scholarly journals Updated Analysis of SWOG-Directed Intergroup Study 0116: A Phase III Trial of Adjuvant Radiochemotherapy Versus Observation After Curative Gastric Cancer Resection

2012 ◽  
Vol 30 (19) ◽  
pp. 2327-2333 ◽  
Author(s):  
Stephen R. Smalley ◽  
Jacqueline K. Benedetti ◽  
Daniel G. Haller ◽  
Scott A. Hundahl ◽  
Norman C. Estes ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Substantial Reduction ◽  
Phase Iii ◽  
R0 Resection ◽  
Second Malignancies ◽  
Adjuvant Radiochemotherapy ◽  
Phase Iii Trial ◽  
Failure Patterns ◽  
Postoperative Radiochemotherapy

Purpose Surgical resection of gastric cancer has produced suboptimal survival despite multiple randomized trials that used postoperative chemotherapy or more aggressive surgical procedures. We performed a randomized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure (LRF) following surgery. We originally reported results with 4-year median follow-up. This update, with a more than 10-year median follow-up, presents data on failure patterns and second malignancies and explores selected subset analyses. Patients and Methods In all, 559 patients with primaries ≥ T3 and/or node-positive gastric cancer were randomly assigned to observation versus radiochemotherapy after R0 resection. Fluorouracil and leucovorin were administered before, during, and after radiotherapy. Radiotherapy was given to all LRF sites to a dose of 45 Gy. Results Overall survival (OS) and relapse-free survival (RFS) data demonstrate continued strong benefit from postoperative radiochemotherapy. The hazard ratio (HR) for OS is 1.32 (95% CI, 1.10 to 1.60; P = .0046). The HR for RFS is 1.51 (95% CI, 1.25 to 1.83; P < .001). Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse. Second malignancies were observed in 21 patients with radiotherapy versus eight with observation (P = .21). Subset analyses show robust treatment benefit in most subsets, with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect. Conclusion Intergroup 0116 (INT-0116) demonstrates strong persistent benefit from adjuvant radiochemotherapy. Toxicities, including second malignancies, appear acceptable, given the magnitude of RFS and OS improvement. LRF reduction may account for the majority of overall relapse reduction. Adjuvant radiochemotherapy remains a rational standard therapy for curatively resected gastric cancer with primaries T3 or greater and/or positive nodes.

Update of AMC 0201 study: A randomized phase III trial comparing mitomycin-C plus short-term doxifluridine (Mf) versus mitomycin-C plus long-term doxifluridine plus cisplatin (MFP) after curative resection of advanced gastric cancer (NCT00296335).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 76-76 ◽  
Author(s):  
Baek-Yeol Ryoo ◽  
Yoon-Koo Kang ◽  
Young Joo Min ◽  
Dae Young Zang ◽  
Gyu Yeol Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Mitomycin C ◽  
Phase Iii ◽  
R0 Resection ◽  
Long Term Follow Up ◽  
Asco Meeting

76 Background: Despite a continuing debate on the role of adjuvant chemotherapy, several studies have suggested that mitomycin-C (M) plus fluoropyrimidine (f) could improve the outcome of curatively resected advanced gastric cancer (AGC) patients (pts). To improve further the adjuvant Mf chemotherapy, we have prolonged the administration of oral fluoropyrimidine (F) and added cisplatin (P) to Mf (MFP) and performed a phase III randomized trial to determine whether this strategy could improve the 3-year relapse free survival (3yRFS) in curatively resected AGC pts (HR=0.63, α=0.05, β=0.1). Three year follow-up results were reported in 2008 ASCO meeting. Here we report long-term follow-up results for confirmation. Methods: Three to 6 wks after R0 resection, the pts who had postoperative stage II-IV were randomized to receive either Mf or MFP adjuvant chemotherapy. For Mf group, 20 mg/m2 of M was iv injected and 4 wks later, 460-600 mg/m2/day of doxifluridine was administered orally for 3 months. For MFP group, the administration of doxifluridine was extended for a total of 12 months and 6 shots of monthly 60 mg/m2 of cisplatin were added to Mf. Results: Between Feb 2002 and Aug 2006, a total of 871 pts were randomized (435 in Mf, 436 in MFP). Sixteen pts were excluded because of ineligibility (11 in Mf, 5 in MFP). Postoperative stages were II in 51.0%, IIIA in 31.1%, IIIB in 9.4%, and IV in 8.5% of pts. With a median follow up of 6.6 yrs in April 2011, a total of 353 events (relapse or death) have been observed. There was no difference in RFS between the two groups (HR, 1.10; 95% C.I. 0.89 – 1.35; p=0.3918; 5yRFS 61.1% in Mf and 57.9% in MFP). Difference in overall survival (OS) was also insignificant (HR, 1.11; 95% C.I. 0.89 – 1.39; p=0.3349; 5yOS 66.5% in Mf and 65.0% in MFP). Conclusions: Long-term follow-up results of AMC 0201 trial confirmed prolongation of doxifluridine administration and addition of cisplatin to adjuvant chemotherapy with mitomycin-C plus 3 months of doxifluridine did not improve the treatment outcome in curatively resected AGC pts.

