Practice Guidelines in Oncology - Gastric Cancer

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® Practice Guidelines NCCN in Oncology – v.1.2007 45,46 response that results in durable survival time. However, the value of such approaches needs to be determined in comparative trials. 47 Nonrandomized trials from Baeza and colleagues have reported encouraging results for patients with R0 resections who receive adjunctive treatment. Limited reports from randomized trials of postoperative RT with or without chemotherapy after a complete resection with negative margins did not reveal a clear survival 48,49 advantage. 23,50 The landmark trial is the Intergroup trial INT-0116. Eligibility included patients with T3 and/or N+ adenocarcinoma of the stomach or gastroesophageal junction. After a resection with negative margins, 603 patients were randomly assigned to either observation alone or postoperative combined modality therapy consisting of 5 monthly cycles of bolus chemotherapy with 45 Gy concurrent with cycles 2 and 3. There was a significant decrease in local failure as the first site of failure (19% versus 29%) as well as an increase in median survival (36 versus 27 months), 3-year relapse-free survival (48% versus 31%), and overall survival (50% versus 41%, P = .005) with combined modality therapy. The CALGB 80101 phase III trial is currently assessing postoperative standard therapy with 5- FU/leucovorin/radiation versus ECF (epirubicin, cisplatin, and 5- FU)/radiation ( http://www.nci.nih.gov/search/ViewClinicalTrials.aspx?cdrid=25878 7&version=patient&protocolsearchid=1575831). 51 Smalley and colleagues reviewed gastric anatomy and patterns of failure after surgery, and they offer detailed radiation treatment planning recommendations. A randomized trial by Zhang and associates from Beijing revealed a significant improvement in 52 survival with preoperative radiation (30% versus 20%, P = .0094). Gastric Cancer Manuscript update in progress Version 1.2007, 03/09/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index Gastric Table of Contents Staging, MS, References These data suggest that preoperative radiation improves local control and survival. However, randomized trials are needed to confirm these results in patients from the Western Hemisphere. The seminal trial examining the role of postoperative combined modality therapy in gastric cancer was reported by Moertel and 40 colleagues in 1969 (40 Gy versus 40 Gy plus 5-FU). This trial revealed a significant improvement in survival. The remaining randomized trials include patients with unresectable or residual cancer. None have shown a survival advantage. The use of intraoperative RT remains investigational. For resected gastric carcinoma, only 5-FU/leucovorin (category 1) has been studied in conjunction with RT in a phase III setting 23 (Intergroup 116). However, many participating institutions have developed other chemotherapy regimens in the context of phase II studies. Thus, these regimens represent institutional preferences, but they may not be superior to 5-FU/leucovorin. In the NCCN algorithm, preoperative chemoradiation options for localized, unresectable disease include 5-FU/leucovorin (category 1) as well as the following category 3 options such as 5-FU--based, cisplatinbased, taxane-based, and irinotecan-based regimens. Postoperative chemoradiation options include 5-FU/leucovorin (category 1) as well as the following category 3 options such as 5-FU/cisplatin, 5-FUbased, taxane-based, and ECF regimens. Chemotherapy Advanced gastric carcinoma is incurable, but chemotherapy can have a palliative effect in symptomatic patients. In four studies, combination chemotherapy resulted in better quality of life and overall survival when compared with best supportive care in patients 53-56 with advanced gastric carcinoma. However, all four studies only MS-5
® Practice Guidelines NCCN in Oncology – v.1.2007 had a small number of patients. Only a few single agents have established activity against advanced gastric carcinoma; these 57 58 agents include 5-FU, mitomycin, etoposide, and cisplatin. In the early 1980s, the FAM (5-FU, doxorubicin, and mitomycin) regimen was the gold standard therapy for patients with advanced 59 gastric carcinoma. In a pivotal study performed by the North 60 Central Cancer Treatment Group (NCCTG), the FAM regimen was compared with 5-FU as a single agent and 5-FU plus doxorubicin. No significant survival difference was detected among patients treated with these three regimens. However, response rates were higher with combination chemotherapy than with 5-FU alone. Thus, combination chemotherapy is preferable to single-agent therapy for palliation. Several randomized studies comparing FAM versus FAMTX (5-FU, 61 adriamycin, and methotrexate [with leucovorin rescue]), FAMTX 62 versus ECF, and FAMTX versus ELF (etoposide, leucovorin, and 5- 63 FU) versus 5-FU plus cisplatin have been reported in the past several years. No one standard therapy has emerged from these trials. Outside of clinical trials, the recommended chemotherapy for advanced gastric carcinoma is either cisplatin-based or 5-FU--based combination chemotherapy. Several drugs and their combinations have shown activity against 64-66 67-69 gastric carcinoma. The agents include paclitaxel, docetaxel, 70 71 irinotecan, UFT (a combination of uracil and tegafur), oral 72 73-77 etoposide, and S-1. In addition, combination chemotherapy 78-89 regimens have also been assessed. A number of oral agents also 81,82 hold promise in the treatment of gastric carcinoma. Agents that have not been extensively studied include capecitabine, oxaliplatin, and rubitecan. In addition, several new categories of agents are of Gastric Cancer Manuscript update in progress Version 1.2007, 03/09/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index Gastric Table of Contents Staging, MS, References interest, including vaccines, antireceptor agents, and antiangiogenic agents. A number of chemotherapy combinations are currently in 90,91 phase III trials, and we anticipate that a widely accepted front-line standard for patients with advanced gastric carcinoma might emerge 92 in the near future. For metastatic gastric carcinoma, there have been only a few phase III trials, which have assessed ECF, DCF (docetaxel/cisplatin/5-FU), and FOLFIRI-AIO (infusional 5- FU/leucovorin/irinotecan). However, participating institutions have developed chemotherapy regimens in the context of phase II studies . The regimens that have not been studied in the phase III setting may not be superior to DCF or ECF. In the NCCN algorithm, options for metastatic cancer include 5-FU/leucovorin (category 1) as well as the following category 3 options such as 5-FU--based (capecitabine), cisplatin-based, oxaliplatin-based, taxane-based, irinotecan-based, and ECF regimens. Moreover, many regimens may be considered as reference regimens in the first-line setting. There is no established second-line therapy for advanced gastric cancer. Workup In patients with gastric cancer, presenting symptoms can include anemia, early satiety, weight loss, and/or bleeding. Newly diagnosed patients should undergo a complete history, physical examination, chest x-ray, and endoscopy of the entire upper GI tract. A complete blood count (CBC), platelets, multichannel serum chemistry analysis (ie, SMA-12), coagulation studies, and a computed tomography (CT) scan of the abdomen should be performed; a positron emission tomography (PET) scan may also be useful, although there may be 93 false-positive results with PET. Combined PET/CT imaging is more 94 useful than either imaging alone for preoperative staging. In MS-6
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Practice Guidelines in Oncology - Gastric Cancer

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