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Postoperative chemoradiotherapy in gastric cancer -- a Phase I/II dose-finding study of radiotherapy with dose escalation of cisplatin and capecitabine chemotherapy.

ABSTRACT: We hypothesised that gastric cancer outcome could be improved with more effective and intensified postoperative chemoradiotherapy. This phase I/II study was performed to determine the maximal tolerated dose (MTD) and toxicity profile of postoperative radiotherapy with concurrent daily cisplatin and capecitabine. Patients were treated with capecitabine 1000 mg m(-2) twice a day (b.i.d.) for 2 weeks. Subsequently, patients received capecitabine (250-650 mg m(-2) orally b.i.d., 5 days week(-1)) and cisplatin (3-6 mg m(-2) i.v., 5 days week(-1)) according to an alternating dose-escalation schedule. Radiotherapy was given to a total dose of 45 Gy in 25 fractions. Thirty-one patients completed treatment. During chemoradiotherapy, eight patients developed nine items of grade III and one episode of grade IV (mainly haematological) toxicity. The MTD was determined to be cisplatin 5 mg m(-2) i.v. and capecitabine 650 mg m(-2) b.i.d. orally. This phase I/II study demonstrated that chemoradiotherapy with daily cisplatin and capecitabine is feasible in postoperative gastric cancer at the defined dose level and is currently being tested in a phase III multicenter study.

SUBMITTER: Jansen EP

PROVIDER: S-EPMC2360378 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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Postoperative chemoradiotherapy in gastric cancer -- a Phase I/II dose-finding study of radiotherapy with dose escalation of cisplatin and capecitabine chemotherapy.

Jansen E P M EP Boot H H Dubbelman R R Bartelink H H Cats A A Verheij M M

British journal of cancer 20070901 6

We hypothesised that gastric cancer outcome could be improved with more effective and intensified postoperative chemoradiotherapy. This phase I/II study was performed to determine the maximal tolerated dose (MTD) and toxicity profile of postoperative radiotherapy with concurrent daily cisplatin and capecitabine. Patients were treated with capecitabine 1000 mg m(-2) twice a day (b.i.d.) for 2 weeks. Subsequently, patients received capecitabine (250-650 mg m(-2) orally b.i.d., 5 days week(-1)) and ...[more]

PMID: 17848909

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Project description:BackgroundWorldwide, almost one million new cases of stomach cancer were diagnosed in 2012, making it the fifth most common cancer, and the third leading cause of cancer deaths. The current tumor node metastasis (TNM) staging system represents a consensus between the East and the West, and will serve as a strong foundation upon which to build future evidence. In this review article, we first discuss the definition and optimal surgery for locally advanced gastric cancer, followed by the general principles when considering a pre vs. postoperative radiotherapy (RT) strategy. We then provide a synthesis of the existing randomized trial evidence in an attempt clarify the role of pre and postoperative RT in the management of locally advanced gastric cancer.MethodsA Medline search 1966-Jun 2014 was undertaken. Randomized trials including patients with locally advanced gastric cancer (using established definitions), comparing RT [with or without chemotherapy (CT)], with surgery alone or other treatment modalities were included. Systematic reviews and evidence based practice guidelines that include this body of primary studies were preferentially discussed. Medline, Cochrane Library, Clinicaltrial.gov, Guidelines Clearinghouse were searched.ResultsSixteen randomized trials, three systematic reviews and one practice guideline were included as the evidence base. In this group of studies, two reports compared postoperative chemoradiotherapy (CRT) with surgery alone. Driven predominantly by INT0116, they established the role of postoperative CRT to provide a survival benefit in a patient group that underwent surgery with predominantly D0-1 dissections. Preoperative RT (four studies) showed promise for survival benefit but the risks of bias in these trials were high. Postoperative CRT compared with CT alone (eight trials) showed no survival benefit with the addition of radiation although some evidence of activity can be observed with improved local regional control.Conclusions and future directionsTechnical expertise to enable the delivery of high quality RT to complex target volumes as is required in gastric cancer, and surgical standards to ensure the delivery of high quality surgery, have matured in recent years. Six trials with large sample sizes are currently ongoing to better define the role of preoperative CRT (two studies) and postoperative CRT (four studies), when used in conjunction with high quality surgery and RT, and contemporary CT regimens. The moderate likelihood of locoregional recurrences and the favorable therapeutic ratio with using RT preoperatively in other settings, provide optimism that preoperative CRT would have a pivotal role to play in locally advanced gastric cancer. Active accrual into ongoing trials is strongly encouraged.

