Long-term effect of peripheral sensory neuropathy (PSN) of 3 or 6 months oxaliplatin-based adjuvant chemotherapy for stage III colon cancer: ACHIEVE as part of the IDEA collaboration

BackgroundThe International Duration Evaluation of Adjuvant chemotherapy project investigated whether a shorter duration of oxaliplatin-based adjuvant chemotherapy was as effective as 6 months of identical chemotherapy for resected stage III colon cancer. As part of this project, we report safety data from the Japanese ACHIEVE study (JFMC47-1202-C3).Patients and methodsACHIEVE was an open-label, multicentre trial randomising patients with stage III colon cancer to receive 3 m or 6 m of mFOLFOX6/CAPOX after surgery. Choice of regimen was declared before randomisation by a site investigator.ResultsBetween August 2012 and June 2014, 1313 patients were enrolled and, of those, 1277 were analysed for the safety analysis, with 635 in arm 6 (mFOLFOX6, n=158; CAPOX, n=477) and 642 in arm 3 (mFOLFOX6, n=161; CAPOX, n=481). Grade 3 or worse peripheral sensory neuropathy (PSN) developed in 5%/0.6% of patients receiving mFOLFOX6 in arm 6/3 (p=0.019) and 6%/1% of those receiving CAPOX in arm 6/3 (p<0.001). Similarly, grade 2 or worse PSN developed in 36%/11% of patients receiving mFOLFOX6 in arm 6/3 (p<0.001) and 37%/14% of those receiving CAPOX in arm 6/3 (p<0.001). An association between baseline creatinine clearance (CCr) and adverse events (AEs) was found that patients with CAPOX were significantly more likely to develop AEs ≥grade 3 when they had a CCr ≤50 (OR 1.67; p=0.048).ConclusionsWe confirmed in the Japanese population that the shorter duration of adjuvant chemotherapy resulted in a significant reduction of PSN. In patients with CAPOX, renal function was significantly related to severe AEs.Trial registration numberUMIN000008543, Results.

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Safety analysis of FOLFOX as adjuvant chemotherapy for stage III colon cancer in phase II study (NORTH/HGCSG1003): Detailed analysis of peripheral sensory neuropathy.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.701 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 701-701

Author(s):

Susumu Sogabe ◽

Satoshi Yuki ◽

Hiraku Fukushima ◽

Norihiko Takahashi ◽

Toshiaki Shichinohe ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Phase Ii ◽

Phase Ii Study ◽

Sensory Neuropathy ◽

Japanese Patients ◽

Stage Iii ◽

Stage Iii Colon Cancer ◽

Grade 3 ◽

Resected Stage

701 Background: Oxaliplatin-containing regimen is a standard adjuvant chemotherapy for resected stage III colon cancer. Oxaliplatin-containing regimens were investigated for their efficacy in patients with resected stage III colon cancer in MOSAIC and XELOXA studies. Since these two international randomized studies were performed outside of Japan, we conducted a phase II study (NORTH/HGCSG1003) to assess the efficacy and safety of FOLFOX as adjuvant chemotherapy in Japanese patients (pts) with resected stage III colon cancer (UMIN ID: 000004590). Methods: This phase II study enrolled patients with resected stage III colon cancer. Patients received 12 biweekly cycles of FOLFOX4 or mFOLFOX6. Sample size was determined to be 243 pts. Primary endpoint was DFS. Secondary endpoints included overall survival (OS) and safety. Results: From September 2010 to March 2013, 273 pts were enrolled at 28 institutions. Safety analysis included 265 patients who received FOLFOX. Patients characteristics were as follows: median age, 65 (33-84); male/female: 131/134; PS 0/1:258/7; stage IIIA/IIIB/IIIC: 37/197/31; colon/rectosigmoid: 214/51. The most common grade 3-4 adverse events were neutrophil count decreased (48.1%), platelet count decreased (2.3%), and allergic reaction (1.5%). The incidence of peripheral sensory neuropathy (PSN) was 41.9% (grade 1), 38.1% (grade 2), and 6.4% (grade 3). PSN tended to be serious depending on the cumulative dose of oxaliplatin (table 1). Median cumulative dose of oxaliplatin at which PSN occurred were as follows: grade 1; 170 mg/m2, ≥ grade 2; 850 mg/m2, ≥ grade 3; (-). The median number of cycles of chemotherapy was 12, and the completion treatment rate was 80.4%. There was no treatment-related death. Conclusions: In Japanese patients with stage III colon cancer, FOLFOX is a well-tolerable regimen as adjuvant chemotherapy. Clinical trial information: 000004590. [Table: see text]

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Faculty Opinions recommendation of Adjuvant chemotherapy use and adverse events among older patients with stage III colon cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2627959.2302054 ◽

2010 ◽

Author(s):

Lodovico Balducci

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Adverse Events ◽

Older Patients ◽

Stage Iii ◽

Stage Iii Colon Cancer

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Faculty Opinions recommendation of Effect of adjuvant chemotherapy on survival of patients with stage III colon cancer diagnosed after age 75 years.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717952620.793458124 ◽

2012 ◽

Author(s):

Werner Scheithauer

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Stage Iii ◽

Stage Iii Colon Cancer

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Phase II study of an oxaliplatin-based regimen for relapsed colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy (INSPIRE study)

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-021-04232-2 ◽

2021 ◽

Author(s):

Keiichiro Ishibashi ◽

Toru Aoyama ◽

Masahito Kotaka ◽

Hironaga Satake ◽

Yasushi Tsuji ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Sensory Neuropathy ◽

Progression Free Survival ◽

First Line ◽

Secondary Endpoints ◽

Grade 3 ◽

Peripheral Sensory ◽

Line Chemotherapy

Abstract Background The aim of this study was to evaluate the efficacy and safety of first-line chemotherapy with re-introduction of oxaliplatin (OX) more than 6 months after adjuvant chemotherapy including OX. Methods Stage II/III colon cancer patients with neuropathies of grade ≤ 1 who relapsed more than 6 months after adjuvant chemotherapy including OX were considered eligible. Eligible patients were treated with 5-fluorouracil, l-leucovorin and OX plus molecularly targeted agents or capecitabine and OX plus bevacizumab (BV) or S-1 and OX plus BV. The primary endpoint was the progression-free survival (PFS), and the secondary endpoints were the overall survival (OS), response rate (RR) and toxicity. Results A total of 50 patients were enrolled between September 2013 and May 2019. Twelve patients received 5-fluorouracil, l-leucovorin and OX (FOLFOX) plus BV, 21 patients received capecitabine and OX plus BV, 10 patients received S-1 and OX plus BV and 7 patients received FOLFOX plus cetuximab or panitumumab. The median PFS was 11.5 months (95% confidence interval [CI] 8.3–16.0), the median OS was 45.4 months (95% CI 37.4–NA), and the RR was 56.0% (95% CI 42.3–68.8). Adverse events of grade ≥ 3 that occurred in ≥ 5% of cases were neutropenia in 6 patients (12%), peripheral sensory neuropathy in 5 patients (10%), diarrhea in 4 patients (8%), hypertension in 4 patients (8%), anorexia in 3 patients (6%) and allergic reactions in 3 patients (6%). Conclusions First-line chemotherapy with re-introduction of OX more than 6 months after adjuvant chemotherapy including OX can be used safely with expected efficacy for relapsed colon cancer patients.

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