The triplet combination of irinotecan, oxaliplatin and 5FU/LV (FOLFOXIRI) vs the doublet of irinotecan and 5FU/LV (FOLFIRI) as first-line treatment of metastatic colorectal cancer (MCRC): Results of a randomized phase III trial by the Gruppo Oncologico Nord Ovest (G.O.N.O.)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3513-3513 ◽  
Author(s):  
A. Falcone ◽  
G. Masi ◽  
I. Brunetti ◽  
G. Benedetti ◽  
O. Bertetto ◽  
...  
Keyword(s):  
Phase Iii ◽  
R0 Resection ◽  
Peripheral Neurotoxicity ◽  
Phase Iii Trial ◽  
Secondary Resection ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Increased Activity

3513 Background: We demonstrated interesting activity and manageable toxicities for the FOLFOXIRI regimen in phase I-II studies. Methods: The G.O.N.O. conduced a phase III study comparing FOLFIRI (CPT11 180 mg/sqm d1, l-LV 100 mg/sqm d1+d2, 5FU 400 mg/sqm bolus d1+d2, 5FU 600 mg/sqm 22-h inf. on d1+d2, arm A), to FOLFOXIRI (CPT11 165 mg/sqm d1, LOHP 85 mg/sqm d1, l-LV 200 mg/sqm d1, 5FU 3200 mg/sqm 48-h inf. starting on d1, arm B). Both treatments were repeated every 2 weeks and at progression to FOLFIRI a FOLFOX combination was recommended. Selection criteria included measurable and not resectable MCRC, age 18–75 years, no prior chemotherapy for advanced disease. Primary endpoint was response rate (RR) and planned accrual was 240 pts. Secondary endpoints were PFS, OS, post-CT R0 surgical resections, safety and QoL. Results: A total of 244 pts were randomized. Main toxicities were (arm A/arm B): grade 3–4 diarrhea 12%/20%, grade 3–4 vomiting 2%/7%, grade 3–4 stomatitis 3%/5%, grade 2–3 peripheral neurotoxicity 0%/20%, grade 4 neutropenia 11%/17%, febrile neutropenia 3%/5%. Two pts in each arm died within 60 days, but no toxic deaths occurred. Responses, assessed by investigators, were (arm A/arm B): complete 6%/8%, partial 35%/58%, stable 33%/21%, progression 24%/11%, for an overall RR of 41% vs 66%, p=0.0002. RR confirmed by an external panel was 34%/60%, p<0.0001. This increased activity allowed a radical secondary resection of mts in a greater percentage of patients in the FOLFOXIRI arm (6% vs 14%, p=0.05, among all 244 pts and 12% vs 36%, p=0.02, among 81 patients with liver mts only). At a median follow-up of 15.2 months 112 vs 104 pts have progressed and 81 vs 65 have died with a significant improvement in progression-free and overall survival in favor of the triplet (median PFS 6.9 vs 9.8 mos, HR: 0.63, p=0.0006; median S 16.7 vs 22.6, HR:0.70, p=0.032). Conclusions: The FOLFOXIRI regimen is feasible with manageable toxicities and significantly increases RR, R0 resection of mts, PFS and overall S compared to FOLFIRI. (Partially supported by Fondazione ARCO). [Table: see text]

Follow up of a multicenter phase II study of sequential paclitaxel and S-1 (TXL/S1) as postoperative adjuvant chemotherapy for gastric cancer (GC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15084-15084
Author(s):  
A. Tsuburaya ◽  
N. Murata ◽  
M. Kimura ◽  
Y. Ueda ◽  
M. Takahashi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Phase Iii ◽  
R0 Resection ◽  
Peritoneal Cytology ◽  
Primary Analysis ◽  
Eligibility Criteria ◽  
Phase Ii Studies

15084 Background: Of patients who undergo R0 resection for GC with serosal invasion (T3–4), more than half recur mainly in the peritoneum, while TXL and S1 exhibited efficacy for diffuse type and peritoneal metastases in the phase II studies. Primary analysis of the sequential chemotherapy with TXL/S1 had shown its safety and tolerability, its survival benefit is being tested in a large phase III study (the SAMIT trial) with oral fluoropyrimidines as controls. The analysis for survival of this preceding phase II study is performed. Methods: Eligibility criteria included histologically proven GC; sT3–4; sN0–2; M0 (except peritoneal cytology: CY); post D2–3 gastrectomy and R0–1; ECOG PS 0–1; and 20–80 years old. On postoperative day 14 to 56, patients received 3 courses of weekly TXL (80mg/m2 on day 1, 8 for the 1st course and on day 1, 8, 15 for the 2nd and 3rd courses, repeated every 3 or 4 weeks) followed by 4 courses of S1 (80mg/m2 daily for 2 weeks, repeated every 3 weeks). The primary endpoints were % of patients who completed all 7 courses (compliance) to see whether the lower 95% confidence limit of compliance was greater than 69% and incidence of severe toxicities and the secondary endpoints were 3-year survival and toxicities. Results: 50 patients were accrued from May 2003 to March 2004. The median age was 63 (range 34–74); male/female: 34/16; pT2/T3/T4: 1/44/5; CY0/CY1: 4/46; f-stage2/3a/3b/4: 12/15/16/7. The overall compliance was 84%. Median follow up time was 1063 days for survivors (694–1332) and 1030 days for all. Three-year DFS were 64.6% for all, 66.1% for CY0 and 50.0% for CY1. Conclusions: Sequential TXL/S1 may serve as an active adjuvant for gastric cancer patients especially who are at high risk for peritoneal spread. No significant financial relationships to disclose.

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