Skip to main content
Top
Published in: Annals of Surgical Oncology 3/2015

01-12-2015 | Gastrointestinal Oncology

Influence of Different Neoadjuvant Chemotherapy Regimens on Response, Prognosis, and Complication Rate in Patients with Esophagogastric Adenocarcinoma

Authors: Christoph Springfeld, MD, PhD, Christiane Wiecha, Romy Kunzmann, Ulrike Heger, MD, Wilko Weichert, MD, Rupert Langer, MD, Annika Stange, MD, Susanne Blank, MD, Leila Sisic, MD, Thomas Schmidt, MD, PhD, Florian Lordick, MD, Dirk Jäger, MD, Lars Grenacher, MD, Tom Bruckner, PhD, Markus W. Büchler, MD, Katja Ott, MD

Published in: Annals of Surgical Oncology | Special Issue 3/2015

Login to get access

Abstract

Background

Perioperative chemotherapy improves survival in patients with advanced esophagogastric cancer, but the optimal treatment regimen remains unclear. More intensive chemotherapy may improve outcome, but also increase toxicity and complications.

Methods

A total of 843 patients were included in this retrospective study and stratified in 4 groups: doublet therapy with cisplatin or oxaliplatin and 5-fluorouracil (groups A/B) or triplet therapy with additional epirubicin or taxane (groups C/D). The influence of the different neoadjuvant chemotherapy regimens on response, prognosis, and complications was assessed.

Results

Clinical and pathological response were associated with longer overall survival (OS; p < 0.001). No significant differences regarding response or OS were found, but there was a trend toward better outcome in group D (taxane-containing triplet). In the subgroup of 669 patients with adenocarcinomas of the esophagogastric junction (AEG), patients who had received taxane-containing regimens had a significantly longer OS (p = 0.037), but taxane use was not an independent factor in multivariate analysis. Triple therapy with taxanes did not result in a higher complication rate or postoperative mortality.

