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Системная лекарственная терапия метастатического рака поджелудочной железы
Системная лекарственная терапия метастатического рака поджелудочной железы
И.А.Покатаев, С.А.Тюляндин. Системная лекарственная терапия метастатического рака поджелудочной железы. Современная онкология. 2016; 18 (1): 20–24.
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Аннотация
До 2011 г. стандартом лечения больных местнораспространенным и метастатическим раком поджелудочной железы была монохимиотерапия гемцитабином. Попытки создания комбинаций гемцитабина с новыми лекарственными препаратами длительное время не приводили к клинически значимому увеличению продолжительности жизни этих больных. Внедрение в клиническую практику новых режимов химиотерапии – комбинации nab-паклитаксела и FOLFIRINOX – привело к клинически значимому увеличению продолжительности жизни. Особенности проведения и спектр токсичности новых режимов химиотерапии позволяют сформировать алгоритм выбора режима химиотерапии для каждого пациента на основании его состояния, сопутствующей патологии и осложнений опухолевого процесса.
Ключевые слова: рак поджелудочной железы, химиотерапия, абраксан, NAB-паклитаксел, FOLFIRINOX.
Key words: pancreatic cancer, chemotherapy, abraksan, NAB-paclitaxel, FOLFIRINOX.
Ключевые слова: рак поджелудочной железы, химиотерапия, абраксан, NAB-паклитаксел, FOLFIRINOX.
________________________________________________
Key words: pancreatic cancer, chemotherapy, abraksan, NAB-paclitaxel, FOLFIRINOX.
Полный текст
Список литературы
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5. Louvet C, Labianca R, Hammel P et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 2005; 23: 3509–16.
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7. Rocha Lima CM, Green MR, Rotche R et al. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol 2004; 22: 3776–83.
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9. Philip PA, Benedetti J, Corless CL et al. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol 2010; 28: 3605–10.
10. Kindler HL, Niedzwiecki D, Hollis D et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol 2010; 28: 3617–22.
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13. Kindler HL, Richards DA, Garbo LE et al. A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer. Ann Oncol 2012; 23: 2834–42.
14. Bodoky G, Timcheva C, Spigel DR et al. A phase II open-label random-ized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy. Invest New Drugs 2012; 30: 1216–23.
15. Wolpin BM, Hezel AF, Abrams T et al. Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J Clin Oncol 2009; 27: 193–8.
16. Royal RE, Levy C, Turner K et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother 2010; 33: 828–33.
17. Wolpin BM, O’Reilly EM, Ko YJ et al. Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer. Ann Oncol 2013; 24: 1792–801.
18. Grubbs SS, Grusenmeyer PA, Petrelli NJ, Gralla RJ. Is it cost-effective to add erlotinib to gemcitabine in advanced pancreatic cancer? J Clin Oncol 2006; 24 (18S): 6048.
19. Conroy T, Desseigne F, Ychou M et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364 (19): 1817–25.
20. Marsh Rde W, Talamonti MS, Katz MH, Herman JM. Pancreatic cancer and FOLFIRINOX: a new era and new questions. Cancer Med 2015; 4 (6): 853–63.
21. Desai N, Trieu V et al. Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res 2006; 12: 1317–24.
22. Von Hoff, D, Ramanathan R, Borad M et al. Gemcitabine Plus nab-Paclitaxel Is an Active Regimen in Patients With Advanced Pancreatic Cancer: A Phase I/II Trial. J Clin Oncol 2011; 36: 5742.
23. Von Hoff DD, Ramanathan R, Borad M et al. SPARC correlation with response to gemcitabine (G) plus nab-paclitaxel (nab-P) in patients with advanced metastatic pancreatic cancer: A phase I/II study. J Clin Oncol 2009; 27 (Suppl.): 4525.
24. Von Hoff DD, Ervin T, Arena FP et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369 (18): 1691–703.
25. Goldstein D, El-Maraghi RH, Hammel P et al. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. J Natl Cancer Inst 2015; 107 (2).
2. Burris AH, Moore MJ, Andersen J et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997; 15: 2403–13.
3. Berlin JD, Catalano P, Thomas JP et al. Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 2002; 20: 3270–5.
4. Bernhard J, Dietrich D, Scheithauer W et al. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol 2008; 26: 3695–701.
5. Louvet C, Labianca R, Hammel P et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 2005; 23: 3509–16.
6. Colucci G, Labianca R, Di Costanzo F et al. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol 2010; 28: 1645–5.
7. Rocha Lima CM, Green MR, Rotche R et al. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol 2004; 22: 3776–83.
8. Oettle H, Richards D, Ramanathan RK et al. A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer. Ann Oncol 2005; 16: 1639–45.
