The comparison of mFOLFOXIRI with CAOX/SOX as neoadjuvant chemotherapy for locally advanced rectal cancer.

51 Background: The standard therapy for the locally advanced rectal cancer (LARC) (Ra or Rb, T2Npsitive, T3/4Nany) is chemoradiotherapy (CRT) followed by surgery. The CRT prevents local recurrence, although problems such as complications or the improvement of distant recurrence still remain. Several studies about the neoadjuvant chemotherapy (NAC) without radiation showed favorable R0 resection rate and outcome, however the best regimen of NAC is unclear. The aim of this study is to investigate the efficacy and safety of mFOLFOXIRI and CAPOX/SOX as NAC. Methods: We examined the patients (pts) with LARC who were planned to receive mFOLFOXIRI (5FU 2400mg/m2/day1-2, leucovorin 200mg/m2, oxaliplatin 85mg/m2, irinotecan 150mg/m2, every 2 weeks) or CAPOX/SOX(capecitabine 2000mg/m2 or S-1 mg/m2 80day1-14, oxaliplatin 130mg/m2, day1, every 3weeks) for 8-12 weeks as NAC, retrospectively. Results: Forty-nine pts received mFOLFOXIRI and thirty-two pts received XELOX/SOX between Jan 2015 and Mar 2019. The characteristics of mFOLFOXIRI and XELOX/SOX were as follows; median age, 64 (37-80) and 65 (33-68); PS 0/1, 46(94%)/3(6%) and 14(44%)/18(56%); Ra/Rb-P, 4(8%)/45(92%) and 0/32; clinical T2/3/4, 4(7%)/27(55%)/19(39%) and 1(3%)/18(56%)/13(41%); clinical N0/1/2, 13(27%)/26(53%)/10(20%) and 7(22%)/17(53%)/8(25%). The pathological response rate which was defined as tumor affected area over one-third were 61.2% in mFOLFOXIRI and 65.6% in CAPOX/SOX including complete remission of 4.1% and 12.5%, respectively. Six of 49 pts withdrew from mFOLFOXIRI due to toxicities, whereas one of 32 pts from CAPOX/SOX. One pt received CRT after SOX because of lack of efficacy. The major grade 3/4 toxicities of mFOLFOXIRI were neutropenia (n = 22, 45%), thrombocytopenia and febrile neutropenia (n = 4, 8%) and anorexia (n = 3, 6%), whereas CAPOX/SOX neutropenia (n = 3. 9%), thrombocytopenia (n = 1, 3%) and hand-foot syndrome (n = 1, 3%). The one year of relapse free survival rate were 85.4% and 83.6%. Conclusions: Although the pathological response of mFOLFOXIRI was comparable with CAPOX/SOX, CAPOX/SOX was less toxic.The further investigation including 5 year overall survival rate rate was needed.

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Neoadjuvant chemotherapy with modified FOLFOXIRI for locally advanced rectal cancer: A single center phase II trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.69 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 69-69

Author(s):

Wen Zhang ◽

Haitao Zhou ◽

Jun Jiang ◽

Yuelu Zhu ◽

Shuangmei Zou ◽

...

Keyword(s):

