5FU/LV with or without irinotecan in patients with resected stage II-III rectal cancer: Final analysis of R98 intergroup study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3542-3542
Author(s):  
Catherine Delbaldo ◽  
Marc Ychou ◽  
Ayman Zawadi ◽  
Jean-Yves Douillard ◽  
Thierry André ◽  
...  

3542 Background: The goal of the study was to test whether adding Irinotecan to a 5-FU/LV adjuvant regimen improves disease free survival (DFS) or overall survival (OS) in optimally resected stages II-III rectal cancers. Primary end-point was DFS. Methods: Six hundred patients were planned to be randomized between 5-FU/LV (control arm) or 5-FU/LV + irinotecan (experimental arm). As only 357 patients had been included from 03/1999 to 12/2005 (178 in control and 179 in experimental arm), the IDMC recommended to close accrual. The trial was stratified by control arm: Mayo-Clinic regimen (A: LV 20 mg/m², 5-FU 425 mg/m² bolus days (d) 1- 5 reapeted at d29,57,92,127 and 162) or LV5-FU2 regimen (A’: LV 200 mg/m², 5-FU 400 mg/m² bolus and 5-FU 600 mg/m² 22-hours infusion d1-2, q 2 w for 12 cycles). The experimental arm (B) was LV5-FU2 + irinotecan 180 mg/m² d1. Results: All 357 randomized patients were evaluable for efficacy. Patient characteristics were well balanced (median age 62 years, stage II 31 %, stage III 69 %, N0 31 %, 68 % received preoperative radiotherapy, and 80 % had sphincter conservation). With follow-up of 156 months, DFS and OS are not statistically increase (81vs 92 events for DFS in experimental and control arm, hazard ratio (HR)=0.805, p=0.154;63 vs 72 events for OS, HR=0.874, p=0.433). Patients allocated to the experimental arm had more grade 3-4 neutropenia when compared with the LV5FU2 control (33 % vs 16 %, p=0.03), but not when compared with the Mayo Clinic arm (32% vs 36%, p=0.84). Grade 3-4 diarrhea tend to be higher in the experimental arm, but analyses stratified by control arm or by radiotherapy failed to show significant differences across strata (test for interaction p=0.44). Conclusions: In patients with resected stage II-III rectal cancer, adding irinotecan to 5FU/LV led to a non significant increase of DFS and OS. The analysis was planned to have a 60 % power to detect a significant difference with 220 events. With a long term follow up of 8 years only 173 events were observed in our trial. Lack of power and good patient prognosis (thirty one percent of node negative patients) may have impacted the results.

2003 ◽  
Vol 21 (15) ◽  
pp. 2896-2903 ◽  
Author(s):  
Thierry André ◽  
Philippe Colin ◽  
Christophe Louvet ◽  
Erik Gamelin ◽  
Olivier Bouche ◽  
...  

Purpose: This randomized, 2 × 2 factorial study compared a semimonthly (LVFU2) with a monthly (FULV) regimen of fluorouracil and leucovorin and 24 versus 36 weeks of each regimen as adjuvant treatment of patients with stage II (Dukes’ B2) and III (Dukes’ C) colon cancer. Patients and Methods: LVFU2 was administered semi-monthly for 2 consecutive days as dl- or l-leucovorin (200 or 100 mg/m2, respectively) as a 2-hour infusion, followed by a 400 mg/m2 FU bolus and 600 mg/m2 of FU as a 22-hour continuous infusion. FULV was administered monthly for 5 consecutive days as a 15-minute infusion of dl- or l-leucovorin, followed by 400 mg/m2 of FU as a 15-minute infusion. Results: A total of 905 patients were randomly assigned. The median follow-up was 41 months. Disease-free survival was similar between the LVFU2 and FULV groups (127 v 124 events; hazard ratio [HR] = 1.04; P = .74) and between 24 and 36 weeks of therapy (128 v 123 events; HR = 0.94; P = .63). Analysis of overall survival showed a slight excess in the number of deaths in LVFU2 compared with FULV (73 v 59), but this difference was not statistically significant (HR = 1.26; 95% confidence interval, 0.90 to 1.78; P = .18). The most commonly observed grade 3 to 4 toxicities were neutropenia, diarrhea, and mucositis. Toxicities were significantly lower in the LVFU2 group (all toxicities, P < .001). Conclusion: Our data confirm that LVFU2 is less toxic than FULV. At a median follow-up of 41 months, no statistically significant difference could be detected in disease-free or overall survival between the treatment groups or treatment durations.


