Clinical effectiveness of adjuvant chemotherapy (AC) with or without oxaliplatin following neoadjuvant chemoradiotherapy (nCRT) in stage II rectal cancer (RC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 686-686
Author(s):  
Jonathan M. Loree ◽  
Hagen F. Kennecke ◽  
Erin Diana Powell ◽  
Rachel Anne Goodwin ◽  
Patricia A. Tang ◽  
...  
Keyword(s):  
High Risk ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Clinical Effectiveness ◽  
Margin Status ◽  
Stage Ii ◽  
Curative Surgery ◽  
Small Magnitude ◽  
Cox Models ◽  
Lymph Node Sampling

686 Background: Use of AC in RC following nCRT is controversial because of concerns regarding its potentially small magnitude of benefit. We aimed to 1) examine real-world patterns of AC use in stage II RC and assess its impact on outcomes and 2) determine whether the addition of oxaliplatin to fluoropyrimidines modifies effectiveness. Methods: Using a cohort of yp stage II RC patients from 5 Canadian centers that underwent curative surgery, we assessed the relationship between AC +/- oxaliplatin and overall (OS) and disease free survival (DFS). Cox models adjusting for age, gender, ECOG, and high risk features (T4 lesion, poor differentiation, inadequate lymph node sampling, lymphovascular/perineural invasion, and obstruction/perforation) were constructed. Results: Among 485 pts, 74% received AC of whom 19% received oxaliplatin-based treatment. Median follow up was 4.5 yrs. Pts in the AC group were younger (median age 61 vs 64; P= 0.003) and had higher rates of TME (82% vs 79%; P= 0.049), but they had similar demographics, ECOG, high risk features, preoperative CEA, margin status and nCRT regimen when compared to pts in the non-AC group (all P> 0.05). Multivariate analyses demonstrated that receipt of any AC (OS HR 0.93 95% CI 0.58-1.50 P =0.77; DFS HR 0.91 95% CI 0.58-1.43 P =0.69), fluoropyrimidine AC (OS HR 0.82 95% CI 0.49-1.36 P =0.44; DFS HR 0.83 95% CI 0.51-1.34 P =0.44), or oxaliplatin-based AC (OS HR 1.37 95% CI 0.74-2.55 P =0.32; DFS HR 1.17 95% CI 0.66-2.05 P =0.59) did not improve outcomes versus no AC. In subgroup analyses that stratified pts by high risk features, presence of 1, 2, or 3 high risk factors, preoperative CEA and margin status, AC did not result in better OS or DFS in any subgroup. A further exploratory analysis that focused only on those receiving AC within 12 weeks of surgery did not reveal any consistent correlations between AC and survival. Conclusions: Use of fluoropyrimidine or oxaliplatin-based AC in this multi-institutional cohort of yp stage II RC pts after nCRT did not improve outcomes compared to observation. Conventional high risk features used to risk stratify stage II colon cancer for AC decision making have limited utility in RC after nCRT.

Evaluation of the prognostic value of guanylyl cyclase C (GCC) lymph node (LN) classification in patients with stage II colon cancer: A pooled analysis.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 443-443
Author(s):  
Daniel J. Sargent ◽  
Qian Shi ◽  
Murray B. Resnick ◽  
Stephen Lyle ◽  
Michael O. Meyers ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Clinical Outcomes ◽  
Prognostic Value ◽  
Disease Free Survival ◽  
Strong Relationship ◽  
Low Risk ◽  
Stage Ii ◽  
Risk Status ◽  
Cox Models

