Adjuvant capecitabine and oxaliplatin for gastric cancer: Results of the phase III CLASSIC trial.

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. LBA4002-LBA4002 ◽  
Author(s):  
Y. Bang ◽  
Y. W. Kim ◽  
H. Yang ◽  
H. C. Chung ◽  
Y. Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Data Monitoring Committee ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Recurrence Rates ◽  
Significance Level ◽  
D2 Gastrectomy ◽  
Recommended Treatment ◽  
Grade 3

LBA4002 Background: Surgical resection is a recommended treatment for operable gastric cancer (GC) in general, despite high recurrence rates (40%–80%). Adjuvant chemotherapy aims to reduce recurrences; however, there is currently no universally accepted adjuvant regimen for GC. Methods: CLASSIC is a randomized, open-label, multicenter, international (South Korea, China, and Taiwan) study of XELOX (capecitabine 1000mg/m2 bid, d1–14, q3w and oxaliplatin 130mg/m2, d1, q3w x 8 cycles) vs observation, following D2 gastrectomy. Eligible patients were chemotherapy- and radiotherapy-naive, with stage II (T2N1, T1N2, T3N0), IIIa (T3N1, T2N2, T4N0), or IIIb (T3N2) GC resected within 6 weeks prior to randomization. The primary endpoint is 3-year disease-free survival (DFS). A sample size of 512 patients per arm was planned to observe the 385 DFS events required to provide 80% power at a 5% significance level for the hypothesized treatment effect (hazard ratio [HR] 0.75). The Independent Data Monitoring Committee recommended full evaluation and reporting of results following a positive pre-planned interim analysis at 266 events. Results: The XELOX and observation arms (ITT populations of 520 and 515 patients, respectively) were well balanced for baseline characteristics. The median duration of follow-up was 34.4 (16–51) months. XELOX-related grade 3/4 adverse events (AEs) occurred in 244/496 patients (49%) of the safety population. Neutropenia was the only AE observed in >10% of patients (21%, n=106/496). Serious XELOX-related grade 3/4 AEs occurred in 34/496 patients (7%). There were 62/496 (13%) and 80/476 (17%) deaths on study in the safety populations of XELOX and observation arms, respectively, mostly due to disease progression. Efficacy results in the ITT population are summarized below. Conclusions: This study demonstrates the superior efficacy of adjuvant XELOX vs observation alone following D2 gastrectomy. Although OS data are still immature, there is a trend towards superiority of XELOX. These data support the use of adjuvant XELOX for GC. [Table: see text]

Adjuvant paclitaxel followed by oral fluoropyrimidines for gastric cancer: Safety data of the factorial phase III SAMIT trial.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 72-72
Author(s):  
Michiya Kobayashi ◽  
Akira Tsuburaya ◽  
Kazuhiro Yoshida ◽  
Shigefumi Yoshino ◽  
Yumi Miyashita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Safety Data ◽  
Data Monitoring Committee ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Number Of Patients ◽  
Grade 3 ◽  
Lavage Cytology ◽  
Disease Free