Conclusions

Although no superior neoadjuvant chemotherapy regimen was identified for patients with esophagogastric adenocarcinoma, taxane-containing regimens should be further investigated in randomized trials, especially in patients with AEG tumors.
Literature
2.
3.
4.
go back to reference Wilke H, Lordick F, Meyer HJ, Stahl M. (Neo)-adjuvant chemo(-radio) therapy for adenocarcinomas of the gastroesophageal junction and the stomach in the West. Dig Surg. 2013;30:112–8.PubMedCrossRef Wilke H, Lordick F, Meyer HJ, Stahl M. (Neo)-adjuvant chemo(-radio) therapy for adenocarcinomas of the gastroesophageal junction and the stomach in the West. Dig Surg. 2013;30:112–8.PubMedCrossRef
5.
go back to reference Sehdev A, Catenacci DV. Perioperative therapy for locally advanced gastroesophageal cancer: current controversies and consensus of care. J Hematol Oncol. 2013;6:66.PubMedPubMedCentralCrossRef Sehdev A, Catenacci DV. Perioperative therapy for locally advanced gastroesophageal cancer: current controversies and consensus of care. J Hematol Oncol. 2013;6:66.PubMedPubMedCentralCrossRef
6.
go back to reference Okines A, Verheij M, Allum W, Cunningham D, Cervantes A. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v50–v54.PubMedCrossRef Okines A, Verheij M, Allum W, Cunningham D, Cervantes A. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v50–v54.PubMedCrossRef
7.
go back to reference Lutz MP, Zalcberg JR, Ducreux M, et al. Highlights of the EORTC St. Gallen International Expert Consensus on the primary therapy of gastric, gastroesophageal and oesophageal cancer—differential treatment strategies for subtypes of early gastroesophageal cancer. Eur J Cancer. 2012;48:2941–53.PubMedCrossRef Lutz MP, Zalcberg JR, Ducreux M, et al. Highlights of the EORTC St. Gallen International Expert Consensus on the primary therapy of gastric, gastroesophageal and oesophageal cancer—differential treatment strategies for subtypes of early gastroesophageal cancer. Eur J Cancer. 2012;48:2941–53.PubMedCrossRef
8.
go back to reference Ajani JA, Bentrem DJ, Besh S, et al. Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines. J Natl Compr Cancer Netw. 2013;11:531–46. Ajani JA, Bentrem DJ, Besh S, et al. Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines. J Natl Compr Cancer Netw. 2013;11:531–46.
9.
go back to reference Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.PubMedCrossRef Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.PubMedCrossRef
10.
go back to reference Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29:1715–21.PubMedCrossRef Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29:1715–21.PubMedCrossRef
11.
go back to reference van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.PubMedCrossRef van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.PubMedCrossRef
12.
go back to reference Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.PubMedCrossRef Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.PubMedCrossRef
13.
go back to reference Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, Fleig WE. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2010;3:CD004064.PubMed Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, Fleig WE. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2010;3:CD004064.PubMed
14.
go back to reference Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006;24:4991–7.PubMedCrossRef Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006;24:4991–7.PubMedCrossRef
15.
go back to reference Al-Batran SE, Hartmann JT, Hofheinz R, et al. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2008;19:1882–7.PubMedCrossRef Al-Batran SE, Hartmann JT, Hofheinz R, et al. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2008;19:1882–7.PubMedCrossRef
16.
go back to reference Lorenzen S, Hentrich M, Haberl C, et al. Split-dose docetaxel, cisplatin and leucovorin/fluorouracil as first-line therapy in advanced gastric cancer and adenocarcinoma of the gastroesophageal junction: results of a phase II trial. Ann Oncol. 2007;18:1673–9.PubMedCrossRef Lorenzen S, Hentrich M, Haberl C, et al. Split-dose docetaxel, cisplatin and leucovorin/fluorouracil as first-line therapy in advanced gastric cancer and adenocarcinoma of the gastroesophageal junction: results of a phase II trial. Ann Oncol. 2007;18:1673–9.PubMedCrossRef
17.
go back to reference Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014;15:640–7.PubMedCrossRef Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014;15:640–7.PubMedCrossRef
18.