443 Background: Identification of a sensitive and specific prognostic marker would aid in the management of patients (pts) with standard histopathology node negative colon cancer (CC). We conducted a pooled individual pt data analysis to confirm the prognostic value of GCC for disease recurrence in untreated stage II CC. Methods: GCC mRNA was quantified by RT-qPCR using formalin-fixed LN from 310 stage II pts diagnosed from 1991-2006 enrolled in two studies (Sargent 2011 [study1] and Haince 2009 [study2]). Patients were classified by GCC LN ratio (LNR) (high risk: LNR ≥ 0.1; low risk: LNR < 0.1), with LNR defined as number of GCC positive LN divided by number of informative LNs. Clinical outcomes included time to recurrence (TTR), overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Stratified log-rank tests and multivariate Cox models assessed the association between clinical outcomes and GCC LN status. Results: The 5-year recurrence rate in study 1 (n=241) was 15.8%, 24.9% in study 2 (n=69). GCC LNR high risk pts had significantly higher risk of TTR, OS, DSS and DFS, which remained after adjusting for age, T stage, grade, number of LNs examined, and presence of lymphovascular invasion ( Table ). In a secondary analysis of low risk stage II pts (T3, ≥12 LNs examined, and negative surgical margins, n=241), a strong relationship between GCC LNR and each endpoint remained (TTR HR=4.34, 95% CI=2.07 – 9.13, p<0.001). Conclusions: Pts with GCC LNR high risk status have significantly poorer outcomes compared to pts with low risk status, particularly among those traditionally considered to be low risk. [Table: see text]

scholarly journals Adjuvant Gemcitabine-Oxaliplatin (GeMOX) after Curative Surgery in High-risk Patients with Cholangiocarcinoma

2009 ◽  
Vol 3 ◽  
pp. CMO.S3360
Author(s):  
Bernard Paule ◽  
Paola Andreani ◽  
Marie-Pierre Bralet ◽  
Catherine Guettier ◽  
René Adam ◽  
...  
Keyword(s):  
Survival Rate ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Curative Surgery ◽  
Free Survival ◽  
High Risk Factors ◽  
Risk Patients ◽  
Disease Free Survival Rate ◽  
Disease Free

Background There is no standard adjuvant chemotherapy to prevent recurrent cholangiocarcinoma (CCA), a rare cancer with poor prognosis. We assessed the efficacy and safety of GEMOX on intrahepatic and hilar CCA with high-risk factors after curative surgery. Patients and Methods Twenty two patients (mean age: 57 years old) with CCA received 6 cycles of GEMOX: gemcitabine 1,000 mg/m2 on day 1 and oxaliplatin 85 mg/m2 on day 2, q3w after a curative surgery. Results All patients completed 6 cycles of GEMOX. EGFR membranous expression was present in 20 CCA. The 5-year survival rate was 56% (CI 95%: 25.7–85.4); 2-year disease free survival rate was 28% (CI 95%: 3.4–52.6). Median time to progression was 15 months. The rate of recurrence after surgery and chemotherapy was 63% (14/22). Two patients died of disease progression. Twelve patients received cetuximab/GEMOX at the time of relapse. Six died after 12 months (9–48 months), three are still alive suggesting a clinical applicability of EGFR inhibitors in CCA. Conclusion Adjuvant chemotherapy with GEMOX alone seems ineffective in intrahepatic and hilar CCA with a high risk of relapse. Additional studies including targeted therapies to circumvent such poor chemosensitivity are needed.

scholarly journals Use of a Combination of CEA and Tumor Budding to Identify High-risk Patients with Stage II Colon Cancer

2017 ◽  
Vol 32 (3) ◽  
pp. 267-273 ◽  
Author(s):  
Changzheng Du ◽  
Weicheng Xue ◽  
Fangyuan Dou ◽  
Yifan Peng ◽  
Yunfeng Yao ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Disease Progression ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Tumor Budding ◽  
High Risk Patients ◽  
Prognostic Accuracy ◽  
Risk Patients ◽  
Stage Ii Colon Cancer

Background High-risk patients with stage II colon cancer may benefit from adjuvant chemotherapy, but identifying this patient population can be difficult. We assessed the prognosis value for predicting tumor progression in patients with stage II colon cancer, of a panel of 2 biomarkers for colon cancer: tumor budding and preoperative carcinoembryonic antigen (CEA). Methods Consecutive patients (N = 134) with stage II colon cancer who underwent curative surgery from 2000 to 2007 were included. Multivariate analysis was used to evaluate the association of CEA and tumor budding grade with 5-year disease-free survival (DFS). The prognostic accuracy of CEA, tumor budding grade and the combination of both (CEA-budding panel) was determined. Results The study found that both CEA and tumor budding grade were associated with 5-year DFS. The prognostic accuracy for disease progression was higher for the CEA-budding panel (82.1%) than either CEA (70.9%) or tumor budding grade (72.4%) alone. Conclusions The findings indicate that the combination of CEA levels and tumor budding grade has greater prognostic value for identifying patients with stage II colon cancer who are at high-risk for disease progression, than either marker alone.