72 Background: Adjuvant chemotherapy with fluoropyrimidine (FP) with or without platinum for gastric cancer (GC) has become standard almost worldwide; however, there has been no comparison among concurrent, sequential, and monotherapy. Paclitaxel (PTX) is one of key drugs in GC widely used as 2nd-line chemotherapy in Japan. Methods: SAMIT is a randomized, multicenter phase III study of FP (S1 or UFT) vs. PTX followed by FP in patients (pts) with gastric adenocarcinoma. Eligibility includes T3/T4, N0-2, M0 except for positive lavage cytology, chemotherapy- and radiotherapy- naive, being able to start chemotherapy 14 and 56 days after D2 gastrectomy. Pts received either UFT 267 mg/m2/day for 4w, q4w x 6 cycles (arm A); S1 80 mg/m2/day for 2w, q3w x 8 cycles (arm B); PTX 80 mg/m2 Day 1, 8 for the first 3w x 1 cycle, Day 1, 8, 15 q4w x 2 cycles, followed by UFT 267 mg/m2/day for 4w, q4w x 3 cycles (arm C); or PTX as in C, followed by S1 80 mg/m2/day for 2w, q3w x 4 cycles (arm D). The FP cycles was prolonged by 24w after ACTS-GC publication in 2007. Primary endpoint is disease-free survival and total number of patients was calculated to be1480 where 90% power for superiority of C+D group vs. A+B. The Independent Data Monitoring Committee undertook a review of the 1417 pts at the 2nd interim analysis in 2011. Results: Arm A (n=353), arm B (n=359), arm C (n=352), arm D (n=353) were well balanced for baseline factors. The compliance with UFT in arm A and S1 in B was 74% and 76% in the first 12 weeks, and 89% and 90% between week 37 and 48; that in arm C and D was 83% and 80% in the second 12 weeks, and 94% and 84% between week 37 and 48. Numbers of grade 3/4 hematological and non-hematological adverse events (AEs) were 3 and 46, 0 and 64, 5 and 35, and 16 and 67 for arm A, B, C, and D, respectively. Anorexia was the most common AE observed in 5.8%, 6.8%, 1.7%, and 5.1% for arm A, B, C, and D, respectively. There were 363/1323 (27%) deaths and 762/1323 (58%) of pts survived disease free. Conclusions: Adjuvant chemotherapy with sequential PTX and FP for GC was safe and the compliance of the FP part could be better than that of FP monotherapy. The final efficacy results will be formally assessed in 2012.

APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4000-4000 ◽  
Author(s):  
Margaret A. Tempero ◽  
Michele Reni ◽  
Hanno Riess ◽  
Uwe Pelzer ◽  
Eileen Mary O'Reilly ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Disease Recurrence ◽  
Geographic Region ◽  
Phase Iii ◽  
Lymph Node Status ◽  
Open Label ◽  
Significance Level ◽  
Grade 3 ◽  
Ecog Ps

4000 Background: In metastatic pancreatic cancer (PC), nab-P/G demonstrated significantly longer overall survival (OS) vs G. APACT assessed efficacy & safety of nab-P/G vs G in surgically resected PC. Methods: Treatment (tx)-naive patients (pts) with histologically confirmed PC, macroscopic complete resection, ECOG PS 0/1, & CA19-9 < 100 U/mL were eligible. Stratification factors: resection status (R0/R1), lymph node status (LN+/−), & geographic region. Tx was initiated ≤ 12 wks postsurgery. Pts received nab-P 125 mg/m2 + G 1000 mg/m2 or G 1000 mg/m2 on days 1, 8, 15 of six 28-day cycles. Primary endpoint was disease-free survival (DFS) by independent reviewer (IR); IRs received baseline clinical data & scans. Secondary endpoints were OS & safety. ≈438 DFS events were needed for 90% power to detect an HR for disease recurrence or death of 0.73 with nab-P/G vs G at a 2-sided significance level of 0.05. Results: 866 pts were randomized. Median age was 64 y (range, 34 - 86); most pts had ECOG PS 0 (60%), LN+ (72%), & R0 (76%). 69% of pts completed 6 tx cycles ( nab-P/G, 66%; G, 71%). Median follow up for OS was 38.5 mo. Median IR-assessed DFS (439 events) was 19.4 mo ( nab-P/G) vs 18.8 mo (G) (HR, 0.88; 95% CI, 0.729 - 1.063; stratified log-rank P = 0.1824). Investigator-assessed DFS (571 events) was 16.6 mo ( nab-P/G) vs 13.7 mo (G) (HR, 0.82; 95% CI, 0.694 - 0.965; nominal P = 0.0168). Interim OS (427 events) was 40.5 mo ( nab-P/G) vs 36.2 mo (G) (HR, 0.82; 95% CI, 0.680 - 0.996; nominal P = 0.045). Grade ≥ 3 TEAEs were reported in 86% vs 68% of pts with nab-P/G vs G. The most common grade ≥ 3 hematologic & nonhematologic TEAEs with nab-P/G vs G were neutropenia (49% vs 43%) & fatigue (10% vs 3%). TEAEs led to death in 2 pts in each arm. Conclusions: IR DFS with nab-P/G was not significantly longer vs G; median DFS with G was longer than historical data. DFS by investigator (sensitivity analysis) and interim OS were improved with nab-P/G vs G (HR 0.82 for both). Adjuvant nab-P/G may be an option for pts who are ineligible for FOLFIRINOX. Additional OS follow-up may better support nab-P/G as an option in the adjuvant setting. Clinical trial information: NCT01964430.