Rectal Cancer ◽

Neoadjuvant Chemotherapy ◽

Folinic Acid ◽

Phase Ii ◽

Phase Ii Trial ◽

Locally Advanced ◽

Venous Invasion ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

R0 Resection

69 Background: Chemoradiotherapy (CRT) remains the standard treatment choice for locally advanced rectal cancer (LARC). Neoadjuvant chemotherapy alone with doublet mFOLFOX6 (folinic acid, 5-fluorouracil, and oxaliplatin) seemed not to influence recurrence free survival with the advantage of less treatment-related complications. This phase II trial was designed to evaluate the efficacy and safety of neoadjuvant triplet chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in patients with LARC (NCT03443661). Methods: Patients with LARC received up to 5 cycles of mFOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2 were administered on Day 1, fluorouracil 2400 mg/m2 was administered as a continuous intravenous infusion for 48 hours on Day 1, and was repeated every 14 days). Magnetic resonance imaging (MRI) was performed to assess the baseline and post-chemotherapy TN stage. Radical resection was performed within 4–6 weeks of the last dose of chemotherapy if the tumor shrank or remained stable. Adjuvant chemotherapy with mFOLFOX6 or XELOX (oxaliplatin and capecitabine) was recommended. Postoperative radiation was planned for R1 resection, ypT4b, ypN2, and positive circumferential resection margin (CRM). The primary endpoint was the pathological complete response (pCR) rate. Results: Between December 2015 to March 2019, a total of 50 patients were enrolled. 48 (96%) of the patients were clinically node-positive, 28 (56.5%) were CRMnvolved, and 39 (78.4%) were extramural venous invasion (EMVI)-positive. The median cycle of neoadjuvant mFOLFOXIRI chemotherapy was 5 (range, 1–5). A total of 46/50 (92%) patients underwent total mesorectal excision (TME) surgery, all with R0 resection. The pCR rate was 4.3% (2/46). Twenty-three of 46 (50%) patients achieved pathological node-negative status. The proportion of pathologically positive CRM and EMVI were 2.2% and 34.7%, respectively (table). Adjuvant radiotherapy was given to 14/46 (30.4%) patients. The most common Grade 3 or more toxicities included neutrocytopenia (50%), leukopenia (14%), and diarrhea (12%) during neoadjuvant chemotherapy. Clinical meaningful surgical morbidities included pneumonia (n=1), pelvic infection (n=1), and anastomotic fistula (n=1). With a median follow-up time of 33 months (range, 14–73 months), local recurrences and distant metastases were confirmed in 3 (6.5%) and 8 (17.4%) cases, respectively. Conclusions: Neoadjuvant chemotherapy with mFOLFOXIRI yielded a significant down-staging effect with an ordinary pCR rate, and seemed effective in eliminating EMVI and transforming CRM-positive to CRM-negative status in patients with LARC. The preliminary survival results are promising. This regimen could serve as a potential alternative to CRT in selected patients with LARC. Clinical trial information: NCT03443661. [Table: see text]

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Neoadjuvant chemotherapy enables R0 resection of locally advanced rectal cancer in a patient with a previously irradiated pelvis

British Journal of Radiology ◽

10.1259/bjr/55455027 ◽

2007 ◽

Vol 80 (956) ◽

pp. e170-e172

Author(s):

P Sanghera ◽

K Ho ◽

T Muscroft ◽

A Hartley

Keyword(s):

Rectal Cancer ◽

Neoadjuvant Chemotherapy ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

R0 Resection ◽

Irradiated Pelvis

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Short- and long-term outcomes of neoadjuvant-synchronus S-1+radiotherapy for locally advanced rectal cancer: Multicenter phase II study.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.720 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 720-720

Author(s):

Takahiro Hiratsuka ◽

Tomonori Akagi ◽

Kentaro Nakajima ◽

Shinichiro Empuku ◽

Tomotaka Shibata ◽

...

Keyword(s):

Rectal Cancer ◽

Survival Rate ◽

Response Rate ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Pathological Response ◽

Complete Treatment ◽

Grade 3

720 Background: Fluorouracil-based chemoradiotherapy (CRT) is regarded as a standard perioperative treatment in locally advanced rectal cancer. We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug S-1. Methods: A multi-institutional (17 specialized centers), interventional phase II trial, was conducted from April 2009 to August 2011. For inclusion, patients must fulfill the following requirements before neoadjuvant CRT: (i) histologically proven rectal carcinoma; (ii) tumor located in the rectum (upper, lower); (iii) cancer classified as T3-4, N0–3 and M0; Two cycles of neoadjuvant CRT with S-1 (100 mg/m2 on days 1-5, 8-12, 22-26, and 29-33) was administered, and irradiation (total 45Gy/25fr, 1.8Gy/day, on days 1-5, 8-12, 15-19, 22-26, and 29-33) was performed. Total mesorectal excision was performed during the 4th and 8th week after the end of the neoadjuvant CRT. The primary endpoint is rate of complete treatment of neoadjuvant CRT. Secondary endpoints are response rate of neoadjuvant CRT, short-term clinical outcomes, rate of curative resection, and pathological response (grade2/3). Results: This trial included 37 patients (clinical StageIIA: 8, IIIB: 19, IIIC: 10; tumor located in the upper rectum; 4, the lower rectum; 33). A complete treatment of neoadjuvant CRT was found in 86.5% of patients (95%CI;75.5-97.5%), and an adverse event (grade 3/4) occurred in 4 patients(11.1%). Response rate (PR/CR;RECIST 1.0) was 56.8% (95%CI; 40.8-72.7%), and pathologic response rate (grade2/3) was 48.6% (95%CI; 32.5-64.8%). The median operating time was 448.5 min (IQR 340.5-505.5), and median blood loss was 422.5 mL (IQR 182.5-1125). Grade 3-4 postoperative complications occurred in 6 (16.7%) patients. The most common grade 3 or 4 postoperative complication was anastomotic leakage (2 [5.6%]). The 3-year overall survival rate was 88.5%. The 3-year disease free survival rate was 70.9%. Median length of follow-up was 42 months. Conclusions: A neoadjuvant-synchronus S-1+Radiotherapy for locally advanced rectal cancer is feasible in terms of pathological response, adverse events, accompany with favorable long-term outcome. Clinical trial information: 03396.

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