Identification of risk factors for stage II colon cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 375-375
Author(s):  
Sho Sawazaki ◽  
Manabu Shiozawa ◽  
Koji Numata ◽  
Masakatsu Numata ◽  
Teni Godai ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Disease Free Survival ◽  
Lymphatic Invasion ◽  
Clinicopathological Features ◽  
Stage Ii ◽  
Tumor Diameter ◽  
Free Survival ◽  
Stage Ii Colon Cancer ◽  
Disease Free

375 Background: The use of adjuvant chemotherapy remains controversial in Stage II colon cancer. However, patients with specific clinicopathological features are thought to have high risk for recurrence. The aim of this study was to identify the subgroup of patients at great risk, by investigating the clinicopathological features associated with poor survived in Stage II. Methods: A total of 282 patients with Stage II colon cancer who underwent curative resection from January 1990 to September 2007 at Kanagawa Cancer Center were enrolled. Then, the clinicopathological data of the patients were retrospectively evaluated. Disease-free survival rates were calculated by the Kaplan-Meier method, and survival curves were compared by the log-rank test. Cox’s regression analysis was used for multivariate analyses. P values <0.05 were considered to be statistically significant. Results: The median follow up was 62.5 months. The 5-year disease-free survival was 92.2% in the study group as a whole. Among the recurrent patients (n=23), the most recurrent site was the liver (n=11, 44%), followed by lung (n=6, 24%), and peritoneum (n=5, 20%). Univariate analysis for 5-year disease-free survival identified two factors; tumor diameter (>5cm vs…5cm, p=0.018), and lymphatic invasion (p=0.009). Multivariate analysis for 5-year disease-free survival identified two independent factors; tumor diameter (hazard ratio [HR], 4.82; 95% CI, 1.55-15.0; p=0.006), and lymphatic invasion (HR, 4.15; 95% CI, 1.68-10.2; p=0.002). The 5-year disease-free survival differed significantly among patients with neither of these prognostic factors (98.6%), those with only 1 factor (93.3%), and those with 2 factors (76.6%, p=0.000). Conclusions: Patients with stage II colon cancer who have both 5cm in diameter and lymphatic invasion are at high risk for recurrence. The use of adjuvant chemotherapy should be considered in this subgroup of patients.

CD3+ tumor-infiltrating lymphocytes (TILs) as prognostic in patients (pts) with stage II colon cancer (CC) not treated with adjuvant chemotherapy (ADJ).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 167-167
Author(s):  
Edoardo Francini ◽  
Fang-Shu Ou ◽  
Stefano Lazzi ◽  
Roberto Petrioli ◽  
Andrea Giovanni Multari ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Multivariable Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Clinical Decision ◽  
Stage Ii ◽  
Prognostic Impact ◽  
Curative Surgery ◽  
Cox Models ◽  
Risk Of Death ◽  
The Impact

167 Background: Previous studies have reported high TILs are a favorable prognostic factor in stage II CC. However, whether the impact of TILs on overall survival (OS) differs among pts who did or did not receive ADJ is still to be determined. We assessed the prognostic value of CD3+ TILs in pts with stage II CC according to whether they received ADJ or not (no-ADJ). Methods: Pts treated with curative surgery for stage II CC (2002-2013) were identified through the Santa Maria alle Scotte Hospital database. CD3+ TILs at the invasive front, center of tumor, and stroma, were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as > 20%. Pts were classified as high or low TILs (L-TILs) and ADJ or no-ADJ. Cox models were used to assess OS with hazard ratio estimates (95% CI). Results: Of the 678 pts included (356 deaths), 137 (20%) received ADJ while 541 (80%) did not. ADJ comprised fluoropyrimidine +/- oxaliplatin. Median follow-up was 8.5 years. The distributions of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ pts had a significantly longer OS (P < .0001) regardless of the TILS rate while L-TILs/no ADJ had significantly shorter OS and higher risk of death (HR = 1.41; 95% CI, 1.06-1.88; P < .0001) [See table]. On multivariable analysis, adjusting for perforation, obstruction, T-stage, grade, < 12 lymph nodes resected, lymphovascular and perineural invasion, the adverse prognostic impact of L-TILs (vs H-TILs) in no-ADJ pts was confirmed (HR = 1.36; 95% CI 1.02, 1.82; P = .0373). Conclusions: Low CD3+ TILs rate was independently associated with shorter OS in stage II CC pts who did not receive ADJ, but was not prognostic among pts who had ADJ. These data suggest a potentially different impact of TILs in chemo-treated vs -untreated stage II CC which could affect clinical decision making. [Table: see text]

