Dataset Information

A Randomized Phase III Study of Patients With Advanced Gastric Adenocarcinoma Without Progression After Six Cycles of XELOX (Capecitabine Plus Oxaliplatin) Followed by Capecitabine Maintenance or Clinical Observation.

ABSTRACT:

Purpose

Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy.

Materials and methods

Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level.

Results

Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250-0.890; P=0.020).

Conclusions

After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.

Trial registration

ClinicalTrials.gov Identifier: NCT02289547.

SUBMITTER: Lee GJ

PROVIDER: S-EPMC10154142 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

A Randomized Phase III Study of Patients With Advanced Gastric Adenocarcinoma Without Progression After Six Cycles of XELOX (Capecitabine Plus Oxaliplatin) Followed by Capecitabine Maintenance or Clinical Observation.

Lee Guk Jin GJ Kim Hyunho H Cho Sung Shim SS Park Hyung Soon HS An Ho Jung HJ Woo In Sook IS Byun Jae Ho JH Hong Ji Hyung JH Ko Yoon Ho YH Sun Der Sheng S Won Hye Sung HS Jin Jong Youl JY Park Ji Chan JC Kim In-Ho IH Roh Sang Young SY Shim Byoung Yong BY

Journal of gastric cancer 20230401 2

<h4>Purpose</h4>Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC ...[more]

PMID: 37129155

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Project description:BackgroundEpidermal growth factor receptor (EGFR) is overexpressed in pancreatic cancer. EGFR expression plays a potentially important role in modulation of tumor sensitivity to either chemotherapy or radiotherapy. Erlotinib is a receptor tyrosine kinase inhibitor with specificity for EGFR/HER1. A phase II trial was conducted to explore the efficacy of a regimen utilizing erlotinib and proton therapy.MethodsPatients with unresectable or borderline resectable non-metastatic adenocarcinoma of the pancreas were included. Patients received 8-week systemic treatment with gemcitabine 1,000 mg/m2 and erlotinib 100 mg (GE). If there was no evidence of metastatic disease after GE, then patients preceded with proton therapy to 50.4 Gy in 28 fractions with concurrent capecitabine 825 mg/m2 (CPT). This was followed with oxaliplatin 130 mg/m2 and capecitabine 1,000 mg/m2 (CapOx) for 4 cycles. The primary study objective was 1-year overall survival (OS). The benchmark was 43% 1-year survival as demonstrated in RTOG/NRG 98-12. The Kaplan-Meier method was used to estimate the one-year OS and the median OS and progression-free survival (PFS).ResultsThe study enrolled 9 patients ages 47-81 years old (median 62) between January 2013 and March 2016, when the trial was closed due to low patient accrual. The 1-year OS rate was 55.6% (95% CI: 31% to 99%). The median OS was 14.1 months (95% CI: 11.4-NE) and the median PFS was 10.8 months (95% CI: 7.44-NE). A majority of patients completed CPT and GE, but only 33.3% completed the four cycles of CapOx. A third of patients experienced grade 3 toxicities, which were all hepatic along with one patient who also had grade 3 diarrhea. There were no grade 4 or 5 toxicities. Four patients were enrolled with borderline resectable disease, three of which were eligible for pancreaticoduodenectomy after GE and CPT treatment. One of two patients who underwent resection had a negative margin.ConclusionsThis regimen for locally advanced pancreatic cancer (LAPC) exceeded the pre-specified benchmark and was safe and well tolerated. Additional investigations utilizing more current systemic treatment regimens with proton therapy are warranted.Trial registrationClinicalTrials.gov identifier (NCTNCT01683422).

Project description:Lessons learnedThe NEO-CLASSIC study provided valuable insight for the clinical efficacy and tolerability profiles of perioperative chemotherapy with oxaliplatin and capecitabine, plus gastrectomy, in patients with localized resectable gastric cancer.The study was designed to explore the potential survival benefits of an eight-cycle, perioperative oxaliplatin and capecitabine (XELOX) schedule in the above-mentioned setting and to explore the feasibility of prolonging the cycles of preoperative chemotherapy. The projected endpoint was not met.BackgroundThis multicenter, open-label study (NEO-CLASSIC) evaluated the efficacy and safety of oxaliplatin and capecitabine (XELOX), plus D2 gastrectomy, in localized resectable gastric cancer.MethodsPatients aged 18-75 years with histologically-confirmed gastric adenocarcinoma (stage T2-4a/N+M0) were given eight cycles of XELOX (four preoperatively, four postoperatively). Each 3-week cycle comprised capecitabine 1,000 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1. Curative D2 gastrectomy was scheduled 2-4 weeks after the last preoperative cycle. The primary objective of the study was to determine the objective response rate (ORR) of XELOX in the preoperative setting. Sample size was calculated by assuming that a minimum of 47 cases would be required to increase the ORR by 15% (from 40% to 55%). With an estimated 10% dropout rate, 55 patients would have to be recruited.ResultsFifty-five patients were enrolled, and one was excluded because of screening failure. R0 resections were achieved in 45 of 54 intent-to-treat patients (83.3%), and four patients received R1 resections (Fig. 1). There were no complete responses, 27 (50.0%) partial responses, 22 cases (40.7%) of stable disease, and 4 (7.4%) of progressive disease. The objective response rate was 50.0%. Median follow-up was 52.97 months; 30 patients (55.6%) had disease progression (Table 1), and median progression-free survival was 20.10 (95% confidence interval: 4.31-35.89) months; median overall survival was 30.77 months (95% confidence interval was not yet available) (Fig. 2). Fifty-four patients completed 209 cycles of preoperative chemotherapy; 42 patients received 133 cycles of postoperative chemotherapy (Table 3). The rate of grade 3-4 adverse events was 8.5% (29/342 cycles); the most frequent events were neutropenia (9/342 cycles) and leukopenia (4/342 cycles).ConclusionThese findings suggest that combination therapy with capecitabine and oxaliplatin as perioperative chemotherapy, followed by D2 gastrectomy, is effective and safe in late-stage, locally advanced gastric cancer. Although enrollment exceeded the 47 patients required to identify an increase in the ORR by 15% (from 40% to 55%), results did not meet the primary endpoint.

Dataset Information

A Randomized Phase III Study of Patients With Advanced Gastric Adenocarcinoma Without Progression After Six Cycles of XELOX (Capecitabine Plus Oxaliplatin) Followed by Capecitabine Maintenance or Clinical Observation.

Purpose

Materials and methods

Results

Conclusions

Trial registration

Publications

A Randomized Phase III Study of Patients With Advanced Gastric Adenocarcinoma Without Progression After Six Cycles of XELOX (Capecitabine Plus Oxaliplatin) Followed by Capecitabine Maintenance or Clinical Observation.

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