Relationship Between Metformin Use and Recurrence and Survival in Patients With Resected Stage III Colon Cancer Receiving Adjuvant Chemotherapy: Results From North Central Cancer Treatment Group N0147 (Alliance)

PURPOSE To develop recommendations for duration of adjuvant chemotherapy with a fluoropyrimidine and oxaliplatin for patients with completely resected stage III colon cancer based on the results of trials of 3 months compared with 6 months of treatment. METHODS ASCO convened an Expert Panel and conducted a systematic review of relevant studies. The guideline recommendations were based on the review of evidence by the Expert Panel. RESULTS Pooled data from the six International Duration Evaluation of Adjuvant Chemotherapy (IDEA) Collaboration randomized controlled trials comprise the evidence base for these guideline recommendations. RECOMMENDATIONS The recommendations for therapy duration apply to patients with completely resected stage III colon cancer who are being offered adjuvant chemotherapy with oxaliplatin and a fluoropyrimidine. Recommendations are informed by the findings of a recent pooled analysis of clinical trials that compared 6 months versus 3 months of oxaliplatin-based chemotherapy. For patients at a high risk of recurrence (T4 and/or N2), adjuvant chemotherapy should be offered for a duration of 6 months. For patients at a low risk of recurrence (T1, T2, or T3 and N1), either 6 months of adjuvant chemotherapy or a shorter duration of 3 months may be offered on the basis of a potential reduction in adverse events and no significant difference in disease-free survival with the 3-month regimen. In determining duration of therapy, the Expert Panel recommends a shared decision-making approach, taking into account patient characteristics, values and preferences, and other factors and including a discussion of the potential for benefit and risks of harm associated with treatment duration. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

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The effect of comorbidity on the use of adjuvant chemotherapy and type of regimen for curatively resected stage III colon cancer patients

Cancer Medicine ◽

10.1002/cam4.632 ◽

2016 ◽

Vol 5 (5) ◽

pp. 871-880 ◽

Cited By ~ 14

Author(s):

Mei‐Chin Hsieh ◽

Trevor Thompson ◽

Xiao‐Cheng Wu ◽

Timothy Styles ◽

Mary B. O'Flarity ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Stage Iii ◽

Stage Iii Colon Cancer ◽

Resected Stage

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Fluorouracil Plus Leucovorin as Effective Adjuvant Chemotherapy in Curatively Resected Stage III Colon Cancer: Results of the Trial adjCCA-01

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.6.1787 ◽

2001 ◽

Vol 19 (6) ◽

pp. 1787-1794 ◽

Cited By ~ 82

Author(s):

Rainer Porschen ◽

Andreas Bermann ◽

Thomas Löffler ◽

Gregor Haack ◽

Klaus Rettig ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Adjuvant Treatment ◽

Disease Free Survival ◽

Stage Iii ◽

Postoperative Treatment ◽

Free Survival ◽

Stage Iii Colon Cancer ◽

Resected Stage ◽

Disease Free

PURPOSE: Adjuvant postoperative treatment with fluorouracil (5-FU) and levamisole in curatively resected stage III colon cancer significantly reduces the risk of cancer recurrence and improves survival. Biochemical modulation of 5-FU with leucovorin has resulted in increased remission rates in metastatic colorectal cancer, thus reflecting an increased tumor-cell kill. The impact of 5-FU plus leucovorin on survival and tumor recurrence was analyzed in comparison with the effects of 5-FU plus levamisole in the prospective multicentric trial adjCCA-01. PATIENTS AND METHODS: Patients with a curatively resected International Union Against Cancer stage III colon cancer were stratified according to T, N, and G category and randomly assigned to receive one of the two adjuvant treatment schemes: 5-FU 400 mg/m2 body-surface area intravenously in the first chemotherapy course, then 450 mg/m2 × 5 days; 12 cycles, plus leucovorin 100 mg/m2 (arm A), or 5-FU plus levamisole (Moertel scheme; arm B). RESULTS: Six hundred eighty (96.9%) of 702 patients enrolled onto this study were eligible. After a median follow-up time of 46.5 months, the 5-FU plus leucovorin combination significantly improved disease-free survival (P = .037) and significantly decreased overall mortality (P = .0089) in comparison with 5-FU plus levamisole. In a multivariate proportional hazards model, adjuvant chemotherapy emerged as a significant prognostic factor for survival (P = .0059) and disease-free survival (P = .03). Adjuvant treatment with 5-FU plus levamisole as well as with 5-FU plus leucovorin was generally well tolerated; only a minority of patients experienced grade 3 and 4 toxicities. CONCLUSION: After a curative resection of a stage III colon cancer, adjuvant treatment with 5-FU plus leucovorin is generally well tolerated and significantly more effective than 5-FU plus levamisole in reducing tumor relapse and improving survival.