scholarly journals Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial

2020 ◽  
Vol 38 (16) ◽  
pp. 1774-1784 ◽  
Author(s):  
Junjie Li ◽  
Keda Yu ◽  
Da Pang ◽  
Changqin Wang ◽  
Jun Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Safety Data ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Control Treatment ◽  
Open Label ◽  
Phase Iii Trial ◽  
Grade 3

PURPOSE Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) includes a taxane and an anthracycline. Concomitant capecitabine may be beneficial, but robust data to support this are lacking. The efficacy and safety of the addition of capecitabine into the TNBC adjuvant treatment regimen was evaluated. PATIENTS AND METHODS This randomized, open-label, phase III trial was conducted in China. Eligible female patients with early TNBC after definitive surgery were randomly assigned (1:1) to either capecitabine (3 cycles of capecitabine and docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide) or control treatment (3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide). Randomization was centralized without stratification. The primary end point was disease-free survival (DFS). RESULTS Between June 2012 and December 2013, 636 patients with TNBC were screened, and 585 were randomly assigned to treatment (control, 288; capecitabine, 297). Median follow-up was 67 months. The 5-year DFS rate was higher for capecitabine than for control treatment (86.3% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = .044). Five-year overall survival rates were numerically higher but not significantly improved (capecitabine, 93.3%; control, 90.7%). Overall, 39.1% of patients had capecitabine dose reductions, and 8.4% reported grade ≥ 3 hand-foot syndrome. The most common grade ≥ 3 hematologic toxicities were neutropenia (capecitabine, 136 [45.8%]; control, 118 [41.0%]) and febrile neutropenia (capecitabine, 50 [16.8%]; control, 46 [16.0%]). Safety data were similar to the known capecitabine safety profile and generally comparable between arms. CONCLUSION Capecitabine when added to 3 cycles of docetaxel followed by 3 cycles of a 3-drug anthracycline combination containing capecitabine instead of fluorouracil significantly improved DFS in TNBC without new safety concerns.

A randomized, open-label, phase III trial of NOV-002 in combination with paclitaxel (P) and carboplatin (C) versus paclitaxel and carboplatin alone for the treatment of advanced non-small cell lung cancer (NSCLC).

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA7007-LBA7007 ◽  
Author(s):  
P. Fidias ◽  
T. A. Ciuleanu ◽  
O. Gladkov ◽  
G. M. Manikhas ◽  
I. N. Bondarenko ◽  
...  
Keyword(s):  
Overall Survival ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Stage Iv ◽  
Phase Iii ◽  
Open Label ◽  
Significance Level ◽  
Phase Ii Studies ◽  
Grade 3 ◽  
Positive Results

LBA7007 Background: NOV-002 is a formulation of disodium glutathione disulfide (GSSG). GSSG is a naturally occurring substance that functions as a component of the glutathione (GSH) pathway, vital to the regulation of the intracellular redox state. A key function of the GSH/GSSG redox couple is to dynamically regulate protein functions, including cell signaling pathways, through the reversible formation of mixed disulfides between protein cysteines and GSH (S-glutathionylation). Based on positive results from a randomized, phase I/II study of carboplatin and paclitaxel (CP) with or without NOV-002, as well as positive results from 2 ex-U.S. phase II studies with cisplatin-based chemotherapy, an international phase III randomized trial was launched. Methods: Patients with advanced NSCLC (stages wet IIIB and IV, inclusive of all histological subtypes) were eligible if they had a PS of 0-1 and adequate end-organ function. Patients with CNS metastases were excluded. Eligible patients were randomized to C (AUC 6), P (200 mg/m2), and NOV-002 (Group A) or C and P alone (Group B). NOV-002 was administered as two-60 mg IV boluses on day -1 of cycle 1 and as one IV bolus on day 1 of each cycle, followed by daily 60-mg subcutaneous injections. A total of 725 events were required to detect a difference in overall survival (OS) from 10.0 to 12.5 months with 85% power and a two-sided significance level of 0.05. No interim analysis was performed. Results: From 11/06 until 9/09, 903 patients were randomized, with target enrollment reached in March 2008. Patient characteristics for Groups A and B were as follows: stage IV (91.5/90.8%), PS 1 (76.6/72.6%), male (69.9/72.4%), never smoker (22.3/19.1%) median age (59.6/59.5), and histology (adenocarcinoma [40.0/36.8%] squamous [41.2/40.8%]). The median overall survival for Groups A and B was 10.2/10.8 months (p = 0.375), median progression-free survival was 5.3/5.6 months, objective response rate was 26.6/26.0% and 54/53% of patients completed at least six cycles of chemotherapy. Major toxicities for Groups A and B included grade 3/4 neutropenia (29.7/26.3%), febrile neutropenia (2.2/1.8%), grade 3/4 thrombocytopenia (3.8/2.9%), and grade 3/4 neuropathy (2.9/2.4%). Adverse events resulting in death in Groups A and B were reported in 5.6 and 3.1%, respectively. Conclusions: The addition of NOV-002 to CP does not improve overall survival in patients with advanced NSCLC. NOV002 does not appear to add to the overall toxicity of chemotherapy. [Table: see text]

