A Phase II Trial of Neoadjuvant Preoperative Chemoradiotherapy With S-1 Plus Irinotecan and Radiation in Patients With Locally Advanced Rectal Cancer: Clinical Feasibility and Response Rate

Sato, Takeo; Ozawa, Heita; Hatate, Kazuhiko; Onosato, Wataru; Naito, Masanori; Nakamura, Takatoshi; Ihara, Atsushi; Koizumi, Wasaburo; Hayakawa, Kazushige; Okayasu, Isao; Yamashita, Keishi; Watanabe, Masahiko

doi:10.1016/j.ijrobp.2009.11.007

Cited by 55 publications

(58 citation statements)

References 23 publications

(24 reference statements)

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“…In this regard, there is legitimate concern that the combination of two drugs in preoperative CRT is not always sufficient to control locoregional lesions and eradicate distant metastases over fluoropyrimidine. On the other hand, Sato et al [22] reported about a phase II trial of preoperative CRT with S-1 plus irinotecan and showed that this regimen had high pathological CR rate of 37.3%.…”

Section: Discussionmentioning

confidence: 99%

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A Phase II Trial of Preoperative Chemoradiotherapy with Oral DPD-Inhibitory Fluoropyrimidines in Patients with Advanced Rectal Cancer

Hotchi¹,

Okitsu²,

Miura³

et al. 2012

JCT

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Background: Preoperative chemoradiotherapy (CRT) with 5-FU has been widely used to improve local control of disease and to preserve anal sphincter in the treatment of rectal cancer. UFT and S-1 as oral dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidines enhance the therapeutic effect of 5-FU by modulating its metabolic pathways. The purpose of this study was to evaluate the efficacy and toxicity of CRT using UFT versus S-1 in patients with locally advanced rectal cancer. Methods: Fifty-nine patients who received preoperative CRT (40 Gy radiotherapy) were randomly assigned to either UFT or S-1 groups. UFT and S-1 were administered during the radiotherapy course. Response to CRT was determined using a histopathologic examination and RECIST of surgically resected specimens and classified as responders (CR, PR and Grade 2, 3) or nonresponders (SD, PD and Grade 0, 1). Results: All patients were randomly allocated to S-1 group (n = 30) or UFT group (n = 29). Pathological response rate (Grade 2 and Grade 3) was 57% in the S-1 group and 45% in the UFT group (p = 0.36). Pathological complete response (CR) rate (Grade3) was 7% in the S-1 group and 4% in the UFT group (p = 0.98). There was no statistically significant difference between the two groups in regard to the response rate of RECIST (p = 0.52). There was no statistically significant difference between the groups based on the downstaging rate, resection of tumor, sphincter preservation and marginal invasion. The incidence of Grade 3 diarrhea was significantly more frequent in the S-1 group (7%) compared with the UFT group (0%) (p = 0.02). Conclusion: The results supported the conclusion that CRT using UFT or S-1 is effective and feasible for patients with locally advanced rectal cancer.

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Section: Discussionmentioning

confidence: 99%

“…A part of this study was presented in Gastrointestinal Cancer Symposium, San Francisco, CA, USA (Jan. [20][21][22] 2011).…”

Section: Acknowledgementsmentioning

confidence: 99%

A Phase II Trial of Preoperative Chemoradiotherapy with Oral DPD-Inhibitory Fluoropyrimidines in Patients with Advanced Rectal Cancer

Hotchi¹,

Okitsu²,

Miura³

et al. 2012

JCT

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“…The protocol of NA-CRT applied for the present study with minor modifications was recently described in detail (13). Briefly, all the patients were placed in the supine position and helically scanned on an Aquilion LB CT unit (Toshiba, Otawara-shi, Japan).…”

Section: Patientsmentioning

confidence: 99%

“…Clinical studies of irinotecan (CPT-11) plus S-1 combination therapy have been reported to produce non-inferiority outcomes for metastatic colorectal cancer. In addition, several clinical studies have demonstrated that NA-RT combined with S-1 is associated with mild toxicity and an efficacy equivalent to that achieved by other systemic chemotherapies (13).…”

Section: Introductionmentioning

confidence: 97%

Diffusion-weighted magnetic resonance imaging for prediction of tumor response to neoadjuvant chemoradiotherapy using irinotecan plus S-1 for rectal cancer

