Hepatectomy Followed by mFOLFOX6 Versus Hepatectomy Alone for Liver-Only Metastatic Colorectal Cancer (JCOG0603): A Phase II or III Randomized Controlled Trial

2021 ◽  
pp. JCO.21.01032
Author(s):  
Yukihide Kanemitsu ◽  
Yasuhiro Shimizu ◽  
Junki Mizusawa ◽  
Yoshitaka Inaba ◽  
Tetsuya Hamaguchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Randomized Controlled Trial ◽  
Adjuvant Chemotherapy ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Controlled Trial ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Randomized Controlled

PURPOSE Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC. PATIENTS AND METHODS In this phase II or III trial (JCOG0603), patients age 20-75 years with confirmed CRC and an unlimited number of liver metastatic lesions were randomly assigned to hepatectomy alone or 12 courses of adjuvant mFOLFOX6 after hepatectomy. The primary end point of phase III was disease-free survival (DFS) in intention-to-treat analysis. RESULTS Between March 2007 and January 2019, 300 patients were randomly assigned to hepatectomy alone (149 patients) or hepatectomy followed by chemotherapy (151 patients). At the third interim analysis of phase III with median follow-up of 53.6 months, the trial was terminated early according to the protocol because DFS was significantly longer in patients treated with hepatectomy followed by chemotherapy. With median follow-up of 59.2 months, the updated 5-year DFS was 38.7% (95% CI, 30.4 to 46.8) for hepatectomy alone compared with 49.8% (95% CI, 41.0 to 58.0) for chemotherapy (hazard ratio, 0.67; 95% CI, 0.50 to 0.92; one-sided P = .006). However, the updated 5-year overall survival (OS) was 83.1% (95% CI, 74.9 to 88.9) with hepatectomy alone and 71.2% (95% CI, 61.7 to 78.8) with hepatectomy followed by chemotherapy. In the chemotherapy arm, the most common grade 3 or higher severe adverse event was neutropenia (50% of patients), followed by sensory neuropathy (10%) and allergic reaction (4%). One patient died of unknown cause after three courses of mFOLFOX6 administration. CONCLUSION DFS did not correlate with OS for liver-only metastatic CRC. Adjuvant chemotherapy with mFOLFOX6 improves DFS among patients treated with hepatectomy for CRC liver metastasis. It remains unclear whether chemotherapy improves OS.

scholarly journals Post-hoc biomarker analyses of T4a/T4b gastric cancer from patients recruited into SAMIT, a phase III randomized controlled trial

2021 ◽  
Author(s):  
Takashi Oshima ◽  
Akira Tsuburaya ◽  
Kazuhiro Yoshida ◽  
Takaki Yoshikawa ◽  
Yohei Miyagi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Randomized Controlled Trial ◽  
Adjuvant Chemotherapy ◽  
Controlled Trial ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Phase Iii ◽  
P Value ◽  
Positive Effects ◽  
Randomized Controlled

Abstract Biomarkers for selecting gastric cancer (GC) patients likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy were searched for using samples of patients recruited into SAMIT, a phase III randomized controlled trial. Total RNA was extracted from 556 GC patients and the expression of 105 genes were quantified using real-time PCR. Genes predicting positive effects of sequential paclitaxel on overall survival (OS), disease-free survival (DFS), or cumulative incidence of relapse were identified based on p-values associated with the interaction between the biomarker and sequential paclitaxel or monotherapy group. Low VSNL1 and CD44v expression predicted the positive effects of sequential paclitaxel in all above three endpoints. In the patient subgroup with combined low expression of both genes, sequential paclitaxel therapy was associated with a significantly improved OS (hazard ratio [HR] = 0.48 [95% confidence interval (CI), 0.30–0.78]; p < 0.01; interaction p-value < 0.01), particularly in patients with stage IIIB GC (HR = 0.39 [95% CI, 0.20–0.75]; p < 0.01; interaction p-value < 0.01). In this study, two biomarkers were identified. Our findings might open up the way for clinical trials on biomarker-oriented postoperative adjuvant chemotherapy for locally advanced cancer.

A phase III study of the impact of a physical activity program on disease-free survival in patients with high-risk stage II or stage III colon cancer: A randomized controlled trial (NCIC CTG CO.21).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS3647-TPS3647
Author(s):  
Christopher M. Booth ◽  
Kerry S. Courneya ◽  
Janette L. Vardy ◽  
Derek J. Jonker ◽  
Sharlene Gill ◽  
...  
Keyword(s):  
Physical Activity ◽  
Colon Cancer ◽  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Face To Face ◽  
Randomized Controlled ◽  
Disease Free

