Phase II Trial of Preoperative Chemoradiation in Patients With Localized Gastric Adenocarcinoma (RTOG 9904): Quality of Combined Modality Therapy and Pathologic Response

Duke University, Durham, North Carolina, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 09/2006; 24(24):3953-8. DOI: 10.1200/JCO.2006.06.4840
Source: PubMed


Preoperative therapy for localized gastric cancer has considerable appeal. We hypothesized that, in a cooperative group setting, preoperative chemoradiotherapy would induce a 20% pathologic complete response (pathCR) rate. Combined-modality therapy quality, survival, and safety were secondary end points.
Patients with localized gastric adenocarcinoma were eligible. A negative laparoscopic evaluation was required. Patients received two cycles of induction fluorouracil, leucovorin, and cisplatin followed by concurrent radiation and chemotherapy (infusional fluorouracil and weekly paclitaxel). Resection was attempted 5 to 6 weeks after chemoradiotherapy was completed. Quality of therapy was assessed with other end points.
Twenty institutions participated. Forty-nine patients were entered and 43 were assessable (12% stage IB; 37% stage II; and 52% stage III). The pathCR and R0 resection rates were 26% and 77%, respectively. At 1 year, more patients with pathCR (82%) are living than those with less than pathCR (69%). Grade 4 toxicity occurred in 21% of patients. Chemotherapy, radiotherapy, and surgery per protocol (including acceptable variations) occurred in 98%, 44%, and 63% of patients, respectively. A D2 dissection was performed in 50% of patients. Of 18 major radiotherapy variations, 17 were due to the lack of inclusion of the L3-4 vertebral interphase as prespecified.
For localized gastric cancer, preoperative chemoradiotherapy strategy achieved a pathCR rate of more than 20% in a cooperative group setting. The quality of surgery improved (50% with D2 dissection) possibly because surgery was part of this trial. With some refinements, this preoperative chemoradiotherapy strategy is poised for a randomized comparison with postoperative adjuvant chemoradiotherapy in patients with gastric cancer.