SAMIT: A phase III randomized clinical trial of adjuvant paclitaxel followed by oral fluorinated pyrimidines for locally advanced gastric cancer.

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. LBA4002-LBA4002 ◽  
Author(s):  
Kazuhiro Yoshida ◽  
Akira Tsuburaya ◽  
Michiya Kobayashi ◽  
Shigefumi Yoshino ◽  
Masazumi Takahashi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Significance Level ◽  
D2 Lymph Node Dissection ◽  
Locally Advanced Gastric Cancer ◽  
Number Of Patients ◽  
Grade 3 ◽  
Fluorinated Pyrimidines

LBA4002 Background: Adjuvant chemotherapy with tegafur/uracil (UFT) used to be a tentative Japanese standard treatment and has been replaced by S-1 according to the result of the ACTS-GC trial, although there has been no direct comparison. Paclitaxel (PTX) has been widely used as one of the key drugs for unresectable GC. A randomized phase III trial with a two-by-two factorial design was planned to assess the survival benefit of sequential use of PTX and oral fluorinated pyrimidines (FPs) in comparison with FPs alone, and to compare UFT and S-1. Methods: Patients with serosa-invading GC who underwent R0/1 resection with extended (D2) lymph node dissection were randomized to receive either UFT 267mg/m2 daily (arm A), S-1 80mg/m2 daily for 2 weeks every 3 weeks (B), weekly PTX 80 mg/m2 followed by UFT (C), or PTX followed by S-1 (D) for 24 weeks. The primary endpoint was disease-free survival (DFS). 708 patients per groups were necessary to detect a hazard ratio of 0.8 with 90% power for superiority of the sequential arms, C+D, vs. A+B (two-sided 5.0% significance level). The number of patients was set to 370 per arm (total 1480) with an 88% power for noninferiority (1.33 as the margin) of UFT vs. S-1. Results: Between August 2004 and October 2007, 1,495 patients from 232 centers were randomized with the full analysis set of 1,433. Demographics were well balanced among arm A (n=359), B (n=364), C (n=355), and D (n=355); mean age was 64, 86% were PS 0, 68% of tumors were 8 cm or greater and 85% were clinically node positive. Grade 3-4 neutropenia or anorexia occurred in 11% or 6%, 13% or 7%, 13% or 2%, and 23% or 5% for arm A, B, C, and D, respectively. Other % grade 3-4 toxicities were less than 5%. Median follow-up was 1,875 days and 728 events occurred. Difference in DFS between C+D and A+B were not statistically significant (HR=0.92, 95%CI 0.80-1.07, p= 0.273). HR of A+C vs. B+D was 1.23 (95%CI 1.07-1.43) and hence the null hypothesis was not rejected. Conclusions: There was a trend for better DFS for sequential use of PTX followed by FPs. Comparison between the FPs demonstrated that UFT was inferior to S-1. Sequential PTX/S-1 is safe and effective for locally advanced GC in an adjuvant setting. Clinical trial information: C000000082.