scholarly journals Addition of Platinum Derivatives to Fluoropyrimidine-Based Neoadjuvant Chemoradiotherapy for Stage II/III Rectal Cancer: Systematic Review and Meta-Analysis

2019 ◽  
Vol 111 (9) ◽  
pp. 887-902 ◽  
Author(s):  
Felix J Hüttner ◽  
Pascal Probst ◽  
Eva Kalkum ◽  
Matthes Hackbusch ◽  
Katrin Jensen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Pathological Complete Response ◽  
Meta Analysis ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Complete Response ◽  
Distant Recurrence ◽  
Stage Ii ◽  
Free Survival ◽  
Disease Free

Abstract Background Current guidelines recommend neoadjuvant therapy for patients with stage II or III rectal cancer. The addition of platinum derivatives to fluoropyrimidine-based chemoradiotherapy has been frequently investigated, but their role in this setting remains controversial. Methods PubMed, Cochrane Library, and Web of Science were systematically searched for randomized trials comparing chemoradiotherapy with or without platinum agents in stage II or III rectal cancer. Main outcome parameters were overall and disease-free survival, additional outcomes included pathological complete response, isolated local recurrence, distant recurrence, toxicity, and perioperative morbidity. Time-to-event data were pooled as hazard ratios (HRs) by the inverse variance method and binary outcomes as odds ratios (ORs) by the Peto method with their respective 95% confidence interval (CI). All statistical tests were two-sided. Results Ten randomized controlled trials with data on 5599 patients were included in the meta-analysis. Platinum derivatives did not statistically significantly improve overall survival (HR = 0.93, 95% CI = 0.82 to 1.05, P = .23), disease-free survival (HR = 0.91, 95% CI = 0.83 to 1.01, P = .07), or local recurrence (OR = 0.83, 95% CI = 0.66 to 1.05, P = .12). However, it led to a statistically significant increase of pathological complete response (OR = 1.31, 95% CI = 1.10 to 1.55, P = .002) and a statistically significant reduction of distant recurrence (OR = 0.78, 95% CI = 0.66 to 0.92, P = .004). Benefits were accompanied by higher rates of grade 3 or 4 toxicities. Conclusions Intensified neoadjuvant chemoradiotherapy with the addition of platinum derivatives cannot be recommended routinely because it did not improve overall or disease-free survival and was associated with increased toxicity. It needs to be elucidated whether the benefits in distant recurrence and pathological complete response may be advantageous for selected high-risk patients.

Impact of older age on the efficacy of newer adjuvant therapies in >12,500 patients (pts) with stage II/III colon cancer: Findings from the ACCENT Database

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4010-4010 ◽  
Author(s):  
N. A. Jackson McCleary ◽  
J. Meyerhardt ◽  
E. Green ◽  
G. Yothers ◽  
A. de Gramont ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Recurrence ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Phase Iii ◽  
Cox Models ◽  
Time To Death ◽  
Time To Recurrence ◽  
Clinically Meaningful Outcomes ◽  
The Impact

