Периоперационная химиотерапия рака желудка: состояние проблемы
Периоперационная химиотерапия рака желудка: состояние проблемы
Лядов В.К., Пардабекова О.А., Лядова М.А. Периоперационная химиотерапия рака желудка: состояние проблемы. Современная Онкология. 2018; 20 (2): 56–60. DOI: 10.26442/1815-1434_2018.2.56-60
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Lyadov V.K., Pardabekova O.A., Lyadova M.A. Perioperative chemotherapy for gastric cancer: the current state. Journal of Modern Oncology. 2018; 20 (2): 56–60. DOI: 10.26442/1815-1434_2018.2.56-60
Периоперационная химиотерапия рака желудка: состояние проблемы
Лядов В.К., Пардабекова О.А., Лядова М.А. Периоперационная химиотерапия рака желудка: состояние проблемы. Современная Онкология. 2018; 20 (2): 56–60. DOI: 10.26442/1815-1434_2018.2.56-60
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Lyadov V.K., Pardabekova O.A., Lyadova M.A. Perioperative chemotherapy for gastric cancer: the current state. Journal of Modern Oncology. 2018; 20 (2): 56–60. DOI: 10.26442/1815-1434_2018.2.56-60
Рак желудка занимает одну из лидирующих позиций в мире по распространенности и смертности среди злокачественных новообразований. Результаты хирургического лечения местно-распространенного рака желудка неудовлетворительны в связи с высокой частотой прогрессирования после операции. В настоящее время периоперационная (до- и послеоперационная) химиотерапия в сочетании с радикальным оперативным вмешательством рекомендована пациентам, страдающим раком желудка IB–III стадии. Мы провели анализ исследований, посвященных проблеме выбора оптимального режима периоперационной химиотерапии при местно-распространенном и олигометастатическом раке желудка. Наибольшая эффективность отмечена у таксансодержащего режима FLOТ, применение которого в рамках рандомизированного многоцентрового исследования III фазы позволило увеличить медиану общей выживаемости пациентов до 50 мес. Применение периоперационной химиотерапии в сочетании с анти-Her2-терапией, иммунотерапией или любым другим биологически направленным препаратом возможно лишь в рамках клинических исследований.
Gastric cancer has one of the leading positions in the world in the prevalence and mortality among malignant tumors. The results of surgical treatment of locally advanced gastric cancer remain generally poor due to the high rate of relapse after surgery. Currently, perioperative (pre- and postoperative) chemotherapy in combination with surgery is recommended for patients with stage ≥IB resectable gastric cancer. We analyzed the studies devoted to the problem of choosing the optimal regimen of perioperative chemotherapy in locally advanced and oligometastatic gastric cancer. The highest efficacy was observed in the taxan-containing regimen FLOT which allowed to increase the median overall survival up to 50 months in a randomized controlled phase III trial. The use of perioperative chemotherapy with anti-Her2 therapy, immunotherapy or any other biologic drug remains investigational.
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4. Smyth EC, Verheij M, Allum W et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27 (5): v38–v49.
5. Cartwright E, Cunningham D. The Role of Systemic Therapy in Resectable Gastric and Gastro-oesophageal Junction Cancer. Curr Treat Options Oncol 2017; 18: 69.
6. 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.
7. Smyth EC, Fassan M, Cunningham D et al. Effect of pathologic tumor response and nodal status on survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy trial. J Clin Oncol 2016; 34 (23): 2721–7.
8. Smyth EC, Wotherspoon A, Peckitt C et al. Mismatch repair deficiency, microsatellite instability, and survival: an exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. JAMA Oncol 2017.
9. 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.
10. Alderson D, Cunningham D, Nankivell M et al. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial. Lancet Oncol 2017; 18 (9): 1249–60.
11. Ferri LE, Ades S, Alcindor T et al. Perioperative docetaxel, cisplatin, and 5-fluorouracil (DCF) for locally advanced esophageal and gastric adenocarcinoma: a multicenter phase II trial. Ann Oncol 2012; 23 (6): 1512–7.
12. Thuss-Patience PC, Hofheinz RD, Arnold D et al. Perioperative chemotherapy with docetaxel, cisplatin and capecitabine (DCX) in gastro-oesophageal adenocarcinoma: a phase II study of the arbeitsgemeinschaft internistische onkologie (AIO){dagger}. Ann Oncol 2012; 23: 2827–34.
13. Biffi R, Fazio N, Luca F et al. Surgical outcome after docetaxel-based neoadjuvant chemotherapy in locally-advanced gastric cancer. World J Gastroenterol 2010; 16: 868–74.