Phase II feasibility study of adjuvant S-1 plus docetaxel for stage III gastric cancer patients after curative D2 gastrectomy (OGSG 0604)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15567-e15567
Author(s):  
K. Fujitani ◽  
S. Tamura ◽  
Y. Kimura ◽  
T. Tsuji ◽  
J. Matsuyama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
R0 Resection ◽  
D2 Gastrectomy ◽  
Grade 3

e15567 Background: Although an adjuvant chemotherapy with S-1 has become the standard treatment for stage II-III gastric cancer (GC) patients (pts) after curative D2 gastrectomy in Japan, the survival benefit for stage III pts obtained by S-1 is considered to be modest. S-1 plus docetaxel has shown a good response rate of 56% with prolonged median overall survival (OS) of 14.3 months in pts with advanced GC. This phase II study evaluated the feasibility and safety of adjuvant S-1 plus docetaxel for stage III GC pts after R0 resection. Methods: Patients with curatively resected pathological stage III GC receiving D2 dissection, age 20–80 years, performance status < 1, no prior adjuvant treatment, adequate organ function, and informed consent were given S-1 (80 mg/m2/day) orally for consecutive 2 weeks plus docetaxel (40 mg/m2) intravenously on day 1, repeated every 3 weeks. The treatment was started within 45 days after gastrectomy, and repeated for 4 cycles, followed by S-1 monotherapy until 1 year after surgery. Study endpoints included feasibility of the 4 cycles of S-1 plus docetaxel as primary, and safety, progression free survival (PFS), and OS as secondary. Sample size was set to be 50, which was determined to reject the feasibility of 50% under the expectation of 75% with power of 90% and two-sided α of 5%. Results: Fifty-three pts, 42 males and 11 females with a median age of 65 years, were enrolled between 5/2007 and 8/2008. Pathological stages included IIIA in 36 pts and IIIB in 17 pts. Planned 4 cycles of treatment were delivered to 41 out of 53 pts, with the feasibility of 77.4% (95% CI 63.8–87.7%, P<0.001). Reasons for discontinuation were recurrent cancer in 1 pt, adverse events in 10, and miscellaneous in 1, respectively. Grade 4 neutropenia was observed in 28% of pts with grade 3 febrile neutropenia in 9%. Non-hematological toxicities of grade 3 or more involved fatigue in 6%, anorexia in 9%, and nausea in 6%. No treatment-related deaths occurred. Conclusions: Adjuvant S-1 plus docetaxel was well-tolerated and showed good compliance. Although follow-up is ongoing on survival, this regimen could be a candidate of future phase III trial seeking for the optimal adjuvant chemotherapy for stage III GC pts after curative D2 gastrectomy. No significant financial relationships to disclose.

ARTIST 2: Interim results of a phase III trial involving adjuvant chemotherapy and/or chemoradiotherapy after D2-gastrectomy in stage II/III gastric cancer (GC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4001-4001 ◽  
Author(s):  
Se Hoon Park ◽  
Dae Young Zang ◽  
Boram Han ◽  
Jun Ho Ji ◽  
Tae Gyu Kim ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Subtotal Gastrectomy ◽  
Data Monitoring Committee ◽  
Disease Free Survival ◽  
Patient Characteristics ◽  
Stage Ii ◽  
Phase Iii ◽  
Significance Level ◽  
Node Positive ◽  
Resected Stage