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    • "Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) can be performed in patients with early gastric cancer (EGC) to avoid further unnecessary invasive surgical procedures [3]. Neoadjuvant treatments have been investigated to achieve R0 resection for local advanced gastric cancer (AGC) [4]. Therefore, precision in preoperative staging is essential to the individualized stage-dependent treatment of gastric cancer and to the prognosis of patients with gastric cancer. "
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    ABSTRACT: This study compared the performance of endoscopic ultrasonography (EUS) and multislice spiral computed tomography (MSCT) in the preoperative staging of gastric cancer. A total of 610 patients participated in this study, all of whom had undergone surgical resection, had confirmed gastric cancer and were evaluated with EUS and MSCT. Tumor staging was evaluated using the Tumor-Node-Metastasis (TNM) staging and Japanese classification. The results from the imaging modalities were compared with the postoperative histopathological outcomes. The overall accuracies of EUS and MSCT for the T staging category were 76.7% and 78.2% (P=0.537), respectively. Stratified analysis revealed that the accuracy of EUS for T1 and T2 staging was significantly higher than that of MSCT (P<0.001 for both) and that the accuracy of MSCT in T3 and T4 staging was significantly higher than that of EUS (P<0.001 and 0.037, respectively). The overall accuracy of MSCT was 67.2% when using the 13th edition Japanese classification, and this percentage was significantly higher than the accuracy of EUS (49.3%) and MSCT (44.6%) when using the 6th edition UICC classification (P<0.001 for both values). Our results demonstrated that the overall accuracies of EUS and MSCT for preoperative staging were not significantly different. We suggest that a combination of EUS and MSCT is required for preoperative evaluation of TNM staging.
    PLoS ONE 11/2013; 8(11):e78846. DOI:10.1371/journal.pone.0078846 · 3.23 Impact Factor
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    • "Several studies have demonstrated better clinical and pathologic responses in locally advanced GCs recruiting preoperative chemoradiotherapy with experienced doses [4, 7, 8]. Neoadjuvant chemotherapy has considered as potential treatment opportunity for not only resectable GCs but also particularly eliminate micrometastases [9]. "
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    ABSTRACT: Background Early stage gastric cancer diagnosis has ensued different approaches in resection strategies. In order to increase the proportion of cases which have undergone radical resection or have reduced the recurrence rate, different pre-operative treatments have introduced. Here, we have verified an active preoperative chemotherapeutic regimen in locally advanced gastric cancer patients. Methods Forty nine patients who have found eligible to enter this phase 2 trial have treated with oxaliplatin 100 mg/m2 IV, docetaxel 50 mg/m2 IV, plus capecitabine 625 mg/m2 PO (TOX). Clinical staging has been following the first 2 cycles of induction chemotherapy. Patients that have further undergone radical surgery, have evaluated for pathological response rate. Results Anemia (10.2%), nausea (10.2%) and vomiting (6.1%) were the most frequent grade 3 or 4 adverse effects. Regarding the pathologic staging, 6 patients (12.2%) had complete response (95% CI 3% to 21.4%), 18 of them (36.7%) had partial response (95% CI 23.2% to 50.2%), then 3 patients (6.1%) had stable disease (95% CI 0%-12.8%). Among the patients who had surgery, 22% had pathologic complete response. Conclusion Preoperative chemotherapeutic regimen of TOX seems to be an active and safe neoadjuvant therapy in non metastatic gastric cancer. It should further be considered with concurrent radiotherapy.
    Iranian Journal of Cancer Prevention 03/2013; 6(3):133-140.
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    • "Previous studies could demonstrate that a docetaxelcontaining chemotherapy regimen is also an effective and tolerable treatment option in the neoadjuvant setting (Lorenzen et al, 2007; Biffi et al 2010; Sym et al, 2010; Homann et al, 2012; Thuss- Patience et al, 2012) where high anti-tumour activity, resulting in effective downstaging is required. In particular, neoadjuvant taxancontaining regimens can achieve promising complete pathological response rates (pCR) between 12 and 18% (Lorenzen et al, 2007; Biffi et al 2010; Homann et al, 2012), which is a known prognostic marker as patients with a pCR tend to have a much better outcome as underlined in recent studies (Ajani et al, 2006; Homann et al, 2012; Fields et al, 2012). Moreover, substitution of oxaliplatin for cisplatin has proven to be more tolerable and has shown improved efficacy in an exploratory subgroup analysis in patients aged X65 years with metastatic gastroesophageal adenocarcinoma (Al-Batran et al, 2008b). "
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    ABSTRACT: Background: The aim of this exploratory subgroup analysis of the fluorouracil, oxaliplatin, docetaxel (FLOT)65+ trial was to determine tolerability and feasibility of perioperative chemotherapy in elderly, potentially operable esophagogastric cancer patients. Methods: Patients aged ⩾65 with locally advanced esophagogastric adenocarcinoma were randomized to perioperative chemotherapy consisting of four pre- and four postoperative cycles of infusional 5-FU, leucovorin, and oxaliplatin (FLO) without or with docetaxel 50 mg m−2 (FLOT), every 2 weeks. Results: Forty-four patients with a median age of 70 years were randomized and 43 patients started preoperative chemotherapy (FLO, 22; FLOT, 21). Thirty-eight (86.4%) patients completed four cycles of preoperative chemotherapy and 32 (74.4%) proceeded to surgery, with 67.4% R0 resections on intent-to-treat analysis (90.1% of the 32 patients who underwent resection). Median overall survival was not reached and median progression-free survival (PFS) was 17.3 months. Compared with the FLO group, the FLOT group showed a trend towards an improved median PFS (21.1 vs 12.0 months; P=0.09), however, associated with increased chemotherapy related toxicity. No perioperative mortality was observed. Postoperative morbidity was observed in 46.9% of patients (FLO, 35.3% FLOT, 60%). Conclusion: Neoadjuvant FLO or FLOT may offer a reasonable chance of curative surgery in elderly patients with locally advanced resectable gastroesophageal cancer. However, the increase in side effects with the FLOT regimen and postoperative morbidity should be carefully considered when an intensive chemotherapy regimen is planned.
    British Journal of Cancer 01/2013; 108(3). DOI:10.1038/bjc.2012.588 · 4.84 Impact Factor
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