A multicenter phase II study of combined chemotherapy with docetaxel, cisplatin, and S-1 in patients with unresectable or recurrent gastric cancer (KDOG 0601)

Koizumi, Wasaburo; Nakayama, Norisuke; Tanabe, Satoshi; Sasaki, Takeshi; Higuchi, Katsuhiko; Nakamura, Ken; Takagi, Seiichi; Azuma, Mizutomo; Ae, Takako; Ishido, Kenji; Nakatani, Keiko; Naruke, Akira; Katada, Chikatoshi

doi:10.1007/s00280-011-1701-1

Cited by 68 publications

(45 citation statements)

References 12 publications

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“…In fact, preoperative chemotherapy with DCS was feasible, and the mean percentage of the actual/-planned dose was quite high, although the proportion of PS1 patients was 9 %, slightly higher than in our previous study (0 %). Meanwhile, the incidence of grade 3 or grade 4 febrile neutropenia from DCS therapy in the present study (5.7 %) was lower than that in the phase II study of the Kitasato regimen for unresectable or recurrent gastric cancer patients (13.6 %) [7]. The proportion of PS0 patients was 90.6 %, higher than that for the Kitasato regimen for unresectable or recurrent gastric cancer patients (67.8 %).…”

Section: Discussioncontrasting

confidence: 43%

“…The proportions of febrile neutropenia for the Sapporo [9], Kitasato [7], and Kanazawa [6] regimens were 16.1, 13.5, and 13.3 % respectively, whereas the RRs were 87.1, 81.3, and 76.1 % respectively. Since our previous study (JCOG0001) [3] was terminated early because of treatment-related deaths, the Kitasato regimen was used for its lower toxicity and higher RR among various DCS regimens.…”

Section: Discussionmentioning

confidence: 93%

“…In the present study, the number of preoperative chemotherapy cycles was specified in the protocol as only two courses if R0 resection was expected to be possible. The RR of DCS therapy in the phase II study of the Kitasato regimen [7] was high (81.3 %) for unresectable gastric cancer, but the proportion of patients who underwent DCS therapy and achieved partial response within two cycles among the responders was only 83.3 %, which means that the partial response rate within two cycles was only 67.7 % of all patients (personal communication). Thus, the number of chemotherapy cycles might not have been optimized in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…This is because addition of docetaxel to cisplatin and 5-fluorouracil therapy was shown to improve the outcomes of unresectable or recurrent gastric cancer patients [5], although it is not widely accepted as the standard treatment because of its severe toxicity. In Japan, several phase I and phase II trials evaluating combination treatment with docetaxel, cisplatin, and S-1 (DCS) of various regimens with modified doses and schedules for unresectable or recurrent gastric cancer patients have been conducted [6][7][8][9]. Although neutropenia and febrile neutropenia occurred frequently, the RR was quite high (76.1-87.7 %) in each trial.…”

Section: Introductionmentioning

confidence: 99%

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A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002

et al. 2016

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Background Gastric cancer with extensive lymph node metastasis is commonly considered unresectable, with a poor prognosis. We previously reported the results of the use of cisplatin and S-1 as preoperative chemotherapy for gastric cancer with extensive lymph node metastasis; docetaxel, cisplatin, and S-1 (DCS) have now been investigated for the same purpose. Methods Patients received two or three 28-day cycles of DCS therapy (docetaxel at 40 mg/m 2 and cisplatin at 60 mg/m 2 on day 1, S-1 at 40 mg/m 2 twice daily for 2 weeks) followed by gastrectomy with D2 plus para-aortic nodal dissection. After R0 resection, S-1 chemotherapy was given for 1 year. The primary end point was the response rate (RR) to preoperative chemotherapy determined by central peer review according to the Response Evaluation Criteria in Solid Tumors version 1.0. The planned sample size was 50, with one-sided alpha of 10 %, power of 80 %, expected RR of 80 %, and threshold of 65 %. Results Between July 2011 and May 2013, 53 patients were enrolled, of whom 52 were eligible. The clinical RR was 57.7 % [30/52, 80 % confidence interval 47.9-67.1 %, p = 0.89], and R0 resection was achieved in 84.6 % of patients (44/52). Common grade 3 or grade 4 adverse events during DCS therapy were leukocytopenia (18.9 %), neutropenia (39.6 %), and hyponatremia (15.1 %). The common grade 3 or grade 4 surgical morbidity was abdominal infection (10.2 %). The pathological RR was 50.0 % (26/52). Conclusions Preoperative DCS therapy was feasible but did not show a sufficient RR. Preoperative cisplatin and S-1 therapy is still considered the tentative standard treatment for this population until survival results are known.