Doi

Beppu

Kato

et al. 2015

Molecular and Clinical Oncology

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Abstract. The purpose of this study was to investigate the clinical value of diffusion-weighted (DW) magnetic resonance imaging (MRI) as a predictor of tumor response in patients receiving neoadjuvant chemoradiotherapy (NA-CRT) for rectal cancer (RC) through measurement of the apparent diffusion coefficient (ADC) value in each tumor. Neoadjuvant radiotherapy with a total dose of 45 Gy in 25 fractions was performed in all 16 patients with RC, combined with irinotecan and S-1. MRI was performed before and after NA-CRT. Multiple factors were assessed to predict the pathological response to NA-CRT. The pathological response rate was determined in 9 patients (56.3%). Statistical analyses indicated that the ADC value prior to NA-CRT was significantly lower in patients with a better response to NA-CRT (P= 0.023). A cut-off value of 0.750x10 -3 mm 2 /sec obtained by a receiver operating characteristic curve analysis indicated a sensitivity of 77.8% and specificity of 85.7% for pathological responders to NA-CRT. In addition, the patients with lower ADC values exhibited a greater pathological response to NA-CRT (P= 0.041). In conclusion, the ADC value of MRI of RC patients treated with NA-CRT followed by surgery may provide valuable information to predict the response to NA-CRT.

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“…However, disease recurrence remains the major cause of mortality in these patients and recent efforts, involving the incorporation of newer cytotoxic or molecular-targeted agents into chemoradiotherapy regimens, have been reported to improve oncological outcome. The addition of oxaliplatin or irinotecan to 5-FU administered concurrently with radiotherapy, resulted in a more favorable pathological response in certain phase I/II trials (5,6), while the addition of other chemotherapeutic drugs significantly increased toxicity or exhibited no oncological improvement (7,8). Similarly, incorporating anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor therapies into preoperative chemoradiotherapy in patients with locally advanced rectal cancer did not significantly enhance pathological downstaging, although few randomized trials have been undertaken (9).…”

Section: Introductionmentioning

confidence: 99%

Phase I study of 5-fluorouracil, leucovorin and bevacizumab in combination with radiation therapy in patients with locally advanced rectal cancer

Inoue

Okigami

Kawamoto

et al. 2013

Molecular and Clinical Oncology

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Abstract.A phase I clinical study was conducted to determine the maximum tolerated dose (MTD) and recommended dose (RD) of the standard treatment of 5-fluorouracil/l-leucovorin (5-FU/LV) with bevacizumab, in combination with radiation therapy in patients with locally advanced rectal cancer. Eligible patients had previously untreated stage T3 or T4 locally advanced rectal cancer. Patients received radiotherapy to the pelvis, at a total dose of 45 Gy in 25 fractions. During radiotherapy, patients received three courses of a simplified LV and 5-FU regimen (sLV5FU2), in combination with bevacizumab. Bevacizumab was infused at a fixed dose of 5 mg/ kg on Days 1, 15 and 29. The sLV5FU2 regimen consisted of 200 mg/m 2 of LV administered by continuous intravenous (i.v.) infusion over 2 h, followed by 400 mg̸m 2 of 5-FU administered by i.v. bolus injection, delivered at an initial loading dose of 2,000 mg/m 2 over 46 h. The dose was gradually increased to determine the MTD and RD of this regimen. Of the patients enrolled in the study, two developed Grade 3 diarrhea and one developed Grade 3 neutropenia. Since dose-limiting toxicity (DLT) occurred in two out of the six patients, 5-FU at a dose of 2,000 mg/m 2 over 46 h was determined as the MTD and designated as the RD, taking into consideration the toxicities in matched patients who received standard preoperative chemoradiotherapy with sLV5FU2 during the same period. The combination of 5-FU, LV, bevacizumab and radiotherapy in patients with locally advanced rectal cancer was found to be tolerable, with encouraging response rates. Further investigation is required in a phase II setting.

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A Phase II Trial of Neoadjuvant Preoperative Chemoradiotherapy With S-1 Plus Irinotecan and Radiation in Patients With Locally Advanced Rectal Cancer: Clinical Feasibility and Response Rate

Cited by 55 publications

References 23 publications

A Phase II Trial of Preoperative Chemoradiotherapy with Oral DPD-Inhibitory Fluoropyrimidines in Patients with Advanced Rectal Cancer

A Phase II Trial of Preoperative Chemoradiotherapy with Oral DPD-Inhibitory Fluoropyrimidines in Patients with Advanced Rectal Cancer

Diffusion-weighted magnetic resonance imaging for prediction of tumor response to neoadjuvant chemoradiotherapy using irinotecan plus S-1 for rectal cancer

Phase I study of 5-fluorouracil, leucovorin and bevacizumab in combination with radiation therapy in patients with locally advanced rectal cancer

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