Randomized Trial of Postoperative Adjuvant Therapy in Stage II and III Rectal Cancer to Define the Optimal Sequence of Chemotherapy and Radiotherapy: 10-Year Follow-Up

2011 ◽  
Vol 81 (4) ◽  
pp. 1025-1031 ◽  
Author(s):  
Tae-Won Kim ◽  
Je-Hwan Lee ◽  
Jung-Hee Lee ◽  
Jin-Hee Ahn ◽  
Yoon-Koo Kang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Therapy ◽  
Randomized Trial ◽  
Stage Ii ◽  
Postoperative Adjuvant Therapy ◽  
Optimal Sequence

Randomized trial of postoperative adjuvant therapy in stage II and III rectal cancer to define the optimal sequence of chemotherapy and radiotherapy: A final report

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4050-4050
Author(s):  
T. Kim ◽  
J. Lee ◽  
J. Lee ◽  
K. Lee ◽  
Y. Kang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Randomized Trial ◽  
Statistical Significance ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Chemotherapy Cycle ◽  
Final Report ◽  
Optimal Sequence ◽  
Radiotherapy Group

4050 Background: We conducted a prospective randomized trial to define the optimal sequence of chemotherapy and radiotherapy of postoperative adjuvant treatment in stage II and III rectal cancer. Methods: Three hundred eight patients were enrolled onto the study. We randomly assigned 155 to arm I (early radiotherapy group) and 153 to arm II (late radiotherapy group). Treatment included eight cycles of chemotherapy at 4-week intervals and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on day 1 of the first chemotherapy cycle in arm I and on day 1 of the third chemotherapy cycle in arm II. The chemotherapy regimen consisted of fluorouracil 375 mg/m2/d and leucovorin 20 mg/m2/d. Chemotherapy was administered for 3 days per cycle in two cycles during the period of radiotherapy and for 5 days per cycle in the remaining six cycles. (J Clin Oncol 2002 20:1751- 8) Results: Twenty patients in arm I and 14 in arm II were not eligible. We included 274 patients in the analysis. With a median follow-up of 94 months for surviving patients, there was a trend for improved disease-free survival(DFS) in arm I compared with arm II, although it was not reached statistical significance (72% v. 63% at 7 years; P =.157). Especially, in patients who received abdominoperineal resection (APR), DFS was prolonged in arm I compared with arm II (66% v. 41% at 7 years; P=.033) Thirty six recurrences (26.7%) occurred in arm I and 49 (35.3%) in arm II (P =.151). Overall survival was not significantly different between arms I and II (71% v. 68% at 7 years; P =.855). Conclusions: With a long-term follow-up, this study failed to show a significant survival advantage for early radiotherapy with concurrent chemotherapy after resection of stage II and III rectal cancer. In patients with APR, significant improvement in DFS for arm I was observed. No significant financial relationships to disclose.

Randomized Trial of Postoperative Adjuvant Therapy in Stage II and III Rectal Cancer to Define the Optimal Sequence of Chemotherapy and Radiotherapy: A Preliminary Report

2002 ◽  
Vol 20 (7) ◽  
pp. 1751-1758 ◽  
Author(s):  
Jung-Hee Lee ◽  
Je-Hwan Lee ◽  
Jin-Hee Ahn ◽  
Hyeseung Bahng ◽  
Tae-Won Kim ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Randomized Trial ◽  
Group Treatment ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Chemotherapy Cycle ◽  
Optimal Sequence ◽  
Free Survival ◽  
Radiotherapy Group ◽  
Disease Free