4010 Background: Prior studies suggested that older and younger pts with colon cancer receive similar benefit from IV fluoropyrimidine (FU) adjuvant (adj) therapy (rx). Combination and/or oral FU rx are increasingly given as adj rx. We sought to determine the impact of pts age <70 v ≥70 yrs on colon cancer recurrence and mortality from adj rx with these newer options. Methods: We used data from 10,499 pts <70 yrs and 2,170 pts ≥70 yrs in 6 phase III adj rx trials comparing IV FU to combinations with irinotecan, oxaliplatin or oral FU (capecitabine and UFT/LV) in stage II/III colon cancer from the ACCENT database. Endpoints were overall survival (OS; time to death), disease-free survival (DFS; time to recurrence or death), and time to recurrence (TTR; censoring at last follow-up). Cox models were stratified by age and adjusted for gender and stage; interaction testing was used to explore the differential benefit by age. Results: Approximately 75% of pts had stage III disease (74% age<70, 77% age≥70). OS, DFS, and TTR were statistically significantly improved for those in the experimental v control arms among pts <70 but not those >70 ( table ); the interaction between age and rx was statistically significant for all endpoints (p=0.01 for OS, DFS, and TTR). These results were consistent whether experimental rx was oxaliplatin-based, irinotecan-based or oral FU. Deaths in first 6 month of adj rx were not statistically significantly different between experimental and control arm. Conclusions: Our results show conclusively that pts >70 do not receive the same benefit from combination and/or oral FU as those <70. Any benefit, if present, compared to IV FU/LV would not be clinically meaningful. Outcomes of experimental (combination or oral FU) vs control (IV 5-FU) by treatment and age [Table: see text] [Table: see text]

Adjuvant Therapy in Rectal Cancer: Analysis of Stage, Sex, and Local Control—Final Report of Intergroup 0114

2002 ◽  
Vol 20 (7) ◽  
pp. 1744-1750 ◽  
Author(s):  
J.E. Tepper ◽  
M. O’Connell ◽  
D. Niedzwiecki ◽  
D.R. Hollis ◽  
A.B. Benson ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Chemoradiation Therapy ◽  
Low Risk ◽  
Final Report ◽  
Recurrence Rates ◽  
Curative Surgery

PURPOSE: The gastrointestinal Intergroup studied postoperative adjuvant chemotherapy and radiation therapy in patients with T3/4 and N+ rectal cancer after potentially curative surgery to try to improve chemotherapy and to determine the risk of systemic and local failure. PATIENTS AND METHODS: All patients had a potentially curative surgical resection and were treated with two cycles of chemotherapy followed by chemoradiation therapy and two additional cycles of chemotherapy. Chemotherapy regimens were bolus fluorouracil (5-FU), 5-FU and leucovorin, 5-FU and levamisole, and 5-FU, leucovorin, and levamisole. Pelvic irradiation was given to a dose of 45 Gy to the whole pelvis and a boost to 50.4 to 54 Gy. RESULTS: One thousand six hundred ninety-five patients were entered and fully assessable, with a median follow-up of 7.4 years. There was no difference in overall survival (OS) or disease-free survival (DFS) by drug regimen. DFS and OS decreased between years 5 and 7 (from 54% to 50% and 64% to 56%, respectively), although recurrence-free rates had only a small decrease. The local recurrence rate was 14% (9% in low-risk [T1 to N2+] and 18% in high-risk patients [T3N+, T4N]). Overall, 7-year survival rates were 70% and 45% for the low-risk and high-risk groups, respectively. Males had a poorer overall survival rate than females. CONCLUSION: There is no advantage to leucovorin- or levamisole-containing regimens over bolus 5-FU alone in the adjuvant treatment of rectal cancer when combined with irradiation. Local and distant recurrence rates are still high, especially in T3N+ and T4 patients, even with full adjuvant chemoradiation therapy.

scholarly journals Neoadjuvant Chemotherapy in High-Risk Soft Tissue Sarcomas: Final Results of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups

2020 ◽  
Vol 38 (19) ◽  
pp. 2178-2186 ◽  
Author(s):  
Alessandro Gronchi ◽  
Emanuela Palmerini ◽  
Vittorio Quagliuolo ◽  
Javier Martin Broto ◽  
Antonio Lopez Pousa ◽  
...  
Keyword(s):  
High Risk ◽  
Soft Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Soft Tissue Sarcomas ◽  
Disease Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Nerve Sheath Tumor ◽  
Open Label ◽  
Cox Models

