A Prospective, Open-Label, Multicenter Phase 2 Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma

Eguchi, Hidetoshi; Takeda, Yutaka; Takahashi, Hidenori; Nakahira, Shin; Kitajima, Masaki; Shimizu, Junzo; Sakai, Daisuke; Isohashi, Fumiaki; Nagano, Hiroaki; Mori, Masaki; Doki, Yuichiro

doi:10.1245/s10434-019-07735-8

Cited by 42 publications

(63 citation statements)

References 29 publications

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“…The duration of neoadjuvant was about 2 months in most previously reported trials for R PDAC . A longer course of neoadjuvant might improve the survival outcome when the regimen continues to be active after the initial treatment period of 2 months.…”

Section: Optimal Duration For Neoadjuvantmentioning

confidence: 99%

“…Excluding non‐responders and also vulnerable cases, the addition of effective treatment would have a good effect on tumor control. Compared to other types of cancer that are chemotherapy‐ or radiotherapy‐sensitive, pathological complete response (CR) is rarely obtained after neoadjuvant for PDAC . Though two cycles of NAC‐GS showed significant survival benefit for potentially resectable PDAC, it might not be of sufficient duration for a large proportion of PDAC patients because of its poor prognosis.…”

Section: Optimal Duration For Neoadjuvantmentioning

confidence: 99%

“…18,19 Landry et al 20 These results are summarized in Table 1. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Although these studies reported the survival outcome of an ITT cohort, none of them had a cohort treated by upfront surgery as a control. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Several meta-analyses investigated the efficacy of neoadjuvant.…”

Section: Pros Pec Tive S Tud Ie S and Me Ta-analys E Smentioning

confidence: 99%

“…Many prospective non-randomized trials of NACRT have been reported. 14,15,[18][19][20][21][22]25,27,28 RCTs comparing NACRT with upfront surgery, however, have not yet been fully reported, [33][34][35][36][37] in contrast to NAC. [38][39][40] The good survival outcomes.…”

Section: Chemother Apy And/or R Adiother Apy ?mentioning

confidence: 99%

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Neoadjuvant treatment for resectable pancreatic adenocarcinoma: What is the best protocol?

Motoi

Unno

2020

Annals of Gastroent Surgery

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Although upfront surgery has been the gold standard for pancreatic adenocarcinoma that is planned for resection, it should be compared with the alternative strategy of neoadjuvant therapy. Despite the many reports of the efficacy of neoadjuvant therapy, most of them were not comparative. Recently Prep‐02/JSAP05 study clearly demonstrated the significant survival benefit of neoadjuvant chemotherapy over upfront surgery for pancreatic adenocarcinoma that is planned for resection. These findings opened a new chapter of neoadjuvant therapy. Ongoing trials are expected to confirm the evidence. This review summarizes the past, present, and future perspectives of neoadjuvant therapy and its optimization.

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Section: Optimal Duration For Neoadjuvantmentioning

confidence: 99%

Section: Optimal Duration For Neoadjuvantmentioning

confidence: 99%

Section: Pros Pec Tive S Tud Ie S and Me Ta-analys E Smentioning

confidence: 99%

Section: Chemother Apy And/or R Adiother Apy ?mentioning

confidence: 99%

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Neoadjuvant treatment for resectable pancreatic adenocarcinoma: What is the best protocol?

Motoi

Unno

2020

Annals of Gastroent Surgery

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“…3,4 The report entitled ''A Prospective, Open-Label Multicenter Phase II Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent With Radiation for Resectable Pancreatic Ductal Adenocarcinoma'' described the role of neoadjuvant radiation (total dose, 50.4 Gy) given concurrently with full doses of chemotherapy (gemcitabine and S1). 5 The authors demonstrated an impressive median survival of 55 months for 63 patients who had resectable and borderline resectable tumors treated with this regimen. 5 This trial adds to the body of knowledge regarding the use of neoadjuvant chemoradiation in the treatment of pancreatic cancer.…”

mentioning

confidence: 95%

Editorial About: “A Prospective, Open-Label, Multicenter Phase II Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma”