9. Philip PA, Benedetti J, Corless CL et al. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol 2010; 28: 3605–10.
10. Kindler HL, Niedzwiecki D, Hollis D et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol 2010; 28: 3617–22.
11. Moore MJ, Goldstein D, Hamm J et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007; 25: 1960–6.
12. Rougier P, Riess H, Manges R et al. Randomised, placebo-controlled, double-blind, parallelgroup phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. Eur J Cancer 2013; 49: 2633–42.
13. Kindler HL, Richards DA, Garbo LE et al. A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer. Ann Oncol 2012; 23: 2834–42.
14. Bodoky G, Timcheva C, Spigel DR et al. A phase II open-label random-ized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy. Invest New Drugs 2012; 30: 1216–23.
15. Wolpin BM, Hezel AF, Abrams T et al. Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J Clin Oncol 2009; 27: 193–8.
16. Royal RE, Levy C, Turner K et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother 2010; 33: 828–33.
17. Wolpin BM, O’Reilly EM, Ko YJ et al. Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer. Ann Oncol 2013; 24: 1792–801.
18. Grubbs SS, Grusenmeyer PA, Petrelli NJ, Gralla RJ. Is it cost-effective to add erlotinib to gemcitabine in advanced pancreatic cancer? J Clin Oncol 2006; 24 (18S): 6048.
19. Conroy T, Desseigne F, Ychou M et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364 (19): 1817–25.
20. Marsh Rde W, Talamonti MS, Katz MH, Herman JM. Pancreatic cancer and FOLFIRINOX: a new era and new questions. Cancer Med 2015; 4 (6): 853–63.
21. Desai N, Trieu V et al. Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res 2006; 12: 1317–24.
22. Von Hoff, D, Ramanathan R, Borad M et al. Gemcitabine Plus nab-Paclitaxel Is an Active Regimen in Patients With Advanced Pancreatic Cancer: A Phase I/II Trial. J Clin Oncol 2011; 36: 5742.
23. Von Hoff DD, Ramanathan R, Borad M et al. SPARC correlation with response to gemcitabine (G) plus nab-paclitaxel (nab-P) in patients with advanced metastatic pancreatic cancer: A phase I/II study. J Clin Oncol 2009; 27 (Suppl.): 4525.
24. Von Hoff DD, Ervin T, Arena FP et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369 (18): 1691–703.
25. Goldstein D, El-Maraghi RH, Hammel P et al. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. J Natl Cancer Inst 2015; 107 (2).
2. Burris AH, Moore MJ, Andersen J et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997; 15: 2403–13.
3. Berlin JD, Catalano P, Thomas JP et al. Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 2002; 20: 3270–5.
4. Bernhard J, Dietrich D, Scheithauer W et al. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol 2008; 26: 3695–701.
5. Louvet C, Labianca R, Hammel P et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 2005; 23: 3509–16.
6. Colucci G, Labianca R, Di Costanzo F et al. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol 2010; 28: 1645–5.
7. Rocha Lima CM, Green MR, Rotche R et al. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol 2004; 22: 3776–83.
8. Oettle H, Richards D, Ramanathan RK et al. A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer. Ann Oncol 2005; 16: 1639–45.
9. Philip PA, Benedetti J, Corless CL et al. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol 2010; 28: 3605–10.
10. Kindler HL, Niedzwiecki D, Hollis D et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol 2010; 28: 3617–22.
11. Moore MJ, Goldstein D, Hamm J et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007; 25: 1960–6.
12. Rougier P, Riess H, Manges R et al. Randomised, placebo-controlled, double-blind, parallelgroup phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. Eur J Cancer 2013; 49: 2633–42.
13. Kindler HL, Richards DA, Garbo LE et al. A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer. Ann Oncol 2012; 23: 2834–42.
14. Bodoky G, Timcheva C, Spigel DR et al. A phase II open-label random-ized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy. Invest New Drugs 2012; 30: 1216–23.
15. Wolpin BM, Hezel AF, Abrams T et al. Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J Clin Oncol 2009; 27: 193–8.
16. Royal RE, Levy C, Turner K et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother 2010; 33: 828–33.
17. Wolpin BM, O’Reilly EM, Ko YJ et al. Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer. Ann Oncol 2013; 24: 1792–801.
18. Grubbs SS, Grusenmeyer PA, Petrelli NJ, Gralla RJ. Is it cost-effective to add erlotinib to gemcitabine in advanced pancreatic cancer? J Clin Oncol 2006; 24 (18S): 6048.
19. Conroy T, Desseigne F, Ychou M et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364 (19): 1817–25.
20. Marsh Rde W, Talamonti MS, Katz MH, Herman JM. Pancreatic cancer and FOLFIRINOX: a new era and new questions. Cancer Med 2015; 4 (6): 853–63.