1992 ◽  
Vol 59 (1_suppl) ◽  
pp. 160-162
Author(s):  
◽  
Urologico Lombardo

In February 1990, a multicentric randomized study was started to verify the therapeutic efficacy of adjuvant alpha-interferon in Robson's stage II and III renal cell carcinoma. Up to April 1992, 749 radical nephrectomies have been recorded by the 25 participating centers. Stage II and III patients fullfilling selection criteria were 124: 64 were assigned to Interferon therapy and 60 to control. The short follow-up does not allow any evaluation of the relapse rate. Therapy related toxicity was represented by mild fever and flu-like syndrome in 50% of cases and slight leucopenia in 5%. The recruitment of the first 200 randomized patients will end approximately within 1 year. While evaluating the hypothesis of a 20% difference in the 5 year disease-free survival between the two groups recruitment will continue up to a total of 350 cases, in order to verify the 15% hypothesis, too.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4007-4007 ◽  
Author(s):  
A. de Gramont ◽  
C. Boni ◽  
M. Navarro ◽  
J. Tabernero ◽  
T. Hickish ◽  
...  

4007 Background: The MOSAIC study was designed to evaluate the effects of the FOLFOX4 regimen (5-FU/LV + oxaliplatin) on 3- year disease free survival (DFS) probability in patients with stage II and III colon cancer. Methods: Patients (n=2246) with completely resected stage II (40%) or III (60%) colon cancer were randomly assigned to receive 5-FU/LV (LV5FU2) or FOLFOX4 every 2 weeks for 12 cycles. Results: Results for the primary endpoint of the study (for the overall population, with a median follow-up [FU] of 3 years), showed a significant benefit in DFS for the FOLFOX4-treated patients (78.2% vs 72.9%; HR: 0.77, p=0.002) (André et al, NEJM, 2004). Patients were followed beyond the 3-year cut-off for DFS and overall survival (OS) updates. Final DFS, at 5 years FU, are consistent with earlier results (HR: 0.80, p = 0.003). In addition, at a median FU of 6 years, the study demonstrates a significant benefit in OS for the stage III patients. Summary of OS results (median FU 6 years) Long-term safety update shows no increase in the rate of secondary cancer (5.0% in both treatment arms). Conclusions: These results confirm the benefit of the FOLFOX4 regimen in adjuvant colon cancer patients. [Table: see text] No significant financial relationships to disclose.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 516-516 ◽  
Author(s):  
J. A. Sparano ◽  
M. Wang ◽  
S. Martino ◽  
V. Jones ◽  
E. Perez ◽  
...  

516 Background: Evidence suggests that docetaxel is more effective than paclitaxel, and paclitaxel is more effective when given weekly than every 3 weeks in metastatic breast cancer (BC). Methods: Eligibility included axillary lymph node positive or high-risk (tumor at least 2 cm) node-negative BC. All patients received 4 cycles of AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks, followed by either: (1) paclitaxel 175 mg/m2 every 3 weeks × 4 (P3), (2) paclitaxel 80 mg/m2 weekly × 12 (P1), (3) docetaxel 100 mg/m2 every 3 weeks × 4 (D3), or (4) docetaxel 35 mg/m2 weekly × 12 (D1). The primary comparisons included taxane (P vs. D) and schedule (every 3 weeks vs. weekly), and secondary comparisons included P3 vs. other arms. The trial had 86% power to detect a 17.5% decrease in disease-free survival (DFS) for either primary comparison, and 80% power to detect a 22% decrease for the secondary comparisons (2-sided nomimal 5% level tests corrected for multiple comparisons). Results: A total of 4,950 eligible patients were accrued. There was no difference in the primary comparisons afer 856 DFS events and 483 deaths after a median follow-up of 46.5 months at the 4th interim analysis ( www.sabcs.org , abstract 48). This is the final pre-specified analysis for the primary comparisons after 1,042 DFS events and 650 deaths (with 1,020 DFS events at this time, to be updated at the meeting). After a median followup of 60.2 months, there remains no significant difference in the hazard ratio (HR) for the taxane (1.02; p=0.73) or schedule (1.07; p=0.30) (as in the first analysis). In secondary comparisons of the standard arm (P3) with the other arms (HR > 1 favoring the experimental arms), the HRs were 1.30 (p = 0.003) for arm P1, 1.24 (p=0.02) for arm D3, and 1.09 (p=0.33) for arm D1. Analysis of interaction by hormone-receptor status will be presented. The incidence of worst grade toxicity (grade 3/4) was 24%/6% for arm P3, 24%/3% for arm P1, 21%/50% for arm D3, and 38%/6% for arm D1. Conclusions: There were no differences in DFS when comparing taxane or schedule overall. DFS was significantly improved in the weekly paclitaxel and every 3-week docetaxel arms compared with the every 3-week paclitaxel arm. [Table: see text]