PURPOSE: We conducted a prospective randomized trial to define the optimal sequence of chemotherapy and radiotherapy of postoperative adjuvant treatment in stage II and III rectal cancer. PATIENTS AND METHODS: Three hundred eight patients were enrolled onto the study. We randomly assigned 155 to arm I (early radiotherapy group) and 153 to arm II (late radiotherapy group). Treatment included eight cycles of chemotherapy at 4-week intervals and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on day 1 of the first chemotherapy cycle in arm I and on day 1 of the third chemotherapy cycle in arm II. The chemotherapy regimen consisted of fluorouracil 375 mg/m2/d and leucovorin 20 mg/m2/d. Chemotherapy was administered for 3 days per cycle in two cycles during the period of radiotherapy and for 5 days per cycle in the remaining six cycles. RESULTS: Twenty patients in arm I and 14 in arm II were not eligible. We included 274 patients in the analysis. With a median follow-up of 37 months for surviving patients, disease-free survival was significantly prolonged in arm I compared with arm II (81% v 70% at 4 years; P = .043). Twenty-three recurrences occurred in arm I and 38 in arm II (P = .047). Overall survival was not significantly different between arms I and II (84% v 82% at 4 years; P = .387). CONCLUSION: Early radiotherapy with concurrent chemotherapy after resection of stage II and III rectal cancer demonstrated a statistically significant advantage for disease-free survival compared with late radiotherapy with chemotherapy.

A randomized trial of levamisole versus placebo as adjuvant therapy in malignant melanoma.

1991 ◽  
Vol 9 (5) ◽  
pp. 736-740 ◽  
Author(s):  
L E Spitler
Keyword(s):  
Malignant Melanoma ◽  
Adjuvant Therapy ◽  
Randomized Trial ◽  
Control Groups ◽  
Disease Free Interval ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
And Control

We conducted a long-term follow-up (median, 10.5 years) of patients included in a randomized trial of levamisole versus placebo as surgical adjuvant therapy in 203 patients with malignant melanoma. Of the patients randomized, 104 received levamisole, and 99 received placebo. The results show that there is no difference between the treatment and control groups with regard to any of the three end points analyzed. These included disease-free interval, time to appearance of visceral metastasis, and survival. Moreover, there was no significant difference between the treatment and control groups after adjusting for age, sex, or stage of disease.

Randomized trial of chemoendocrine therapy started before or after surgery for treatment of primary breast cancer.

1995 ◽  
Vol 13 (3) ◽  
pp. 547-552 ◽  
Author(s):  
T J Powles ◽  
T F Hickish ◽  
A Makris ◽  
S E Ashley ◽  
M E O'Brien ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Adjuvant Therapy ◽  
Randomized Trial ◽  
Response Rate ◽  
Neoadjuvant Treatment ◽  
Operable Breast Cancer ◽  
Chemoendocrine Therapy ◽  
Primary Operable Breast Cancer

PURPOSE To evaluate in a randomized clinical trial systemic chemoendocrine therapy used as primary (neo-adjuvant) treatment before surgery in women with primary operable breast cancer. PATIENTS AND METHODS Patients aged less than 70 years with clinically palpable, primary operable breast cancer diagnostically confirmed by fine-needle aspiration cytology (FNAC) and suitable for treatment with surgery, radiotherapy, cytotoxic chemotherapy, and tamoxifen were considered eligible. Patients randomized to neoadjuvant treatment received four cycles of chemo-therapy for 3 months before surgery followed by another four cycles after surgery, and were compared with patients randomized to adjuvant therapy who received eight cycles of chemotherapy over 6 months after surgery. RESULTS Of 212 patients who were randomized to receive either adjuvant (n = 107) or neoadjuvant (n = 105) chemoendocrine therapy, 200 are now assessable for response. The two groups are comparable for age, menopausal status, disease stage, and surgical requirements. The overall clinical response rate was 85%, with a complete histologic response rate of 10%. There was a significant reduction in the requirement for mastectomy in patients who received neoadjuvant treatment (13%) as compared with those who received adjuvant therapy (28%) (P < .005). Symptomatic and hematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy. The median follow-up period for patients in this trial is 28 months, during which time four patients have relapsed locally and 20, including one of the local relapses, have developed metastatic disease, 19 of whom have died. The follow-up period is too brief to evaluate relapse rate or survival duration. CONCLUSION This trial confirms previous reports of a high rate of response to neoadjuvant therapy, but is the first to include small primary cancers and to show, in the context of a randomized trial, a reduction in the requirement for mastectomy. Until disease-free and overall survival data are available from the larger National Surgical Adjuvant Breast and Bowel Project (NSABP)-18 trial, such neoadjuvant treatment cannot be recommended outside of a clinical trial.