4001 Background: Adjuvant chemotherapy and/or chemoradiotherapy have been the standard of care in GC for years, supported by randomized trials. We compared the efficacy of different chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II/III, node-positive GC. Methods: From Feb 2013 through Nov 2018, we randomly assigned, in a 1:1:1 ratio, patients with pathologically-staged II or III, node-positive, D2-resected GC, to receive adjuvant S-1 (40-60 mg twice daily 4-weeks-on/2-weeks-off) for one year, S-1 (2-weeks-on/1-week-off) plus oxaliplatin 130 mg/m2 (SOX) for six months, or SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to the type of surgery (total or subtotal gastrectomy), stage (II or III), and Lauren histologic classification (diffuse or intestinal). The primary endpoint was disease-free survival (DFS). A total of 900 patients had to be enrolled to demonstrate superiority of SOX or SOXRT to S-1 (hazard ratio [HR] 0.667), with 90% power at a two-sided significance level of 5%. Results: A total of 538 patients were included for this interim efficacy analysis. Median age was 58 years, men constituted 65%, and stage II and III were 31% and 69%, respectively. Baseline tumor and patient characteristics were balanced between treatment arms. Adverse events were as anticipated in each arm, generally well-tolerated and manageable. DFS in the control arm (S-1) were significantly shorter than in SOX and SOXRT arms (stratified HR for recurrence): S-1 vs. SOX, 0.617 (P = 0.016) and S-1 vs. SOXRT, 0.686 (P = 0.057). The DFS at 3-years was found to be 65%, 78% and 73% in S-1, SOX and SOXRT arms, respectively. No difference in DFS between SOX and SOXRT was found (HR 0.910, P = 0.667). Based on the results after the observation of 145 recurrence events at the cutoff date of Dec 27, 2018, the independent data monitoring committee considered the results sufficient to meet the endpoint of the trial and recommended early stopping of the trial. Conclusions: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared to S-1 monotherapy. Clinical trial information: NCT0176146.

scholarly journals Adjuvant albumin-bound paclitaxel combined with S-1 vs. oxaliplatin combined with capecitabine after D2 gastrectomy in patients with stage III gastric adenocarcinoma: a phase III multicenter, open-label, randomized controlled clinical trial protocol

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiangdong Cheng ◽  
Dan Wu ◽  
Nong Xu ◽  
Luchuan Chen ◽  
Zhilong Yan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Clinical Study ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Phase Iii ◽  
Stage Iii ◽  
Open Label ◽  
D2 Gastrectomy

Abstract Background Surgery is the only treatment option for operable gastric cancer. The CLASSIC and ACTS-GC studies showed that the 5-year overall survival (OS) of patients with stage III gastric cancer undergoing D2 gastrectomy is still very low. Whether adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) combined chemotherapy is more effective than the XELOX standard adjuvant chemotherapy in patients with stage III gastric cancer has not been confirmed. Methods This is a multicenter, open-label, phase III clinical study. In this trial, 616 patients with locally advanced stage III gastric cancer that underwent curative D2 radical surgery and achieved R0 are planned to be included. Patients will be randomized 1:1 to nab-paclitaxel combined with S-1 (AS) vs. oxaliplatin combined with capecitabine (XELOX). XELOX group: Patients assigned to the XELOX group received eight 3-week cycles of oral capecitabine (1000 mg/m2) twice daily on days 1–14 of each cycle plus intravenous oxaliplatin 130 mg/m2 on day 1 of each cycle. AS group: AS group received eight 3-week cycles of oral S-1 (80–120 mg) (< 1.25 m2, 40 mg; 1.25 to < 1.5 m2, 50 mg; and > 1.5 m2, 60 mg) twice daily on days 1–14 plus intravenous nab-paclitaxel 120 mg/m2 on days 1 and 8 of each cycle. The primary endpoint was the 3-year disease-free survival (3-year-DFS) defined as the time from randomisation to the time of recurrence of the original gastric cancer, development of a new gastric cancer, or death from any cause. The secondary endpoints were the overall survival, (defined as the time from the date of randomisation to date of death from any cause) and safety (any adverse event). Discussion Compared with previous studies, this study includes nab-paclitaxel based on S-1 adjuvant chemotherapy, which is expected to achieve better efficacy and lower toxicity than the standard treatment. This study is the first clinical study to evaluate the safety and efficacy of nab-paclitaxel combined with S-1 in patients with stage III gastric cancer after D2 radical resection. Trial registration This clinical trial has been registered with ClinicalTrials.gov, registration number: NCT04135781, on October 20th, 2019.

Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 205-205
Author(s):  
Daisuke Takahari ◽  
Manabu Ohashi ◽  
Atsuo Takashima ◽  
Takuro Mizukami ◽  
Naoki Ishizuka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Complete Response ◽  
Free Survival ◽  
D2 Gastrectomy ◽  
Locally Advanced Gastric Cancer ◽  
Grade 3

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m2, intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in < 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.

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