Метастатический рак молочной железы (мРМЖ) продолжает оставаться неизлечимым заболеванием, однако современные возможности лекарственной терапии, обеспечивающие неуклонное расширение арсенала активных цитостатиков и появление новых лечебных опций, позволяют длительно контролировать рост опухоли, переводя патологию в разряд хронических. Одной из таких новых опций стал наб-паклитаксел – нанодисперсный паклитаксел, стабилизированный альбумином. Такая инновационная лекарственная форма обеспечивает активный транспорт препарата через сосудистый эндотелий с созданием его высокой концентрации в ткани опухоли. Клинические исследования по сравнению наб-паклитаксела с традиционными таксанами (паклитакселом и доцетакселом) продемонстрировали высокую эффективность нового препарата как в широкой популяции пациенток, так и в отдельных подгруппах, включая антрациклин-предлеченных больных, случаи с агрессивным течением заболевания, поражением висцеральных органов, у пациенток более молодого возраста и др. Наб-паклитаксел оказался активен и у таксан-предлеченных больных, что позволяет рассматривать его в качестве кандидата для повторного назначения таксанов и дает еще одну линию терапии. При HER2+ мРМЖ наб-паклитаксел может эффективно и безопасно комбинироваться с трастузумабом. Кроме того, благодаря своей уникальной формуле препарат не вызывает реакций гиперчувствительности и отличается от традиционных таксанов удобством применения. Отсутствие необходимости в премедикации дексаметазоном позволяет назначать его при таких сопутствующих заболеваниях, как тяжелая артериальная гипертензия, сахарный диабет, язва желудка и двенадцатиперстной кишки и т.д. Высокая безопасность наб-паклитаксела была подтверждена, в том числе у пожилых пациенток.
Metastatic breast cancer (mBC) continues to be an incurable disease, but modern drug therapy, associated with the steady extension of the arsenal of active cytostatic drugs and the development of new treatment options, provides the long-term control of tumor growth, transforming into chronic pathology. Nab-paclitaxel (nanodispersed albumin-bound paclitaxel) is one of such options. This innovative dosage form provides the active transport of the drug through the vascular endothelium with the creation of the high concentration in the tumor tissue. Clinical trial of nab-paclitaxel compared with traditional taxanes (paclitaxel and docetaxel) have demonstrated high efficiency of a new drug both in the general population and in the selected subgroups of patients, including treated with anthracyclines, patients with invasive disease, damages of the visceral organs, younger patients and others. Nab-paclitaxel proved to act in patients treated with taxanes, the physician can use this drug one again and thus we have another line of therapy. Nab-paclitaxel can be effectively and safely combined with trastuzumab in patients with mBC associated with HER2+. In addition, the drug because of the unique formula does not cause hypersensitivity reactions and differs from traditional taxanes of the variant of application. No need for premedication with dexamethasone let us appoint the drug in patients with comorbid conditions: severe arterial hypertension, diabetes, gastric and duodenal ulcers and others. High safety of nab-paclitaxel was approved in elderly patients as well.
Key words: metastatic breast cancer, taxanes, nab-paclitaxel.
1. Saad E, Katz A, Machado K, Buyse M. Post-Progression Survival (PPS) and Overall Survival (OS) According to Treatment Type in Contemporary Phase III Trials in Advanced Breast Cancer (ABC). SABCS 2009; Abstr 5116.
2. Gennari A, Conte PF, Rosso R et al. Survival of metastatic breast carcinoma patients over a 20-year period. A retrospective analysis based on individual patient data from six consecutive studies. Cancer 2005; 104 (8): 1742–50.
3. Dawood SS et al. Is the proportion of patients with synchronous stage IV breast cancer surviving > 2 years increasing over time? ASCO 2013; abstr. 524; JCO 2013; V31 (15S; part I): 12s.
4. Dawood S, Broglio K, Gonzalez-Angulo AM et al. Trends in survival over the past two decades among white and black patients with newly diagnosed stage IV breast cancer. J Clin Oncol 2008; 26: 4891–8.
5. American Cancer Society Web site Cancer Facts & Figures, 2011. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-029771.pd...
6. Cardoso F. Guidelines for the treatment of metastatic breast cancer. Presented at: Advanced Breast Cancer Third International Consensus Conference; 5–7 November 2015. Lisbon, Portugal.