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4049-4049 ◽  
Author(s):  
T. Hamaguchi ◽  
K. Shirao ◽  
Y. Moriya ◽  
S. Yoshida ◽  
S. Kodaira ◽  
...  

4049 Background: In the latter 1990s, no consensus was reached as to whether adjuvant chemotherapy was standard treatment for completely resected stage III colorectal cancer in Japan. At that time, we started two randomized controlled trials to clarify the role of adjuvant chemotherapy of stage III colon and rectal cancer in the same time. Methods: Patients with completely resected stage III cancer of the colon or rectum (PS, 0 to 2; age, 20 to 75 years; no other adjuvant therapy) were eligible for these trials. Patients were registered within 6 weeks after surgery and were randomly assigned to receive surgery alone (control group) or surgery followed by treatment with UFT (400 mg/m2/day), given for 5 consecutive days per week for 1 year (UFT group). The target number of patients was 500 for colon cancer and 400 for rectal cancer (hazard ratio = 0.67, one-sided a= 0.05, β= 0.2). The primary endpoint was relapse-free survival (RFS), and the secondary end point was overall survival (OS). Results: Between October 1996 and April 2001, a total of 334 patients with colon cancer and 276 with rectal cancer were enrolled. Four ineligible patients were excluded; data from the remaining 332 patients with colon cancer and 274 with rectal cancer were analyzed. The patients’ characteristics were similar in the groups. Analysis of the results of follow-up until March 2006, at least 5 years after surgery in all patients (median follow-up period, 6.2 years), showed no significant difference in RFS or OS in colon cancer. In rectal cancer, however, RFS and OS were significantly better in the UFT group than in the control group. The only grade 4 toxicity was diarrhea, occurring in 1 patient with colon cancer and 1 patient with rectal cancer. Conclusions: Postoperative adjuvant chemotherapy with UFT is well tolerated and improved RFS and OS in patients with stage III rectal cancer. In colon cancer, the expected benefits were not obtained (hazard ratio = 0.67). [Table: see text] No significant financial relationships to disclose.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 408-408
Author(s):  
Cynthia Harris ◽  
Michelle Kang Kim ◽  
Kiwoon Joshua Baeg ◽  
Mi Ri Lee ◽  
Julie Starr ◽  
...  

408 Background: Current surveillance guidelines regarding follow up of patients with resected pancreatic neuroendocrine tumors (PNETs) are based on limited data, and there have been few studies evaluating recurrence risk in such patients. We assessed disease-free survival (DFS) in a large, multi-institutional cohort of patients with resected PNETs. Methods: Patients with surgically resected, non-metastatic PNETs between 1990-2017 were identified using institutional databases at three institutions: Mount Sinai Hospital, Dana-Farber Cancer Institute, and University of Pennsylvania. Recurrence date was defined as the imaging date documenting first recurrence (n = 56); if an imaging date was not available, then July 1 of that year was used in calculations (n = 9). Kaplan-Meier analysis was used to estimate DFS; multivariate Cox regression analysis was used to assess DFS adjusted for patient and disease-related characteristics, including tumor stage and grade. Results: We identified a total of 418 patients with surgically resected, non-metastatic PNETs between 1990-2017. Of these patients, 299 patients had complete stage and tumor grade information and were used for subsequent analysis. Patients were 48.6% male with a median age of 57.5 years at time of surgery. The distribution of AJCC stage and grade was as follows: 170 (56.9%) patients were stage I, 129 (43.1%) were stage II; 167 (55.9%) had grade 1, 121 (40.5%) had grade 2, and 11 (3.7%) had grade 3 tumors. Median follow-up was 2.6 years (interquartile range = 4.2); during this time, 65 (21.7%) patients developed disease recurrence. After adjusting for potential confounders, patients with more advanced stage and higher tumor grade were significantly more likely to develop disease recurrence (Hazard Ratio (HR): 6.9, 95% CI: 2.5-19.1 for stage II; HR 4.0 (1.7-9.5) for grade 2; HR 2.6 (0.4-17.8) for grade 3). Both higher stage and tumor grade were associated with decreased DFS (p < 0.0001 for both). Conclusions: In surgically resected PNETs, with a median follow-up time of 2.6 years, both higher stage and higher grade are associated with decreased DFS. Further follow up of this cohort is planned.


