Phase II Trial of Preoperative Chemoradiation in Patients With Localized Gastric Adenocarcinoma (RTOG 9904): Quality of Combined Modality Therapy and Pathologic Response
ABSTRACT 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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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 · 4.82 Impact Factor
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ABSTRACT: Despite a decline in its incidence in the Western world, gastric cancer (GC) remains the fourth most frequent cancer diagnosis worldwide and is, after lung cancer, the second leading cause of death from a malignant disease globally. Based on the published literature, treatment guidelines and reports from international meetings, we here review the current treatment options for GC and discuss insights and perspectives from the latest clinical studies. The management of GC in the early stages of the disease is based on an optimal surgical resection of the primary tumor and the regional lymph nodes. However, less than one third of patients have a resectable disease at diagnosis and among those operated, more than half are not cured by surgery alone, due to a high rate of relapse. Thus, for the majority of patients, systemic cytotoxic therapy, and sometimes radiotherapy, is a treatment option both as an adjunct to surgery and in the palliative setting. Adjuvant chemotherapy offers only a marginal benefit and has not become a standard of care in the West. In North America, adjuvant chemoradiation is broadly used, shown to significantly improve overall survival, albeit with the cost of high toxicity. Furthermore, a recently reported study from the United Kingdom demonstrated a significant disease-free and survival benefit by the use of perioperative combination chemotherapy. Several chemotherapeutic agents have been tested as a palliative therapy in advanced GC including 5- fluorouracil (5-FU), oral pyrimidines, platinum derivatives, anthracyclines, taxanes and camptothecans. It is now accepted that chemotherapy is better than best supportive care only and that 5-FU based combinations are more effective than monotherapy. However, the response rates have generally been moderate and there is no consensus on the optimal combination of cytotoxic agents and the potential role of more recently developed "targeted therapies".Acta Oncologica 02/2007; 46(3):277-85. DOI:10.1080/02841860701218634 · 3.71 Impact Factor
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ABSTRACT: The purpose of this study was to determine if international guidelines differ in their recommendations concerning additive therapy for advanced, but potentially curable, gastric cancer. A systematic search of the English and German literature was conducted in the databases Medline, Cochrane Database, Embase, and PubMed. The search terms used were 'guidelines gastric cancer,' 'guidelines stomach cancer,' and 'Leitlinien Magenkarzinom.' Six different guidelines published after January 1, 2010, in which the tumors were classified according to the seventh edition of the TNM system (2010), were identified. Although the examined guidelines were based on the same study results, their recommendations concerning accompanying therapy for gastric cancer differ considerably. While perioperative chemotherapy is recommended in Germany, Great Britain, and large parts of Europe, postoperative adjuvant radiochemotherapy or perioperative chemotherapy is recommended in the USA and Canada. In Japan, postoperative adjuvant chemotherapy is recommended.The results of identical studies were interpreted differently in different countries. Since considerable effort is required for each country to separately test relevant studies for their validity and suitability, an international cooperation could simplify the creation of a common basis for guidelines and contribute to improved comparability of international guidelines.03/2015; 15(1):10-18. DOI:10.5230/jgc.2015.15.1.10