PURPOSE To determine whether the administration of histology-tailored neoadjuvant chemotherapy (HT) was superior to the administration of standard anthracycline plus ifosfamide neoadjuvant chemotherapy (A+I) in high-risk soft tissue sarcoma (STS) of an extremity or the trunk wall. PATIENTS AND METHODS This was a randomized, open-label, phase III trial. Patients had localized high-risk STS (grade 3; size, ≥ 5 cm) of an extremity or trunk wall, belonging to one of the following five histologic subtypes: high-grade myxoid liposarcoma (HG-MLPS); leiomyosarcoma (LMS), synovial sarcoma (SS), malignant peripheral nerve sheath tumor (MPNST), and undifferentiated pleomorphic sarcoma (UPS). Patients were randomly assigned in a 1:1 ratio to receive three cycles of A+I or HT. The HT regimens were as follows: trabectedin in HG-MLPS; gemcitabine plus dacarbazine in LMS; high-dose prolonged-infusion ifosfamide in SS; etoposide plus ifosfamide in MPNST; and gemcitabine plus docetaxel in UPS. Primary and secondary end points were disease-free survival (DFS) and overall survival (OS), estimated using the Kaplan-Meier method and compared using Cox models adjusted for treatment and stratification factors. The study is registered at ClinicalTrials.gov (identifier NCT01710176 ). RESULTS Between May 2011 and May 2016, 287 patients (UPS: n = 97 [33.8%]; HG-MLPS: n = 65 [22.6%]; SS: n = 70 [24.4%]; MPNST: n = 27 [9.4%]; and LMS: n = 28 [9.8%]) were randomly assigned to either A+I or HT. At the final analysis, with a median follow-up of 52 months, the projected DFS and OS probabilities were 0.55 and 0.47 (log-rank P = .323) and 0.76 and 0.66 (log-rank P = .018) at 60 months in the A+I arm and HT arm, respectively. No treatment-related deaths were observed. CONCLUSION In a population of patients with localized high-risk STS, HT was not associated with a better DFS or OS, suggesting that A+I should remain the regimen to choose whenever neoadjuvant chemotherapy is used in patients with high-risk STS.

scholarly journals Duration of Adjuvant Doublet Chemotherapy (3 or 6 months) in Patients With High-Risk Stage II Colorectal Cancer

2021 ◽  
Vol 39 (6) ◽  
pp. 631-641
Author(s):  
Timothy J. Iveson ◽  
Alberto F. Sobrero ◽  
Takayuki Yoshino ◽  
Ioannis Souglakos ◽  
Fang-Shu Ou ◽  
...  
Keyword(s):  
High Risk ◽  
Healthcare Providers ◽  
Disease Free Survival ◽  
Patient Choice ◽  
Stage Ii ◽  
Relative Contribution ◽  
Rectal Cancers ◽  
Stage Ii Colon Cancer ◽  
Reduced Toxicity ◽  
Duration Effect

PURPOSE: As oxaliplatin results in cumulative neurotoxicity, reducing treatment duration without loss of efficacy would benefit patients and healthcare providers. PATIENTS AND METHODS: Four of the six studies in the International Duration of Adjuvant Chemotherapy (IDEA) collaboration included patients with high-risk stage II colon and rectal cancers. Patients were treated (clinician and/or patient choice) with either fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) and randomly assigned to receive 3- or 6-month treatment. The primary end point is disease-free survival (DFS), and noninferiority of 3-month treatment was defined as a hazard ratio (HR) of < 1.2- v 6-month arm. To detect this with 80% power at a one-sided type one error rate of 0.10, a total of 542 DFS events were required. RESULTS: 3,273 eligible patients were randomly assigned to either 3- or 6-month treatment with 62% receiving CAPOX and 38% FOLFOX. There were 553 DFS events. Five-year DFS was 80.7% and 83.9% for 3-month and 6-month treatment, respectively (HR, 1.17; 80% CI, 1.05 to 1.31; P [for noninferiority] .39). This crossed the noninferiority limit of 1.2. As in the IDEA stage III analysis, the duration effect appeared dependent on the chemotherapy regimen although a test of interaction was negative. HR for CAPOX was 1.02 (80% CI, 0.88 to 1.17), and HR for FOLFOX was 1.41 (80% CI, 1.18 to 1.68). CONCLUSION: Although noninferiority has not been demonstrated in the overall population, the convenience, reduced toxicity, and cost of 3-month adjuvant CAPOX suggest it as a potential option for high-risk stage II colon cancer if oxaliplatin-based chemotherapy is suitable. The relative contribution of the factors used to define high-risk stage II disease needs better understanding.

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