go back to reference Heger U, Bader F, Lordick F, et al. Interim endoscopy results during neoadjuvant therapy for gastric cancer correlate with histopathological response and prognosis. Gastric Cancer. 2014;17:478–88.PubMedCrossRef Heger U, Bader F, Lordick F, et al. Interim endoscopy results during neoadjuvant therapy for gastric cancer correlate with histopathological response and prognosis. Gastric Cancer. 2014;17:478–88.PubMedCrossRef
19.
go back to reference Ott K, Sendler A, Becker K, et al. Neoadjuvant chemotherapy with cisplatin, 5-FU, and leucovorin (PLF) in locally advanced gastric cancer: a prospective phase II study. Gastric Cancer. 2003;6:159–67.PubMedCrossRef Ott K, Sendler A, Becker K, et al. Neoadjuvant chemotherapy with cisplatin, 5-FU, and leucovorin (PLF) in locally advanced gastric cancer: a prospective phase II study. Gastric Cancer. 2003;6:159–67.PubMedCrossRef
20.
go back to reference Lordick F, Ott K, Krause BJ, et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007;8:797–805.PubMedCrossRef Lordick F, Ott K, Krause BJ, et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007;8:797–805.PubMedCrossRef
21.
go back to reference Al-Batran SE, Hartmann JT, Probst S, et al. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008;26:1435–42.PubMedCrossRef Al-Batran SE, Hartmann JT, Probst S, et al. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008;26:1435–42.PubMedCrossRef
22.
go back to reference Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36–46.PubMedCrossRef Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36–46.PubMedCrossRef
23.
go back to reference Bader FG, Lordick F, Fink U, et al. Paclitaxel in the neoadjuvant treatment for adeno carcinoma of the distal esophagus (AEG I). A comparison of two phase II trials with long-term follow-up. Onkologie. 2008;3:366–72.CrossRef Bader FG, Lordick F, Fink U, et al. Paclitaxel in the neoadjuvant treatment for adeno carcinoma of the distal esophagus (AEG I). A comparison of two phase II trials with long-term follow-up. Onkologie. 2008;3:366–72.CrossRef
24.
go back to reference Becker K, Mueller JD, Schuhmacher C, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003;98:1521–30.PubMedCrossRef Becker K, Mueller JD, Schuhmacher C, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003;98:1521–30.PubMedCrossRef
25.
go back to reference Fields RC, Strong VE, Gonen M, et al. Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma. Br J Cancer. 2011;104:1840–7.PubMedPubMedCentralCrossRef Fields RC, Strong VE, Gonen M, et al. Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma. Br J Cancer. 2011;104:1840–7.PubMedPubMedCentralCrossRef
26.
go back to reference Ott K, Blank S, Becker K, et al. Factors predicting prognosis and recurrence in patients with esophago-gastric adenocarcinoma and histopathological response with less than 10 % residual tumor. Langenbecks Arch Surg. 2013;398:239–49.PubMedCrossRef Ott K, Blank S, Becker K, et al. Factors predicting prognosis and recurrence in patients with esophago-gastric adenocarcinoma and histopathological response with less than 10 % residual tumor. Langenbecks Arch Surg. 2013;398:239–49.PubMedCrossRef
27.
go back to reference Vallböhmer H, Hölscher AH, DeMeester S, et al. A multicenter study of survival after neoadjuvant radiotherapy/chemotherapy and esophagectomy for ypT0N0M0R0 esophageal cancer. Ann Surg. 2010;252:744–9.PubMedCrossRef Vallböhmer H, Hölscher AH, DeMeester S, et al. A multicenter study of survival after neoadjuvant radiotherapy/chemotherapy and esophagectomy for ypT0N0M0R0 esophageal cancer. Ann Surg. 2010;252:744–9.PubMedCrossRef
29.
go back to reference Fink U, Schuhmacher C, Stein HJ, et al. Preoperative chemotherapy for stage III–IV gastric carcinoma: feasibility, response and outcome after complete resection. Br J Surg. 1995; 82:1248–52.PubMedCrossRef Fink U, Schuhmacher C, Stein HJ, et al. Preoperative chemotherapy for stage III–IV gastric carcinoma: feasibility, response and outcome after complete resection. Br J Surg. 1995; 82:1248–52.PubMedCrossRef
30.
go back to reference Schuhmacher CP, Fink U, Becker K, Busch R, Dittler HJ, Mueller J, Siewert JR. Neoadjuvant therapy for patients with locally advanced gastric carcinoma with etoposide, doxorubicin, and cisplatinum. Closing results after 5 years of follow-up. Cancer. 2001;91:918–27.PubMedCrossRef Schuhmacher CP, Fink U, Becker K, Busch R, Dittler HJ, Mueller J, Siewert JR. Neoadjuvant therapy for patients with locally advanced gastric carcinoma with etoposide, doxorubicin, and cisplatinum. Closing results after 5 years of follow-up. Cancer. 2001;91:918–27.PubMedCrossRef
31.
