1 demonstrated excellent activity in patients with advanced gastric cancer, with a response rate of 45%-54% in early phase II Japanese trials [2][3][4]. In these trials, even though the incidence of overall toxicity was as high as 83%, the toxicity profi le was mild, with a less than 10% incidence of grade III or IV toxicities. And in a post-marketing survey, the incidence of toxicity was 74.1% with the 80 mg/m 2 Japanese dosing system with 4-week treatment and a 2-week rest schedule. This incidence of general toxicity was almost equal to that in the pre-marketing clinical trials. The major reasons for discontinuation of S-1 during the fi rst or second cycle of the treatment were disease symptom progression (43%) or toxicities (33%). The adverse reactions during each cycle appeared mainly during the 2-3 weeks after Abstract S-1, a novel oral fl uoropyrimidine, has shown remarkably good tolerability in Korean gastric and colorectal cancer patients due to its favorable safety profi le. Myelosuppression and diarrhea were the events that precluded dose escalation in Japan, whereas gastrointestinal toxicity and skin reaction were the major limiting factors in Western countries. In contrast, the major adverse event in Korean patients was anemia, which appeared early in the S-1 treatment period and varied among patients. Conventional comparative genomic hybridization (CGH) is used to screen for chromosomal copy number variations such as gene gain, loss, amplifi cation, and deletion. This technique can provide information about genetic instability and chromosomal rearrangements. However, the low resolution of 5-10 Mb is a caveat with conventional CGH. cDNA microarray-based CGH is a useful technique for achieving higher resolution for the detection of genomic aberra...

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A new regimen for S-1 therapy aiming at adverse reaction mitigation and prolonged medication by introducing a 1-week drug-free interval after each 2-week dosing session: efficacy and feasibility in clinical practice

Cited by 36 publications

References 11 publications

A phase II study of S-1 monotherapy administered for 2 weeks of a 3-week cycle in advanced gastric cancer patients with poor performance status

A phase II study of S-1 monotherapy administered for 2 weeks of a 3-week cycle in advanced gastric cancer patients with poor performance status

Effects of S-1 as a second-line chemotherapy for patients with relapsed pancreatic cancer

Prediction of S-1-induced anemia

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