2020 ◽  
pp. 1639-1646
Author(s):  
Muhammad Atif Mansha ◽  
Tabinda Sadaf ◽  
Asmara Waheed ◽  
Amna Munawar ◽  
Asma Rashid ◽  
...  

PURPOSE To report the chronic toxicity and disease outcomes attributable to intensity-modulated radiation therapy (IMRT) in patients with cervical cancer. METHODS AND MATERIALS Between January 2014 and December 2018, a retrospective review of medical records of patients with cervical cancer who received radiation therapy with IMRT was performed. Disease and treatment-related details were documented. Follow-up notes were reviewed, and severity of late toxicities was recorded. Overall survival (OS) and disease-free survival (DFS) at 3 years were estimated. RESULTS A total of 222 patients’ records were reviewed. Mean age was 50.7 years. Median follow-up duration was 33 months (range, 2-70 months). The most common toxicity was vaginal stricture (grade 2, n = 59, 26.6%; grade 3, n = 4, 1.80%), followed by proctitis (grade 2, n = 24; 10.8%; grade 3, n = 7; 3.20%). Seven patients (grade 2, n = 5, 2.3%; grade 3, n = 2; 0.90%) developed cystitis, and only 5 (grade 2; 2.3%) were found to have colitis. None of the patients had grade 4 or grade 5 toxicities. There was a significant difference in late complications in patients with nodal disease or those who underwent prior surgery ( P < .05). Three-year OS and DFS rates were 79.7% and 81.9%, respectively. Patients with tumor size > 5 cm and those with pelvic lymph node metastasis had poor survival rates ( P < .05). CONCLUSION IMRT is an effective and well-tolerated technique that should be considered in patients with lymph node disease and in postoperative patients. There is an inverse relationship between tumor size and nodal involvement with respect to OS and DFS.


2007 ◽  
Vol 25 (16) ◽  
pp. 2198-2204 ◽  
Author(s):  
J. Philip Kuebler ◽  
H. Samuel Wieand ◽  
Michael J. O'Connell ◽  
Roy E. Smith ◽  
Linda H. Colangelo ◽  
...  

Purpose This phase III clinical trial evaluated the impact on disease-free survival (DFS) of adding oxaliplatin to bolus weekly fluorouracil (FU) combined with leucovorin as surgical adjuvant therapy for stage II and III colon cancer. Patients and Methods Patients who had undergone a potentially curative resection were randomly assigned to either FU 500 mg/m2 intravenous (IV) bolus weekly for 6 weeks plus leucovorin 500 mg/m2 IV weekly for 6 weeks during each 8-week cycle for three cycles (FULV), or the same FULV regimen with oxaliplatin 85 mg/m2 IV administered on weeks 1, 3, and 5 of each 8-week cycle for three cycles (FLOX). Results A total of 2,407 patients (96.6%) of the 2,492 patients randomly assigned were eligible. Median follow-up for patients still alive is 42.5 months. The hazard ratio (FLOX v FULV) is 0.80 (95% CI, 0.69 to 0.93), a 20% risk reduction in favor of FLOX (P < .004). The 3- and 4-year disease-free survival (DFS) rates were 71.8% and 67.0% for FULV and 76.1% and 73.2% for FLOX, respectively. Grade 3 neurosensory toxicity was noted in 8.2% of patients receiving FLOX and in 0.7% of those receiving FULV (P < .001). Hospitalization for diarrhea associated with bowel wall thickening occurred in 5.5% of the patients receiving FLOX and in 3.0% of the patients receiving FULV (P < .01). A total of 1.2% of patients died as a result of any cause within 60 days of receiving chemotherapy, with no significant difference between regimens. Conclusion The addition of oxaliplatin to weekly FULV significantly improved DFS in patients with stage II and III colon cancer. FLOX can be recommended as an effective option in clinical practice.