Validation of a genomic classifier (ColoPrint) for predicting outcome in the T3-MSS subgroup of stage II colon cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3510-3510 ◽  
Author(s):  
Ramon Salazar ◽  
Josep Tabernero ◽  
Victor Moreno ◽  
Ulrich Nitsche ◽  
Thomas Bachleitner-Hofmann ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Cancer Patients ◽  
Lower Risk ◽  
Low Risk ◽  
Stage Ii ◽  
Disease Relapse ◽  
Risk Of Disease

3510 Background: Adjuvant therapy for stage II patients is recommended for patients with high risk features, especially with T4 tumors. Adjuvant therapy is not indicated for patients with MSI-H status who are considered of being at low risk of disease relapse. However, this leaves the majority of patients with an undetermined risk. ColoPrint is an 18-gene expression classifier that identifies early-stage colon cancer patients at higher risk of disease relapse. Methods: ColoPrint was developed using whole genome expression data and was validated in public datasets (n=322) and independent patient cohorts from 5 European hospitals. Tissue specimen, clinical parameters, MSI-status and follow-up data (median follow-up 70 months) for patients were available and the ColoPrint index was determined using validated diagnostic arrays. Uni-and multivariate analysis was performed on the pooled stage II patient set (n=320) and the subset of patients who were T3/ MSS (n=227). Results: In the analysis of all stage II patients, ColoPrint classified two-third of stage II patients as being at lower risk. The 3-year Relapse-Free-Survial (RFS) RFS was 91% for Low Risk and 74% for patients at higher risk with a HR of 2.9 (p=0.001). Clinicopathological parameters from the ASCO recommendations (T4, perforation, <12 LN assessed, and/ or high grade) or NCCN guidelines (ASCO factors plus angio-lymphatic invasion) did not predict a differential outcome for high risk patients (p< 0.20). In the subgroup of patients with T3 and MSS phenotype, ColoPrint classified 61% of patients at lower risk with a 3-year RFS of 91% (86-96%) and 39% of patients at higher risk with a 3-year RFS of 73% (63-83%) (p=0.002). No clinical parameter was significantly prognostic in this subgroup. Conclusions: ColoPrint combined with established clinicopathological factors and MSI, significantly improves prognostic accuracy, thereby facilitating the identification of patients at higher risk who might be considered for additional treatment.

Cohort study evaluating the impact of a discharge letter (DL) compared with usual care on adherence to surveillance following treatment for stage II/III colorectal cancer (CRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 620-620 ◽  
Author(s):  
Janine Marie Davies ◽  
Eugene Batuyong ◽  
Sasha M. Lupichuk ◽  
Robert Hilsden ◽  
Misha Eliasziw ◽  
...  
Keyword(s):  
Cohort Study ◽  
Adjuvant Therapy ◽  
Clinical Laboratory ◽  
Ct Imaging ◽  
Care Physician ◽  
Stage Ii ◽  
Disease Stage ◽  
Cancer Centre ◽  
The Impact

