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International Journal of Clinical Oncology

Erschienen in:

08.08.2023 | Original Article

Effect of duration of adjuvant chemotherapy with S-1 (6 versus 12 months) for resected pancreatic cancer: the multicenter clinical randomized phase II postoperative adjuvant chemotherapy S-1 (PACS-1) trial

verfasst von: Hiroto Kayashima, Shinji Itoh, Mototsugu Shimokawa, Hiromitsu Hayashi, Hiroshi Takamori, Kengo Fukuzawa, Mizuki Ninomiya, Kenichiro Araki, Yo-ichi Yamashita, Keishi Sugimachi, Hideaki Uchiyama, Yuji Morine, Tohru Utsunomiya, Tadashi Uwagawa, Takashi Maeda, Hideo Baba, Tomoharu Yoshizumi

Erschienen in: International Journal of Clinical Oncology | Ausgabe 11/2023

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Abstract

Background

Six-month adjuvant chemotherapy with S-1 is standard care for resected pancreatic cancer in Japan; however, the optimal duration has not been established. We aimed to evaluate the impact of duration of adjuvant chemotherapy with S-1.

Methods

We performed a multicenter, randomized, open-label, phase II study. Patients with histologically proven invasive pancreatic ductal carcinoma, pathological stage I–III, and no local residual or microscopic residual tumor were eligible. Patients were randomized 1:1 to receive 6- or 12-month adjuvant chemotherapy with S-1. The primary endpoint was 2-year overall survival (OS). Secondary endpoints were disease-free survival (DFS) and feasibility.

Results

A total of 170 patients were randomized (85 per group); the full analysis set was 82 in both groups. Completion rates were 64.7% (6-month group) and 44.0% (12-month group). Two-year OS was 71.5% (6-month group) and 65.4% (12-month group) (hazard ratio (HR): 1.143; 80% confidence interval CI 0.841–1.553; P = 0.5758). Two-year DFS was 46.4% (6-month group) and 44.9% (12-month group) (HR: 1.069; 95% CI 0.727–1.572; P = 0.6448). In patients who completed the regimen, 2-year DFS was 56.5% (6-month group) and 75.0% (12-month group) (HR: 0.586; 95% CI 0.310–1.105; P = 0.0944). Frequent (≥ 5%) grade ≥ 3 adverse events comprised anorexia (10.5% in the 6-month group) and diarrhea (5.3% vs. 5.1%; 6- vs. 12-month group, respectively).

Conclusions

In patients with resected pancreatic cancer, 12-month adjuvant chemotherapy with S-1 was not superior to 6-month therapy regarding OS and DFS.

Kobayashi K, Einama T, Takihata Y et al (2022) Therapeutic efficacy of dose-reduced adjuvant chemotherapy with S-1 in patients with pancreatic cancer: a retrospective study. BMC Cancer 22:1028CrossRefPubMedPubMedCentral

Itoh S, Tsujita E, Fukuzawa K et al (2021) Prognostic significance of preoperative PNI and CA19-9 for pancreatic ductal adenocarcinoma: a multi-institutional retrospective study. Pancreatology 21:1356–1363CrossRefPubMed

Sultana A, Smith CT, Cunningham D et al (2007) Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses. J Clin Oncol 25:2607–2615CrossRefPubMed

Sperti C, Pasquali C, Piccoli A et al (1997) Recurrence after resection for ductal adenocarcinoma of the pancreas. World J Surg 21:195–200CrossRefPubMed

Klinkenbijl JH, Jeekel J, Sahmoud T et al (1999) Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 230:776–782CrossRefPubMedPubMedCentral

Neoptolemos JP, Stocken DD, Friess H et al (2004) A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350:1200–1210CrossRefPubMed

Oettle H, Post S, Neuhaus P et al (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297:267–277CrossRefPubMed

Conroy T, Hammel P, Hebbar M et al (2018) FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med 379:2395–2406CrossRefPubMed

Uesaka K, Boku N, Fukutomi A et al (2016) Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet 388:248–257CrossRefPubMed

10.

Sakuramoto S, Sasako M, Yamaguchi T et al (2007) Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357:1810–1820CrossRefPubMed

11.