21. Desai N, Trieu V et al. Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res 2006; 12: 1317–24.
22. Von Hoff, D, Ramanathan R, Borad M et al. Gemcitabine Plus nab-Paclitaxel Is an Active Regimen in Patients With Advanced Pancreatic Cancer: A Phase I/II Trial. J Clin Oncol 2011; 36: 5742.
23. Von Hoff DD, Ramanathan R, Borad M et al. SPARC correlation with response to gemcitabine (G) plus nab-paclitaxel (nab-P) in patients with advanced metastatic pancreatic cancer: A phase I/II study. J Clin Oncol 2009; 27 (Suppl.): 4525.
24. Von Hoff DD, Ervin T, Arena FP et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369 (18): 1691–703.
25. Goldstein D, El-Maraghi RH, Hammel P et al. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. J Natl Cancer Inst 2015; 107 (2).
________________________________________________
2. Burris AH, Moore MJ, Andersen J et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997; 15: 2403–13.
3. Berlin JD, Catalano P, Thomas JP et al. Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 2002; 20: 3270–5.
4. Bernhard J, Dietrich D, Scheithauer W et al. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol 2008; 26: 3695–701.
5. Louvet C, Labianca R, Hammel P et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 2005; 23: 3509–16.
6. Colucci G, Labianca R, Di Costanzo F et al. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol 2010; 28: 1645–5.
7. Rocha Lima CM, Green MR, Rotche R et al. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol 2004; 22: 3776–83.
8. Oettle H, Richards D, Ramanathan RK et al. A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer. Ann Oncol 2005; 16: 1639–45.
9. Philip PA, Benedetti J, Corless CL et al. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol 2010; 28: 3605–10.
10. Kindler HL, Niedzwiecki D, Hollis D et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol 2010; 28: 3617–22.
11. Moore MJ, Goldstein D, Hamm J et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007; 25: 1960–6.
12. Rougier P, Riess H, Manges R et al. Randomised, placebo-controlled, double-blind, parallelgroup phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. Eur J Cancer 2013; 49: 2633–42.
13. Kindler HL, Richards DA, Garbo LE et al. A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer. Ann Oncol 2012; 23: 2834–42.
14. Bodoky G, Timcheva C, Spigel DR et al. A phase II open-label random-ized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy. Invest New Drugs 2012; 30: 1216–23.
15. Wolpin BM, Hezel AF, Abrams T et al. Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J Clin Oncol 2009; 27: 193–8.
16. Royal RE, Levy C, Turner K et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother 2010; 33: 828–33.
17. Wolpin BM, O’Reilly EM, Ko YJ et al. Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer. Ann Oncol 2013; 24: 1792–801.
18. Grubbs SS, Grusenmeyer PA, Petrelli NJ, Gralla RJ. Is it cost-effective to add erlotinib to gemcitabine in advanced pancreatic cancer? J Clin Oncol 2006; 24 (18S): 6048.
19. Conroy T, Desseigne F, Ychou M et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364 (19): 1817–25.
20. Marsh Rde W, Talamonti MS, Katz MH, Herman JM. Pancreatic cancer and FOLFIRINOX: a new era and new questions. Cancer Med 2015; 4 (6): 853–63.
21. Desai N, Trieu V et al. Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res 2006; 12: 1317–24.
22. Von Hoff, D, Ramanathan R, Borad M et al. Gemcitabine Plus nab-Paclitaxel Is an Active Regimen in Patients With Advanced Pancreatic Cancer: A Phase I/II Trial. J Clin Oncol 2011; 36: 5742.
23. Von Hoff DD, Ramanathan R, Borad M et al. SPARC correlation with response to gemcitabine (G) plus nab-paclitaxel (nab-P) in patients with advanced metastatic pancreatic cancer: A phase I/II study. J Clin Oncol 2009; 27 (Suppl.): 4525.
24. Von Hoff DD, Ervin T, Arena FP et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369 (18): 1691–703.
25. Goldstein D, El-Maraghi RH, Hammel P et al. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. J Natl Cancer Inst 2015; 107 (2).
Авторы
И.А.Покатаев*, С.А.Тюляндин
ФГБУ Российский онкологический научный центр им. Н.Н.Блохина Минздрава России.
115478, Россия, Москва, Каширское ш., д. 23
*Pokia@mail.ru
N.N.Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*Pokia@mail.ru
ФГБУ Российский онкологический научный центр им. Н.Н.Блохина Минздрава России.
115478, Россия, Москва, Каширское ш., д. 23
*Pokia@mail.ru
________________________________________________
N.N.Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*Pokia@mail.ru
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