2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Lauren O'Connell ◽  
Sinead Ramjit ◽  
Tim Nugent ◽  
Paul Neary ◽  
Adnan Hafeez ◽  
...  

Abstract Background Robotic-assisted minimally invasive surgery (MIS) for rectal cancer is a relatively new technique. Studies to date suggest that short term outcomes including TME quality, margin status, lymph node retrieval and 30-day morbidity and mortality are equivalent in robotic-assisted and laparoscopic MIS for rectal cancer. By contrast, there is a paucity of data on the medium and long-term oncologic safety of robotic-assisted comparative to laparoscopic surgery for rectal cancer. Methods A retrospective review was conducted of all robotic-assisted (n = 31) and laparoscopic (n = 23) rectal cancer cases performed at our institution between January 2016 to December 2018. Inclusion criteria were patients scheduled electively for a laparoscopic or robotic-assisted resection of rectal cancer (anterior resection or abdomino-perineal resection). Patients with distant metastases at presentation, those who proceeded to surgery as an emergency and those with a non-colorectal primary were excluded from analysis. Results A total of 54 (n = 54) cases met the inclusion criteria and were included in the final analysis. The median follow-up was 34 months. Of the 54, 21 patients received neoadjuvant chemoradiotherapy prior to definitive surgery. No significant difference was detected in local recurrence rates (p = 0.5), overall survival (p = 0.7) or disease-free survival (p = 0.8) between the robotic-assisted and laparoscopic cohorts. Conclusion In this series, robotic-assisted rectal cancer resections were associated with equivalent medium term oncological outcomes as laparoscopic procedures. However, given the small numbers in this cohort, outcomes from larger scale datasets will be required to confirm these results.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3586-3586
Author(s):  
Darren Cowzer ◽  
Emily Harrold ◽  
Jane Sze Yin Sui ◽  
Mairi Lucas ◽  
Helen M Fenlon ◽  
...  

3586 Background: Mucinous colorectal cancer (CRC) differs from adenocarcinoma with regard to clinical and histological features and is reported to have inferior outcomes when compared to non-mucinous CRC. This study aims to evaluate the clinical features and outcomes of patients with mucinous CRC at our institution. Methods: Medical records of patients with CRC that were referred to medical oncology between September 1999 and September 2018 were retrospectively reviewed. Mucinous histology was defined as those containing > 50% mucin identified on histology specimens. Statistical analysis was performed using Prism V9.0. Results: We identified 1,115 patients with CRC that were referred to medical oncology during this period. The tumours of 81 (7.3%) patients were classified as mucinous. Median age was 65 (28-94 years) and 45 (55.5%) were male. Forty-one patients (51%) had right sided tumours, 27 (33%) had left sided tumours and 13 (16%) had rectal tumours. Twenty-three (28.4%) had de novo metastatic disease. Eleven of 24 patients (46%) with stage II disease relapsed and 18 of 33 (55%) of those with stage III disease relapsed. Radiological surveillance identified 20/29 (69%) of relapsed disease, 5 (17%) were symptomatic and 4 (14%) had a rise in CEA. Median follow up for patients with stage II disease was 53 months and 3 year and 5-year disease free survival (DFS) was equal in both groups at 60.9%. For stage III disease 3- and 5-year DFS was 58.1% and 48.4% respectively with a median follow up of 43 months. In the metastatic setting, we observed no significant difference in overall survival (OS) between left and right sided tumours ( p = 0.550). Median OS for pts with stage IV mucinous CRC who received any treatment was 25 months. Metastasectomy was performed in 25/52 (48%) patients and was associated with a significant improvement in OS, 23 vs 51 months ( p < 0.005, HR 0.4). Conclusions: Mucinous CRC has been associated with inferior responses to treatment and worse overall outcomes compared to non-mucinous histologies. Survival in advanced-stage disease in our cohort is higher than what has been reported in the literature. With an effective multi-disciplinary approach and the increasing use of metastasectomy as a treatment option, survival in the advanced disease setting may be comparable to non-mucinous CRC.


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