Yoshikawa T, Terashima M, Mizusawa J et al (2019) Four courses versus eight courses of adjuvant S-1 for patients with stage II gastric cancer (JCOG1104 [OPAS-1]): an open-label, phase 3, non-inferiority, randomized trial. Lancet Gastroenterol Hepatol 4:208–216CrossRefPubMed

12.

Japanese Pancreas Society (2009) General rules for the study of pancreatic cancer, 6th edn. Kanehara, Tokyo

13.

Sobin LH, Gospodarowicz MK, Wittekind C (2009) TNM classification of malignant tumours, 7th edn. Wiley-Blackwell, Hoboken

14.

Oken MM, Creech RH, Tormey DC et al (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649–655CrossRefPubMed

15.

Common Terminology Criteria for Adverse Events v4.0 (CTCAE). http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40

16.

Tomimaru Y, Eguchi H, Inoue Y et al (2023) Impact of S-1 adjuvant chemotherapy longer than 6 months on survival in patients with resected pancreatic cancer: a nationwide survey by the Japan Pancreas Society based on real-world data. Cancer 129:728–739CrossRefPubMed

17.

Valle JW, Palmer D, Jackson R et al (2014) Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. J Clin Oncol 32:504–512CrossRefPubMed

18.

Yabusaki N, Fujii T, Yamada S et al (2016) The significance of relative dose intensity in adjuvant chemotherapy of pancreatic ductal adenocarcinoma including the analysis of clinicopathological factors influencing relative dose intensity. Medicine (Baltimore) 95:e4282CrossRefPubMed

19.

Tsukuda M, Kida A, Fujii M et al (2005) Randomized scheduling feasibility study of S-1 for adjuvant chemotherapy in advanced head and neck cancer. Br J Cancer 93:884–889CrossRefPubMedPubMedCentral

20.

Arai W, Hosoya Y, Hyodo M et al (2004) Alternate-day oral therapy with TS-1 for advanced gastric cancer. Int J Clin Oncol 9:143–148CrossRefPubMed

21.

Rino Y, Takanashi Y, Yukawa N et al (2006) A phase I study of bi-weekly combination therapy with S-1 and docetaxel for advanced or recurrent gastric cancer. Anticancer Res 26:1455–1462PubMed

22.

Okumura N, Soh J, Suzuki H et al (2021) Randomized phase II study of daily and alternate-day administration of S-1 for adjuvant chemotherapy in completely-resected stage I non-small cell lung cancer: results of the Setouchi Lung Cancer Group Study 1301. BMC Cancer 21:506CrossRefPubMedPubMedCentral

23.

Moriwaki T, Sakai Y, Ishida H et al (2019) Phase II study of S-1 on alternate days plus bevacizumab in patients aged ≥ 75 years with metastatic colorectal cancer (J-SAVER). Int J Clin Oncol 24:1214–1222CrossRefPubMed

24.

Ojima T, Nakamura M, Nakamori M et al (2019) Triplet chemotherapy with docetaxel, cisplatin and S-1 for unresectable advanced squamous cell carcinoma of the esophagus: phase I/II trial results. Oncotarget 10:847–855CrossRefPubMedPubMedCentral

25.

Motoi F, Kosuge T, Ueno H et al (2019) Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05). Jpn J Clin Oncol 49:190–194CrossRefPubMed

Titel: Effect of duration of adjuvant chemotherapy with S-1 (6 versus 12 months) for resected pancreatic cancer: the multicenter clinical randomized phase II postoperative adjuvant chemotherapy S-1 (PACS-1) trial
verfasst von: Hiroto Kayashima
Shinji Itoh
Mototsugu Shimokawa
Hiromitsu Hayashi
Hiroshi Takamori
Kengo Fukuzawa
Mizuki Ninomiya
Kenichiro Araki
Yo-ichi Yamashita
Keishi Sugimachi
Hideaki Uchiyama
Yuji Morine
Tohru Utsunomiya
Tadashi Uwagawa
Takashi Maeda
Hideo Baba
Tomoharu Yoshizumi
Publikationsdatum: 08.08.2023
Verlag: Springer Nature Singapore
Erschienen in: International Journal of Clinical Oncology / Ausgabe 11/2023
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-023-02399-7

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Effect of duration of adjuvant chemotherapy with S-1 (6 versus 12 months) for resected pancreatic cancer: the multicenter clinical randomized phase II postoperative adjuvant chemotherapy S-1 (PACS-1) trial