14. Schulz C, Kullmann F, Kunzmann V. NeoFLOT: Multicenter phase II study of perioperative chemotherapy in resectable adenocarcinoma of the gastroesophageal junction or gastric adenocarcinoma-Very good response predominantly in patients with intestinal type tumors. Int J Cancer 2015; 137 (3): 678–85.
15. Lorenzen S, Pauligk C, Homann N. Feasibility of perioperative chemotherapy with infusional 5-FU, leucovorin, and oxaliplatin with (FLOT) or without (FLO) docetaxel in elderly patients with locally advanced esophagogastric cancer. Br J Cancer 2013; 108 (3): 519–26.
16. Al-Batran SE, Hofheinz RD, Pauligk C et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol 2016; 17 (12): 1697–708.
17. Al-Batran SE, Homann N, Schmalenberg H et al. Peri-operative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): a multicenter, randomized phase 3 trial. J Clin Oncol 2017; 35 (Suppl. 15): 4004.
18. 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 (8): 2068–73.
19. Al-Batran S-E, zur Hausen G, NCT02581462 – FLOT vs. FLOT/herceptin/pertuzumab for perioperative therapy of adenocarcinoma of the stomach and gastroesophageal junction expressing HER-2.
A phase II/III trial of the AIO. https://clinicaltrials.gov/ ct2/show/ NCT02581462
20. Bang YJ, Van Cutsem E, Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, openlabel, randomized controlled trial. Lancet 2010; 376 (9742): 687–97.
21. Wagner AD. NCT02205047 – neoadjuvant study using trastuzumab or trastuzumab with pertuzumab in gastric or gastroesophageal junction adenocarcinoma (INNOVATION). https://clinical trials.gov/ct2/show/NCT02205047
22. Cunningham D, Stenning SP, Smyth EC et al. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2–3 trial. Lancet Oncol 2017; 18: 357–70.
23. Al-Batran S-E, Bankstahl US. NCT02661971 – perioperative ramucirumab in combination with FLOT versus FLOT alone for resectable esophagogastric adenocarcinoma – RAMSES – a phase II/III trial of the AIO. https://clinicaltrials.gov/ct2/show/ NCT02661971
24. Sun W. NCT02943603 – a study of perioperative mFOLFOX6 plus pembrolizumab in patients with potentially resectable adenocarcinoma of the gastroesophageal junction (GEJ) and stomach. https://clinicaltrials.gov/ct2/show/NCT02943603
25. Otap D, Shah M, Oberstein P. NCT02918162 – perioperative chemo and pembrolizumab in gastric cancer. https://clinicaltrials.gov/ ct2/show/NCT02918162
26. Fujitani K, Yang H-K, Mizusawa J et al. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol 2016; 17: 309–18.
27. Al-Batran SE, Homann N, Pauligk C et al. Effect of neoadjuvant chemotherapy followed by surgical resection on survival in patients with limited metastatic gastric or gastroesophageal junction cancer: the AIO-FLOT3 trial. JAMA Oncol 2017.
28. Al-Batran SE, Goetze TO, Mueller DW et al. The RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction – a phase III trial of the German AIO/CAO-V/CAOGI. BMC Cancer 2017; 17 (1): 893.
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1. Ferlay J, Soerjomataram I, Ervik M et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11, International Agency for Research on Cancer, Lyon, France, 2014.
2. Kaprin A.D., Starinskii V.V., Petrova G.V. Sostoianie onkologicheskoi pomoshchi naseleniiu Rossii v 2016 godu. M.: MNIOI im. P.A.Gertsena filial FGBU «NMIRTs» Minzdrava Rossii, 2017. [in Russian]
3. Davydov M.I., Aksel E.M. Statistika zlokachestvennykh novoobrazovanii v Rossii i stranakh SNG v 2013 g. M., 2015. [in Russian]
4. Smyth EC, Verheij M, Allum W et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27 (5): v38–v49.
5. Cartwright E, Cunningham D. The Role of Systemic Therapy in Resectable Gastric and Gastro-oesophageal Junction Cancer. Curr Treat Options Oncol 2017; 18: 69.
6. 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.
7. Smyth EC, Fassan M, Cunningham D et al. Effect of pathologic tumor response and nodal status on survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy trial. J Clin Oncol 2016; 34 (23): 2721–7.
8. Smyth EC, Wotherspoon A, Peckitt C et al. Mismatch repair deficiency, microsatellite instability, and survival: an exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. JAMA Oncol 2017.
9. 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.
10. Alderson D, Cunningham D, Nankivell M et al. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial. Lancet Oncol 2017; 18 (9): 1249–60.
11. Ferri LE, Ades S, Alcindor T et al. Perioperative docetaxel, cisplatin, and 5-fluorouracil (DCF) for locally advanced esophageal and gastric adenocarcinoma: a multicenter phase II trial. Ann Oncol 2012; 23 (6): 1512–7.