Project description:ImportanceSeveral studies have explored the efficacy and toxic effects of concurrent 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) with or without oxaliplatin in the neoadjuvant setting. Addition of oxaliplatin to 5-FU or capecitabine elicited similar outcomes but with significantly increased toxic effects; however, there is a need for randomized clinical trials comparing 2 CRT regimens for patients receiving CRT in the adjuvant setting.ObjectiveTo explore the efficacy and toxic effects of oxaliplatin combined with postoperative concurrent capecitabine and radiotherapy (RT) for pathological stage II and III rectal cancer.Design, setting, and participantsThis multicenter randomized clinical trial enrolled patients from 7 centers in China between April 1, 2008, and December 30, 2015. Patients with pathologically confirmed stage II and III rectal cancer were randomized (1:1) to receive concurrent CRT with capecitabine or capecitabine plus oxaliplatin. Analysis was conducted from December 31, 2019, to March 15, 2020.InterventionsRT comprised 45 to 50 Gy in 25 fractions of 1.8 to 2.0 Gy over 5 weeks. In the capecitabine with RT group, concurrent chemotherapy included 2 cycles of capecitabine (1600 mg/m2) on days 1 to 14 and 22 to 35. The capecitabine and oxaliplatin with RT group received identical postoperative RT to that in the capecitabine with RT group combined with capecitabine (1300 mg/m2) on days 1 to 14 and 22 to 35 and a 2-hour infusion of oxaliplatin (60 mg/m2) on weeks 1, 2, 4, and 5. Patients in both groups received adjuvant chemotherapy (capecitabine or fluorouracil and oxaliplatin) after CRT.Main outcomes and measuresThe primary end point was 3-year disease-free survival (DFS).ResultsA total of 589 patients (median [IQR] age, 55 [47-52] years; 375 [63.7%] men and 214 [36.3%] women) were enrolled, including 294 patients randomized to the capecitabine with RT group and 295 patients randomized to the capecitabine and oxaliplatin with RT group. Median (IQR) follow-up was 68 (45-96) months. Most patients had stage III disease (574 patients [75.9%]). Three-year DFS was 76.3% for the capecitabine with RT group and 74.1% for the capecitabine and oxaliplatin with RT group, and 5-year DFS was 72.0% for the capecitabine with RT group and 71.1% for the capecitabine and oxaliplatin with RT group (hazard ratio [HR], 1.07; 95% CI, 0.79-1.44; P = .68). There was no significant difference between groups in overall survival (HR, 0.93; 95% CI, 0.64-1.34; P = .70) or local recurrence (HR, 0.61; 95% CI, 0.31-1.22; P = .16). More grade 3 and 4 acute toxic effects were observed in the capecitabine and oxaliplatin with RT group than in the capecitabine with RT group (114 patients [38.6%] vs 84 patients [28.6%]; P = .01).Conclusions and relevanceThis randomized clinical trial found that addition of oxaliplatin to capecitabine-based postoperative CRT did not improve the efficacy of treatment but increased the risk of severe acute toxic effects. This finding highlights the basic role of postoperative capecitabine with RT for patients with locally advanced rectal cancer.Trial registrationClinicalTrials.gov Identifier: NCT00714077.

Dataset Information

Postoperative chemoradiotherapy in gastric cancer -- a Phase I/II dose-finding study of radiotherapy with dose escalation of cisplatin and capecitabine chemotherapy.

Publications

Postoperative chemoradiotherapy in gastric cancer -- a Phase I/II dose-finding study of radiotherapy with dose escalation of cisplatin and capecitabine chemotherapy.

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