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Adjuvant systemic chemotherapy for stages II and III colon cancer after complete resection: a clinical practice guideline

Current Oncology ◽

10.3747/co.23.3330 ◽

2016 ◽

Vol 23 (6) ◽

pp. 418 ◽

Cited By ~ 15

Author(s):

B.M. Meyers ◽

R. Cosby ◽

F. Quereshy ◽

D. Jonker

Keyword(s):

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Practice Guideline ◽

Stage Ii ◽

Stage Iii ◽

Cochrane Library ◽

Stage Iii Colon Cancer ◽

Resected Stage ◽

Stage Ii Colon Cancer

Background Updated practice guidelines on adjuvant chemotherapy for completely resected colon cancer are lacking. In 2008, Cancer Care Ontario’s Program in Evidence-Based Care developed a guideline on adjuvant therapy for stages ii and iii colon cancer. With newer regimens being assessed in this patient population and older agents being either abandoned because of non-effectiveness or replaced by agents that are more efficacious, a full update of the original guideline was undertaken.Methods Literature searches (January 1987 to August 2015) of medline, embase, and the Cochrane Library were conducted; in addition, abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress were reviewed (the latter for January 2007 to August 2015). A practice guideline was drafted that was then scrutinized by internal and external reviewers whose comments were incorporated into the final guideline.Results Twenty-six unique reports of eighteen randomized controlled trials and thirteen unique reports of twelve meta-analyses or pooled analyses were included in the evidence base. The 5 recommendations developed included 3 for stage ii colon cancer and 2 for stage iii colon cancer.Conclusions Patients with completely resected stage iii colon cancer should be offered adjuvant 5-fluorouracil (5fu)–based chemotherapy with or without oxaliplatin (based on definitive data for improvements in survival and disease-free survival). Patients with resected stage ii colon cancer without “high-risk” features should not receive adjuvant chemotherapy. For patients with “high-risk” features, 5fu-based chemotherapy with or without oxaliplatin should be offered, although no clinical trials have been conducted to conclusively demonstrate the same benefits seen in stage iii colon cancer.

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Severe rhabdomyolysis related to oxaliplatin adjuvant therapy for colorectal cancer

BMJ Case Reports ◽

10.1136/bcr-2018-228673 ◽

2019 ◽

Vol 12 (4) ◽

pp. e228673 ◽

Cited By ~ 2

Author(s):

Ana Pissarra ◽

Mariana Malheiro ◽

Leonor Vasconcelos Matos ◽

Ana Neto Plácido

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Stage Iii ◽

Standard Chemotherapy ◽

Postoperative Adjuvant Chemotherapy ◽

Stage Iii Colon Cancer ◽

Distal Muscle ◽

Common Cancer ◽

Resected Stage

Colorectal cancer is the third most common cancer in men and the second in women. The standard chemotherapy regiment in stage III colon cancer is based in oxaliplatin. The most common side effects include neutropenia, peripheral neuropathy, vomiting and diarrhoea. Rhabdomyolysis due to oxaliplatin is rare, and there are no established guidelines for managing this adverse event. This report describes a case of a 52-year-old man, with a resected stage III colon cancer that started postoperative adjuvant chemotherapy with capecitabine plus oxaliplatin. After the second cycle, the patient developed distal muscle pain and weakness, with a total inability to walk. Blood tests showed an elevated creatine kinase and renal injury. Severe drug-related rhabdomyolysis was diagnosed. The goal of this case report is to discuss the side effect of adjuvant chemotherapy, given its rarity and severity.

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Influence of KRAS mutations on outcome in patients with curatively resected stage III colon cancer treated with adjuvant chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14536 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e14536-e14536

Author(s):