12. Thuss-Patience PC, Hofheinz RD, Arnold D et al. Perioperative chemotherapy with docetaxel, cisplatin and capecitabine (DCX) in gastro-oesophageal adenocarcinoma: a phase II study of the arbeitsgemeinschaft internistische onkologie (AIO){dagger}. Ann Oncol 2012; 23: 2827–34.
13. Biffi R, Fazio N, Luca F et al. Surgical outcome after docetaxel-based neoadjuvant chemotherapy in locally-advanced gastric cancer. World J Gastroenterol 2010; 16: 868–74.
14. Schulz C, Kullmann F, Kunzmann V. NeoFLOT: Multicenter phase II study of perioperative chemotherapy in resectable adenocarcinoma of the gastroesophageal junction or gastric adenocarcinoma-Very good response predominantly in patients with intestinal type tumors. Int J Cancer 2015; 137 (3): 678–85.
15. Lorenzen S, Pauligk C, Homann N. Feasibility of perioperative chemotherapy with infusional 5-FU, leucovorin, and oxaliplatin with (FLOT) or without (FLO) docetaxel in elderly patients with locally advanced esophagogastric cancer. Br J Cancer 2013; 108 (3): 519–26.
16. Al-Batran SE, Hofheinz RD, Pauligk C et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol 2016; 17 (12): 1697–708.
17. Al-Batran SE, Homann N, Schmalenberg H et al. Peri-operative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): a multicenter, randomized phase 3 trial. J Clin Oncol 2017; 35 (Suppl. 15): 4004.
18. 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 (8): 2068–73.
19. Al-Batran S-E, zur Hausen G, NCT02581462 – FLOT vs. FLOT/herceptin/pertuzumab for perioperative therapy of adenocarcinoma of the stomach and gastroesophageal junction expressing HER-2.
A phase II/III trial of the AIO. https://clinicaltrials.gov/ ct2/show/ NCT02581462
20. Bang YJ, Van Cutsem E, Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, openlabel, randomized controlled trial. Lancet 2010; 376 (9742): 687–97.
21. Wagner AD. NCT02205047 – neoadjuvant study using trastuzumab or trastuzumab with pertuzumab in gastric or gastroesophageal junction adenocarcinoma (INNOVATION). https://clinical trials.gov/ct2/show/NCT02205047
22. Cunningham D, Stenning SP, Smyth EC et al. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2–3 trial. Lancet Oncol 2017; 18: 357–70.
23. Al-Batran S-E, Bankstahl US. NCT02661971 – perioperative ramucirumab in combination with FLOT versus FLOT alone for resectable esophagogastric adenocarcinoma – RAMSES – a phase II/III trial of the AIO. https://clinicaltrials.gov/ct2/show/ NCT02661971
24. Sun W. NCT02943603 – a study of perioperative mFOLFOX6 plus pembrolizumab in patients with potentially resectable adenocarcinoma of the gastroesophageal junction (GEJ) and stomach. https://clinicaltrials.gov/ct2/show/NCT02943603
25. Otap D, Shah M, Oberstein P. NCT02918162 – perioperative chemo and pembrolizumab in gastric cancer. https://clinicaltrials.gov/ ct2/show/NCT02918162
26. Fujitani K, Yang H-K, Mizusawa J et al. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol 2016; 17: 309–18.
27. Al-Batran SE, Homann N, Pauligk C et al. Effect of neoadjuvant chemotherapy followed by surgical resection on survival in patients with limited metastatic gastric or gastroesophageal junction cancer: the AIO-FLOT3 trial. JAMA Oncol 2017.
28. Al-Batran SE, Goetze TO, Mueller DW et al. The RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction – a phase III trial of the German AIO/CAO-V/CAOGI. BMC Cancer 2017; 17 (1): 893.
Авторы
В.К.Лядов*1,2, О.А.Пардабекова2, М.А.Лядова2
1 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России. 121552, Россия, Москва, ул. 3-я Черепковская, д. 15а;
2 Клиническая больница №1 МЕДСИ. 143442, Россия, Московская обл., Красногорский р-н, Пятницкое ш., 6-й км
*vlyadov@gmail.com
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V.K.Lyadov*1,2, O.A.Pardabekova2, M.A.Lyadova2
1 Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation. 121552, Russian Federation, Moscow, 3-ia Cherepkovskaia, d. 15a;
2 Clinical Hospital №1 MEDSI. 143442, Russian Federation, Moskovskaia obl., Krasnogorskii r-n, Piatnitskoe sh., 6-i km
*vlyadov@gmail.com