620 Background: The 2005 ASCO guidelines recommend surveillance testing and frequencies following surgical +/− adjuvant therapy for stage II/III CRC. In Canada, many patients are discharged from their oncologist to their primary care physician (PCP) for ongoing surveillance. However, adherence to surveillance recommendations is low. This cohort study evaluated adherence to surveillance 1 year after treatment of stage II/III CRC prior to and following implementation of a DL. Methods: Cohort 1 (C1) patients were retrospectively identified from the Alberta Cancer Registry following adjuvant therapy (as applicable) at a tertiary cancer centre (07/2006 - 09/2007). Cohort 2 (C2) patients were prospectively identified from the Registry and clinic records following adjuvant therapy (as applicable), as those discharged from the centre (10/2007 - 4/2009); DL was sent to the patient and PCP recommending surveillance tests and dates. Clinical, laboratory, diagnostic imaging, and endoscopy data was collated. Adherence at 1 year follow-up was compared between cohorts using Kaplan-Meier time-to-event analyses. Results: C1 (n=218) was larger than C2 (n=114) despite the longer accrual time for C2. There were no differences between cohorts by age, sex, primary site of disease, stage, or adjuvant oxaliplatin use. During year 1 of follow-up, 11.8% and 11.4% recurred (local or metastatic) and 6.5% and 2.7% died (p=0.1) in C1 and C2 respectively. Comparing C1 with C2, 14.8% vs. 23.0% of patients had one CEA test within 3 months, 45.2% vs. 72.2% within 6 months, and 71.7% vs. 85.1% within 1 year (p<0.001). Only 44.0% (C1) and 68.6% (C2) had 2 CEA tests within 1 year. Only 3.9% (C1) vs. 6.6% (C2) of patients had 4 CEA tests within the year following treatment as recommended. The rate of CT imaging was 32.3% (C1) and 56.1% (C2); endoscopy was 36.7% (C1) and 42.1% (C2). Conclusions: Implementation of a DL improved compliance with surveillance at 1 year of follow-up following discharge from a tertiary cancer centre, although optimal adherence remains low. However, adherence to CT imaging nearly doubled. Evaluation of compliance at 3 years of follow-up is ongoing.

Intergroup randomized phase III study of postoperative irinotecan, 5-fluorouracil, and leucovorin versus oxaliplatin, 5-fluorouracil, and leucovorin versus 5-fluorouracil and leucovorin for patients with stage II or III rectal cancer receiving either preoperative radiation and 5-fluorouracil or postoperative radiation and 5-fluorouracil: ECOG E3201—An updated survival analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14711-e14711 ◽  
Author(s):  
Halla Sayed Nimeiri ◽  
Yang Feng ◽  
Paul J. Catalano ◽  
Neal J. Meropol ◽  
Bruce J. Giantonio ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Therapy ◽  
Small Sample Size ◽  
Anal Verge ◽  
Single Agent ◽  
Data Monitoring Committee ◽  
Small Sample ◽  
Stage Ii ◽  
Phase Iii ◽  
Preoperative Radiation

e14711 Background: Postoperative adjuvant chemotherapy has been historically limited to single agent 5FU in stage II/III rectal cancer pts. This phase III trial evaluated differences between pts treated with adjuvant FOLFOX versus FOLFIRI versus FU alone in stage II/III rectal cancer. Methods: Eligibility: resectable (T3-4 N0,Tany N1-3) adenocarcinoma rectum ≤12cm from anal verge. Pts had the option to receive FU with pre or postoperative XRT (50.4Gy). Preoperative FU/XRT pts were randomized to adjuvant FOLFIRI (arm A), FOLFOX (arm B), FU/LV(arm C). Postoperative FU/XRT pts were randomized to adjuvant FOLFIRI (arm D), FOLFOX (arm E), FU/LV (arm F). Pts received 8 cycles. Overall survival (OS) was the primary endpoint. Secondary endpoints included toxicity, sphincter preservation and patterns of failure. Results: 225pts out of planned 3150 were enrolled (10/03 to 10/05). Data Monitoring Committee closed E3201 when the GI Intergroup developed an alternative trial with bevacizumab (E5204). 179 pts were randomized; (A:28, B:25, C:30, D:31, E:33, F:32). There was increased grade 3/4 toxicity, mainly diarrhea,in postoperative FU/XRT arms (D:39%), (E:28%), (F:48%). Twenty-two (12%) pts did not receive adjuvant therapy. At a median follow up of 7.4yrs, the five-year recurrence free rate was 69%. Median OS was 8.3 yrs. There was no statistical difference in OS between all randomized groups. Five-year OS in arms (A:B:C:D:E:F) were (73%, 83%, 83%, 73%, 78%, 73%) respectively. Conclusions: FOLFOX can be safely administered to rectal cancer pts following chemo radiation. Given limitations of early trial closure and small sample size, there was no difference in OS between pts who received FU alone, oxaliplatin based or irinotecan based adjuvant therapy. Clinical trial information: NCT00068692.

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