Piercarlo Saletti ◽

Martina Nucifora ◽

Sara De Dosso ◽

Alessandra Spitale ◽

Nora Sahnane ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Single Agent ◽

Disease Free Survival ◽

Stage Iii ◽

Treatment Modalities ◽

Rank Test ◽

Kras Mutations ◽

Stage Iii Colon Cancer ◽

Resected Stage

e14536 Background: Adjuvant chemotherapy improves survival in patients with stage III colon cancer (CC) after curative resection, and oxaliplatin in combination with fluoropyrimidine-based regimens has been established as a standard treatment. KRAS mutations could predict oxaliplatin sensitivity in CC cells, as recently demonstrated. Here, we profiled KRAS and correlated it with outcome in stage III CC patients who underwent adjuvant chemotherapy. Methods: Eligible patients were those with resected stage III CC who underwent 6-months adjuvant chemotherapy, either with single-agent fluoropyrimidine (FP: modulated 5FU or capecitabine) or with oxaliplatin-based regimens (O-FP: FOLFOX or XELOX). DNA extraction was performed on formalin-fixed paraffin-embedded sections, and KRAS mutations were analyzed by direct sequencing. Disease-free survival (DFS) and overall survival (OS) analyses were computed using the Kaplan-Meier method and the Log-rank test. Results: The study population included 261 patients: 115 treated with FP, 146 O-FP. We identified KRAS mutations in 71/261 (27.4%) cases, of which 33 (46.5%) received FP, and 38 (53.5%) O-FP. In wild-type (wt) KRAS cases, DFS and OS group did not significantly differ between the two treatment modalities [in months, FP vs O-FP - median OS: 62.0 vs 49.6, HR: 1.12 (95% CI: 0.65; 1.92); median DFS: 57.1 vs 44.4, HR: 0.93 (95% CI: 0.55; 1.56)]. In patients treated with FP, a worse DFS [in months, mutant vs wt - median DFS: 46.0 vs 57.1, p=0.04; HR: 1.86 (95% CI: 1.01; 3.41)] and a trend toward a worse OS in months, mutant vs wt - median OS: 56.1 vs 62.0, p=0.08; HR: 1.71 (95% CI: 0.94; 3.10)] were observed in KRAS mutated patients. On the contrary, DFS and OS were not statistically different for mutated and wt KRAS patients treated with O-FP [in months, mutant vs wt - median DFS: 43.7 vs 44.4, p=0.62; HR: 1.17 (95% CI: 0.63; 2.18); median OS: 48.9 vs 49.6, p=0.77; HR: 1.11 (95% CI: 0.55; 2.23). Conclusions: Our results suggest that curatively resected stage III CC patients exhibiting wt KRAS status might benefit from FP alone. On the contrary, an oxaliplatin-containing regimen should be recommended in KRAS mutated patients.

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A Japanese multicenter phase II study of adjuvant chemotherapy with mFOLFOX6/CAPOX for stage III colon cancer treatment after D2/D3 lymphadenectomy

Surgery Today ◽

10.1007/s00595-019-1771-y ◽

2019 ◽

Vol 49 (6) ◽

pp. 498-506 ◽

Cited By ~ 2

Author(s):

Kazuhiko Yoshimatsu ◽

Keiichiro Ishibashi ◽

Keiji Koda ◽

Hajime Yokomizo ◽

Noritaka Oda ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Treatment ◽

Phase Ii ◽

Phase Ii Study ◽

Stage Iii ◽

D3 Lymphadenectomy ◽

Stage Iii Colon Cancer ◽

Multicenter Phase

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Relationship between metformin use and recurrence and survival in patients (pts) with resected stage III colon cancer (CC) receiving adjuvant chemotherapy: Results from NCCTG N0147 (Alliance).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.3531 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. 3531-3531 ◽

Cited By ~ 1

Author(s):

Preet Paul Singh ◽

Qian Shi ◽

Nathan R. Foster ◽

Axel Grothey ◽

Suresh Nair ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Stage Iii ◽

Stage Iii Colon Cancer ◽

Resected Stage

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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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North Japan multicenter phase II study of oxaliplatin-containing regimen as adjuvant chemotherapy for stage III colon cancer (NORTH/HGCSG1003).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.807 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 807-807

Author(s):

Toshiaki Shichinohe ◽

Satoshi Yuki ◽

Norihiko Takahashi ◽

Hiroshi Nakatsumi ◽

Yasuyuki Kawamoto ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Phase Ii ◽

Primary Endpoint ◽

Phase Ii Study ◽

Disease Free Survival ◽

Japanese Patients ◽

Stage Iii ◽

Stage Iii Colon Cancer ◽

Resected Stage

807 Background: FOLFOX and XELOX are standard adjuvant chemotherapy for resected stage III colon cancer. MOSAIC and XELOXA trials were performed outside of Japan, thus, we conducted a phase II study (NORTH/HGCSG1003) to assess the efficacy and safety of FOLFOX as adjuvant chemotherapy for 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 cycles of FOLFOX4 or mFOLFOX6. Sample size was determined to be 243 pts. Primary endpoint was disease-free survival (DFS). We assumed an expected 3-year DFS rate of 81.2% in this study. Secondary endpoints included overall survival (OS) and safety. In this meeting, we present for the 3-year DFS rate. Results: From Sep 2010 to Mar 2013, 273 pts were enrolled at 28 institutions. Full 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%), peripheral sensory neuropathy (6.4%), platelet count decreased (2.3%), and allergic reaction (1.5%). The median number of cycles of FOLFOX was 12, and the completion treatment rate was 80.4%. There was no treatment-related death. The 3-year DFS rate was 75.2 percent (95% confidence interval, 69.6 to 80.0). Conclusions: In Japanese patients with stage III colon cancer, FOLFOX is a well-tolerable regimen as adjuvant chemotherapy. In this trial, the 3-year DFS rate of primary endpoint was not meet the expectation (81.2%). However, the 3-year DFS rate in this trial was similar to several pivotal trials. We plan to do subset analysis. Clinical trial information: UMIN000004590.

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