2019

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Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease that affected approximately 53,000 new patients in 2016. Patients with a diagnosis of this malignancy have a 5-year overall survival rate of 10%, which increases only to 25% for those with resectable disease. 1,2 These poor outcomes reflect two notions. First, PDAC is a systemic disease at the time of diagnosis regardless of clinical stage. As such, treatment must include systemic therapy as one component of the therapy. Second, despite progressive advances during the last several years, current treatment options have limited efficacy at reducing recurrences and disease progression.Historically, results from studies evaluating the use of radiotherapy for PDAC have been mixed, with adjuvant radiotherapy trials showing disparate results. 3,4 The report entitled ''A Prospective, Open-Label Multicenter Phase II Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent With Radiation for Resectable Pancreatic Ductal Adenocarcinoma'' described the role of neoadjuvant radiation (total dose, 50.4 Gy) given concurrently with full doses of chemotherapy (gemcitabine and S1). 5 The authors demonstrated an impressive median survival of 55 months for 63 patients who had resectable and borderline resectable tumors treated with this regimen. 5 This trial adds to the body of knowledge regarding the use of neoadjuvant chemoradiation in the treatment of pancreatic cancer. The unique aspect of this trial was full doses of chemotherapy delivered concurrently with radiation, thus targeting both local and distant disease.The results of this study should be taken in light of other recent trials. The PREOPANC-1 trial was a phase 3 trial that evaluated the role of preoperative chemoradiotherapy versus immediate surgery for 246 patients with resectable or borderline resectable tumors. 6 All the patients received 6 months of perioperative gemcitabine. Despite equal total doses of systemic chemotherapy, the trial demonstrated improvements in both median recurrencefree survival [median, 9.9 vs 7.7 months; hazard ratio (HR), 0.67; p = 0.010] and overall survival (median, 17.1 vs 13.5 months; HR, 0.71; p = 0.047) with the neoadjuvant chemoradiation approach. It is important to note that the patients in the chemoradiation arm of the study received 30% of all the systemic chemotherapy during the preoperative period. Moreover, this trial did not use the more active systemic regimens available currently.The randomized phase 2 and 3 Prep-02/JSAP-05 trial, which used the same chemotherapy regimen in the experimental arm as the current study used, compared the use of neoadjuvant chemotherapy with the use of upfront surgery followed by adjuvant S-1 chemotherapy. 7 The study demonstrated a significantly improved median overall survival of 36.7 months in the neoadjuvant therapy cohort versus 26.7 months in the upfront surgery cohort (p = 0.015), with a 2-year overall survival rate of 64% versus 53%. Therefore, the single-arm design of the current study begs the question re...

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The outcome of a multidisciplinary approach incorporating neoadjuvant chemoradiotherapy with S1 for resectable pancreatic ductal adenocarcinoma

Matsumura

Honda

Tani

et al. 2022

Annals of Gastroent Surgery

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Aim This study was performed to evaluate the efficacy of a multidisciplinary approach incorporating neoadjuvant chemoradiotherapy with S1 (S1‐NACRT) for resectable pancreatic ductal adenocarcinoma. Methods The medical records of 132 patients who received S1‐NACRT for resectable pancreatic ductal adenocarcinoma from 2010 to 2019 were reviewed. The S1‐NACRT regimen consisted of S1 at a dose of 80‐120 mg/body/day together with 1.8 Gy of radiation in 28 fractions. The patients were re‐evaluated 4 weeks after S1‐NACRT completion, and a pancreatectomy was then considered. Results Adverse events of S1‐NACRT ≥grade 3 occurred in 22.7% of the patients, and 1.5% discontinued therapy. Of the 112 patients who underwent a pancreatectomy, 109 underwent R0 resection. Adjuvant chemotherapy with relative dose intensity ≥50% was administered to 74.1% of the patients who underwent resection. The median overall survival of all patients was 47 months, and the median overall survival and recurrence‐free survival of patients who underwent resection was 71 and 32 months, respectively. According to the multivariate analyses of prognostic factors for overall survival in patients who underwent resection, negative margin status (hazard ratio: 0.182; P = 0.006) and relative dose intensity of adjuvant chemotherapy ≥50% (hazard ratio 0.294; P < 0.001) were independent prognostic factors of overall survival. Conclusions A multidisciplinary approach incorporating S1‐NACRT for resectable pancreatic ductal adenocarcinoma demonstrated acceptable tolerability and good local control and resulted in comparable survival benefits.

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A Prospective, Open-Label, Multicenter Phase 2 Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma

Cited by 42 publications

References 29 publications

Neoadjuvant treatment for resectable pancreatic adenocarcinoma: What is the best protocol?

Neoadjuvant treatment for resectable pancreatic adenocarcinoma: What is the best protocol?

Editorial About: “A Prospective, Open-Label, Multicenter Phase II Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma”

The outcome of a multidisciplinary approach incorporating neoadjuvant chemoradiotherapy with S1 for resectable pancreatic ductal adenocarcinoma

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