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Section: Discussioncontrasting

confidence: 43%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002

et al. 2016

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“…An updated analysis presented at ESMO 2012 showed an improved median survival time of 12.5 months in the combination therapy group compared to 10.8 months in patients who received S-1 alone (p = 0.0319) [47]. Another Japanese approach involving a triplet regimen was evaluated in a phase I/II trial in which patients received S-1, docetaxel (40 mg/m 2 on day 1), and cisplatin (60 mg/m 2 on day 1) (DCS), or S-1 (80-120 mg/ day), 2 weeks on, 2 weeks off, every 4 weeks [48]. The most commonly observed grade 3/4 toxicity was neutropenia in 70 % of patients.…”

Section: Docetaxel-containing Triplet Combinationsmentioning

confidence: 99%

Optimal chemotherapy for advanced gastric cancer: is there a global consensus?

et al. 2013

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Chemotherapy for advanced gastric cancer

Wagner

Syn

Moehler

et al. 2017

Cochrane Database of Systematic Reviews

783

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Chemotherapy improves survival (by an additional 6.7 months) in comparison to BSC, and combination chemotherapy improves survival (by an additional month) compared to single-agent 5-FU. Testing all patients for HER-2 status may help to identify patients with HER-2-positive tumours, for whom, in the absence of contraindications, trastuzumab in combination with capecitabine or 5-FU in combination with cisplatin has been shown to be beneficial. For HER-2 negative people, all different two-and three-drug combinations including irinotecan, docetaxel, oxaliplatin or oral 5-FU prodrugs are valid treatment options for advanced gastric cancer, and consideration of the side effects of each regimen is essential in the treatment decision. Irinotecan-containing combinations and docetaxel-containing combinations (in which docetaxel was added to a single-agent or two-drug (platinum/5-FUcombination) show significant survival benefits in the comparisons studied above. Furthermore, docetaxel-containing three-drug regimens have increased response rates, but the advantages of the docetaxel-containing three-drug combinations (DCF, FLO-T) are counterbalanced by increased toxicity. Additionally, oxaliplatin-containing regimens demonstrated a benefit in OS as compared to the same regimen containing cisplatin, and there is a modest survival improvement of S-1 compared to 5-FU-containing regimens.Whether the survival benefit for three-drug combinations including cisplatin, 5-FU, and epirubicin as compared to the same regimen without epirubicin is still valid when second-line therapy is routinely administered and when cisplatin is replaced by oxaliplatin and 5-FU by capecitabine is questionable. Furthermore, the magnitude of the observed survival benefits for the three-drug regimens is not large enough to be clinically meaningful as defined recently by the American Society for Clinical Oncology (Ellis 2014). In contrast to the comparisons in which a survival benefit was observed by adding a third drug to a two-drug regimen at the cost of increased toxicity, the comparison of regimens in which another chemotherapy was replaced by irinotecan was associated with a survival benefit (of borderline statistical significance), but without increased toxicity. For this reason irinotecan/5-FU-containing combinations are an attractive option for first-line treatment. Although they need to be interpreted with caution, subgroup analyses of one study suggest that elderly people have a greater benefit form oxaliplatin, as compared to cisplatin-based regimens, and that people with locally advanced disease or younger than 65 years might benefit more from a three-drug regimen including 5-FU, docetaxel, and oxaliplatin as compared to a two-drug combination of 5-FU and oxaliplatin, a hypothesis that needs further confirmation. For people with good performance status, the benefit of second-line chemotherapy has been established in several RCTs.

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A multicenter phase II study of combined chemotherapy with docetaxel, cisplatin, and S-1 in patients with unresectable or recurrent gastric cancer (KDOG 0601)

Abstract: Triplet of docetaxel, cisplatin, and S-1 is a well-tolerated and highly active regimen for advanced or recurrent gastric cancer. A 60 mg/m(2) of cisplatin is as effective as 70 mg/m(2) of cisplatin.

Cited by 68 publications

References 12 publications

A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002

A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002

Optimal chemotherapy for advanced gastric cancer: is there a global consensus?

Chemotherapy for advanced gastric cancer

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