go back to reference Lorenzen S, Blank S, Lordick F, Siewert JR, Ott K. Prediction of response and prognosis by a score including only pretherapeutic parameters in 410 neoadjuvant treated gastric cancer patients. Ann Surg Oncol. 2012;19:2119–27.PubMedCrossRef Lorenzen S, Blank S, Lordick F, Siewert JR, Ott K. Prediction of response and prognosis by a score including only pretherapeutic parameters in 410 neoadjuvant treated gastric cancer patients. Ann Surg Oncol. 2012;19:2119–27.PubMedCrossRef
32.
go back to reference Reim D, Gertler R, Novotny A, et al. Adenocarcinomas of the esophagogastric junction are more likely to respond to preoperative chemotherapy than distal gastric cancer. Ann Surg Oncol. 2012;19:2108–18.PubMedCrossRef Reim D, Gertler R, Novotny A, et al. Adenocarcinomas of the esophagogastric junction are more likely to respond to preoperative chemotherapy than distal gastric cancer. Ann Surg Oncol. 2012;19:2108–18.PubMedCrossRef
33.
go back to reference Ronellenfitsch U, Schwarzbach M, Hofheinz R, et al. Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: systematic review with meta-analysis combining individual patient and aggregate data. Eur J Cancer. 2013;49:3149–58.PubMedCrossRef Ronellenfitsch U, Schwarzbach M, Hofheinz R, et al. Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: systematic review with meta-analysis combining individual patient and aggregate data. Eur J Cancer. 2013;49:3149–58.PubMedCrossRef
34.
go back to reference Becker K, Langer R, Reim D, et al. Significance of histopathological tumor regression after neoadjuvant chemotherapy in gastric adenocarcinomas: a summary of 480 cases. Ann Surg. 2011;253:934–9.PubMedCrossRef Becker K, Langer R, Reim D, et al. Significance of histopathological tumor regression after neoadjuvant chemotherapy in gastric adenocarcinomas: a summary of 480 cases. Ann Surg. 2011;253:934–9.PubMedCrossRef
35.
go back to reference Lowy AM, Mansfield PF, Leach SD, Pazdur R, Dumas P, Ajani JA. Response to neoadjuvant chemotherapy best predicts survival after curative resection of gastric cancer. Ann Surg. 1999;229:303–8.PubMedPubMedCentralCrossRef Lowy AM, Mansfield PF, Leach SD, Pazdur R, Dumas P, Ajani JA. Response to neoadjuvant chemotherapy best predicts survival after curative resection of gastric cancer. Ann Surg. 1999;229:303–8.PubMedPubMedCentralCrossRef
36.
go back to reference Lorenzen S, Thuss-Patience P, Al-Batran SE, et al. Impact of pathologic complete response on disease-free survival in patients with esophagogastric adenocarcinoma receiving preoperative docetaxel-based chemotherapy. Ann Oncol. 2013;24:2068–73.PubMedCrossRef Lorenzen S, Thuss-Patience P, Al-Batran SE, et al. Impact of pathologic complete response on disease-free survival in patients with esophagogastric adenocarcinoma receiving preoperative docetaxel-based chemotherapy. Ann Oncol. 2013;24:2068–73.PubMedCrossRef
37.
go back to reference Langer R, Ott K, Feith M, Lordick F, Siewert JR, Becker K. Prognostic significance of histopathological tumor regression after neoadjuvant chemotherapy in esophageal adenocarcinomas. Mod Pathol. 2009;22:1555–63.PubMedCrossRef Langer R, Ott K, Feith M, Lordick F, Siewert JR, Becker K. Prognostic significance of histopathological tumor regression after neoadjuvant chemotherapy in esophageal adenocarcinomas. Mod Pathol. 2009;22:1555–63.PubMedCrossRef
38.
go back to reference Homann N, Pauligk C, Luley K, et al. Pathological complete remission in patients with oesophagogastric cancer receiving preoperative 5-fluorouracil, oxaliplatin and docetaxel. Int J Cancer. 2012;130:1706–13.PubMedCrossRef Homann N, Pauligk C, Luley K, et al. Pathological complete remission in patients with oesophagogastric cancer receiving preoperative 5-fluorouracil, oxaliplatin and docetaxel. Int J Cancer. 2012;130:1706–13.PubMedCrossRef
39.
go back to reference Schuhmacher C, Gretschel S, Lordick F, et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010;28:5210–8.PubMedPubMedCentralCrossRef Schuhmacher C, Gretschel S, Lordick F, et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010;28:5210–8.PubMedPubMedCentralCrossRef
Metadata
Title
Influence of Different Neoadjuvant Chemotherapy Regimens on Response, Prognosis, and Complication Rate in Patients with Esophagogastric Adenocarcinoma
Authors
Christoph Springfeld, MD, PhD
Christiane Wiecha
Romy Kunzmann
Ulrike Heger, MD
Wilko Weichert, MD
Rupert Langer, MD
Annika Stange, MD
Susanne Blank, MD
Leila Sisic, MD
Thomas Schmidt, MD, PhD
Florian Lordick, MD
Dirk Jäger, MD
Lars Grenacher, MD
Tom Bruckner, PhD
Markus W. Büchler, MD
Katja Ott, MD
Publication date
01-12-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4617-x

Other articles of this Special Issue 3/2015

Annals of Surgical Oncology 3/2015 Go to the issue