Safety and efficacy of S-IROX (S-1, irinotecan and oxaliplatin combination therapy) in patients with advanced pancreatic cancer: A multicenter phase 1b dose-escalation and dose-expansion clinical trial

Ohba, Akihiro; Ueno, Hideki; Shiba, Satoshi; Okano, Naohiro; Kobayashi, Takaaki; Nagashima, Fumio; Sasahira, Naoki; Sasaki, Mitsuhito; Imaoka, Hiroshi; Sakamoto, Yasunari; Kondo, Shunsuke; Morizane, Chigusa; Ozaka, Masato; Ikeda, Masafumi; Furuse, Junji; Okusaka, Takuji

doi:10.1016/j.ejca.2022.06.010

Cited by 6 publications

(7 citation statements)

References 21 publications

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“…Diarrhea and neutropenia, including a few G3 cases, were observed at both level-0 and -1 doses. These AEs were consistently reported in the phase I first-line S-IROX study and retrospective second-line S-IROX study (diarrhea [47.4%-56%] and neutropenia [63.2%-87%]) 13,17 . Additionally, G3-4 neutropenia (26.3%-44%) and diarrhea (11%-26.3%) were observed in these previous studies.…”

Section: Discussionmentioning

confidence: 61%

“…In our study, the RD for the second-line S-IROX regimen was confirmed to be level-1 (80 mg/m2 S-1, 85 mg/m2 oxaliplatin, and 150 mg/m2 irinotecan) based on this definition. The phase-1 firstline S-IROX study also set the RD at the same dosage as in our study due to its toxicity 17 . Given that our study involved patients who had already received first-line GnP chemotherapy and were unable to receive FOLFIRINOX due to age or general condition, the level-1 dosage appears to have sufficient therapeutic intensity.…”

Section: Discussionmentioning

confidence: 99%

“…Oxaliplatin was administered intravenously over 2 h, followed by intravenous administration of irinotecan over 2 h. S-1 was given orally twice daily on days 1-7 (Supplemental Fig. 1) 17 . Aprepitant (125 mg on day 1 and 80 mg on days 2-3) was also administered as an antiemetic.…”

Section: Study Design and Treatmentmentioning

confidence: 99%

“…To consider patient condition after GnP therapy, the doses of irinotecan were defined as follows: level-0, 120 mg/m 2 ; and level-1, 150 mg/m 2 (original dose). Because the RD of irinotecan was confirmed as 150 mg/m 2 in an original regimen of first-line S-IROX and SOXIRI 15,17 , and patient general condition potentially deteriorated in second-line therapy, this phase I study for the second-line treatment was evaluated up to the RD of the original regimens (irinotecan: 150 mg/m 2 ). The protocol was repeated until tumor progression, the development of DLTs, or the patient declined to continue.…”

Section: Study Design and Treatmentmentioning

confidence: 99%

“…Recently, the combination of S-1, an oral fluoropyrimidine widely used for PC in Japan 11,12 , with irinotecan and oxaliplatin, S-IROX or SOXIRI, has been investigated. These regimens are potentially safer and more effective than FOLFIRINOX [13][14][15][16][17] . This study aimed to determine the recommended second-line dose (RD) of S-IROX after GnP failure in patients with unresectable PC.…”

Section: Introductionmentioning

confidence: 99%

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A phase-I study of second-line S-IROX for unresectable pancreatic cancer after gemcitabine plus nab-paclitaxel failure

Okuno,

Mukai,

Iwata

et al. 2024

Preprint

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Background and aims: Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX are widely used as first-line regimens for unresectable pancreatic cancer (PC). When GnP therapy is selected, considering patient age or condition, second-line FOLFIRINOX is sometimes difficult to administer owing to its toxicity. This study aimed to determine the recommended dose (RD) of S-IROX (S-1, oxaliplatin, and irinotecan combination) regimens in patients with unresectable PC after first-line GnP failure. Methods: This phase-I study used the “3+3” dose-escalation design with two dose levels. Patients who failed first-line GnP therapy for unresectable PC were enrolled. Oxaliplatin and irinotecan were administered on day 1, and S-1 was administered orally twice daily on days 1–7, followed by 7 days of rest. The primary endpoints were dose-limiting toxicities (DLTs) and determination of RD. The secondary endpoint was the evaluation of potential antitumor activity. Results: Nine patients received the second-line S-IROX regimen. In level-0 (S-1, 80mg/m2; oxaliplatin, 85mg/m2; and irinotecan, 120mg/m2), no patient experienced DLT; however, one patient experienced grade 3 neutropenia. At level-1 (irinotecan increased to 150mg/m2), one of six patients experienced DLTs, including G3 diarrhea. The RD was confirmed at the level-1 dose. The response rate, disease control rate, median progression-free survival, and median overall survival were 33.3%, 77.8%, 172 (range:77–422) days, and 414 (101–685) days, respectively. One patient underwent surgery after the second-line S-IROX therapy. Conclusions: Second-line S-IROX treatment was deemed acceptable. The RD was set at level-1 dose (S-1, 80mg/m2; oxaliplatin, 85mg/m2; and irinotecan, 150mg/m2).

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Study Design and Treatmentmentioning

confidence: 99%

Section: Study Design and Treatmentmentioning

confidence: 99%