TPS3647 Background: Observational data indicate that physical activity (PA) is strongly associated with colon-cancer specific survival. NCIC CTG CO.21 (CHALLENGE) is designed to determine the effects of a structured PA intervention on disease-control outcomes for survivors of high-risk stage II or III colon cancer who have completed adjuvant chemotherapy within the previous 2-6 months. Methods: Phase III randomized controlled trial. Target sample size of 962 patients is powered to detect a Hazard Ratio of 0.75 for disease-free survival (DFS). Trial participants will be stratified by centre, disease stage, body mass index, and performance status, and will be randomly assigned to a structured, individualized PA intervention or to general health education materials. The PA intervention will consist of a behavioural support program and supervised PA sessions delivered over a 3-year period, beginning with regular face-to-face sessions and tapering to less frequent face-to-face or telephone sessions. The goal of the PA program is to increase weekly PA by 10 MET hours/week. The PA program is delivered by physical activity consultants trained in exercise physiology and behavior change. Outcomes: The primary endpoint is DFS. Important secondary endpoints include multiple patient-reported outcomes (including those that address fatigue), objective physical functioning, biologic correlative markers (including assessment of the insulin pathway), and an economic analysis. Current Enrollment: The study is open at 19 centers in Canada and 20 centers in Australia. Accrual as of February 4, 2013 includes 212 registered and 184 randomized patients. Summary: Cancer survivors and cancer care professionals are interested in the potential role of PA to improve multiple disease-related outcomes, but a randomized controlled trial is needed to provide compelling evidence to justify changes in health care policies and practice. Clinical trial information: NCT00819208.

scholarly journals ProCare Trial: a phase II randomized controlled trial of shared care for follow-up of men with prostate cancer

2016 ◽  
Vol 119 (3) ◽  
pp. 381-389 ◽  
Author(s):  
Jon D. Emery ◽  
Michael Jefford ◽  
Madeleine King ◽  
Dickon Hayne ◽  
Andrew Martin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Randomized Controlled Trial ◽  
Phase Ii ◽  
Controlled Trial ◽  
Shared Care ◽  
Randomized Controlled

A secondary analysis of PSA response in NRG Oncology/RTOG 9902: A phase III trial of adjuvant chemotherapy with androgen suppression and radiation for high-risk prostate cancer (CaP).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5078-5078
Author(s):  
Stephen Andrew Mihalcik ◽  
Meredith M. Regan ◽  
Seth A. Rosenthal ◽  
Glenn J. Bubley ◽  
Kenneth J. Pienta ◽  
...  
Keyword(s):  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Controlled Trial ◽  
Secondary Analysis ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Treatment Intensification ◽  
High Risk Prostate Cancer ◽  
Androgen Suppression

5078 Background: RTOG 9902 was a randomized controlled trial of the addition of adjuvant chemotherapy (CT; paclitaxel, oral etoposide, and estramustine x4 cycles) to 24 mo of androgen suppression (AS) and radiation (RT) for patients (pts) with high-risk CaP., beginning with an initial 4 mo of AS; RT began after 2 mo. 9902 accrued 397 pts and closed early due to excess toxicity. At a median follow-up of 9.2 years, there was no benefit to CT, but it is hypothesized that a subset analysis by post-RT PSA identifies pts that benefit from treatment intensification with CT. Methods: Post-RT PSA status was dichotomized at > 0.2 ng/mL within 1 mo of RT. Landmark analysis redefined starting times for disease-free survival (DFS), time to distant metastasis (TDM) and overall survival (OS) at 16 weeks post-RT (36 weeks post-randomization) when CT was planned to complete. Pts were excluded if they did not get RT or assigned CT, or experienced DFS events/lost to follow-up < 36 wks post-randomization. Hazard ratios (HR), 95% confidence intervals (CI), and PSA-by-treatment interaction were estimated by Cox or competing-risks regression. Results: 333 pts were analyzed: 190 without and 143 with CT. 37% of pts had a post-RT PSA ≤0.2, 34% > 0.2, and 29% no recorded PSA in the defined interval. CT was associated with improved DFS for pts with PSA > 0.2 (HR 0.59, 0.38-0.91), but not for those with PSA ≤0.2 (HR 0.94, 0.60-1.46; interaction p = 0.13). This association, for those with PSA > 0.2, persisted in those pts who received the full course of CT and trended in the same direction for pts receiving 1-3 cycles. CT was associated with a trend toward improved TDM in the PSA > 0.2 group (HR 0.56, 0.23-1.35) and not in the PSA≤0.2 group (HR 1.31, 0.36-4.70), based on 32 pts with metastases. OS did not show the same pattern (PSA > 0.2: HR 0.98, 0.55-1.77; PSA≤0.2: HR 0.57, 0.29-1.13). Conclusions: This analysis suggests that men with high-risk CaP and suboptimal response to AS+RT, as identified by post-RT PSA > 0.2, may benefit from adjuvant CT. Prospective trials using contemporary CT (e.g. docetaxel) will help optimize treatment for these men. NRG-GU002, recently activated, is addressing this issue.

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