7. Jordan MA, Wilson F. Microtubules as a target foranti cancer drugs. Nat Rev Cancer 2004; 4: 253–65.
8. Giaccone G, Pinedo HM. Drug resistance. Oncologist 1996; 1: 82–7. http://breast-cancer-research.com/pubmed/10387972
9. Giai M, Biglia N, Sismondi P. Chemoresistance in breast tumors. Eur J Gynaecol Oncol 1991; 12: 359–73.
10. Sparreboom A, Danesi R, Ando Y et al. Pharmacogenomics of ABC transporters and its role in cancer chemotherapy. Drug Resist Updat 2003; 6: 71–84.
11. Dumontet C, Sikic BI. Mechanisms of action of and resistance to antitubulin agents: microtubule dynamics, drug transport, and cell death. J Clin Oncol 1999; 17: 1061–70.
12. Trock BJ, Leonessa F, Clarke R. Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. J Natl Cancer Inst 1997; 89: 917–31.
13. Mechetner E, Kyshtoobayeva A, Zonis S et al. Levels of multidrugresistance (MDR1) P-glycoproteinexpression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin. Clin Cancer Res 1998; 4: 389–98.
14. Scheff RJ. Breast cancer and the new taxanes: focus on nab-paclitaxel. Commun Oncol 2008; 5 (Suppl. 8): 7–13.
15. Gardner ER, Dahut WL, Scripture CD et al. Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Clin Cancer Res 2008; 14 (13): 4200–5.
16. Hamad&Moghimi. Critical issues in site-specific targeting of solid tumours: the carrier, the tumour barriers and the bioavailable drug. Expert Opin Drug Deliv 2008; 5: 205–19.
17. Ten Tije AJ, Verweij J, Loos WJ, Sparreboom A. Pharmacological effects of formulation vehicles: Implications for cancer chemotherapy. Clin Pharmacokin 2003; 42: 665–8.
18. Chen N, Brachmann C, Liu X et al. Albumin-bound nanoparticle (nab) paclitaxel exhibits enhanced paclitaxel tissue distribution and tumor penetration. Cancer Chemother Pharmacol 2015; 76: 699–712.
19. Desai N, Trieu V, Yao Z 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 (4): 1317–24.
20. Desai NP, Trieu V, Hwang LY et al. Improved effectiveness of nanoparticle albumin-bound (nab) paclitaxel versus polysorbate-based docetaxel in multiple xenografts as a function of HER2 and SPARC status. Anti-cancer Drugs 2008; 19 (9): 899–909.
21. Hawkins M, Desai N, Soon-Shiong P. Rationale, preclinical support, and clinical proof-of-concept for formulating water-insoluble therapeutics as albumin-stabilized nanoparticles: experience with paclitaxel. Presented at AACR 2003; Poster 1189.
22. Scheff RJ. Breast cancer and the new taxanes: focus onnab-paclitaxel. Commun Oncol 2008; 5 (Suppl. 8): 7–13.
23. Ibrahim NK, Deasi N, Legha S et al. Phase I and pharmacokinetic study of ABI-007, a cremophor free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin Cancer Res 2002; 8 (5): 1038–44.
24. Gradishar WJ, Tjulandin S, Davidson N et al. Phase III trail of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol 2005; 23 (31): 7794–803.
25. Davidson N, Tjulandin S et al. Overall survival analysis of a randomized phase III trial compraing nab-paclitaxel with solvent-based paclitaxel in patients with metastatic breast cancer previously treated with anthracycline. Presented at the 6th European Breast Cancer Conference. 15–19 April, 2008; Berlin, Germany (Abstract 569).
26. FDA:http://www.accessdata.fda.gov/drugsatfda_docs/label/ 2012/021660s031lbl.pdf
27. Seidman A, Berry D, Cirrincione C et al. CALGB 9840: Phase III study of weekly (w) paclitaxel via 1-hour (h) infusion versus standard (S) 3 h infusion every third week in the treatment of metastatic breast cancer (MBC), with trastuzumab (T) forHER-2 positive metastatic breast cancer and randomized for TinHER-2 normal MBC. Proc ASCO 2004 (J Clin Oncol 2004); 22: 6s (abstr 512).
28. Gradishar WJ, Krasnojon D, Cheporov S et al. Phase II trial of nab-paclitaxel compared with docetaxel as first-line chemotherapy in patients with metastatic breast cancer: final analysis of overall survival. Clin Breast Cancer Res 2012; 12 (5): 313–21.
29. O'Shaughnessy J, Gradishar WJ, Bhar P, Iglesias J. Nab-paclitaxel for first-line treatment of patients with metastatic breast cancer and poor prognostic factors: a retrospective analysis. Breast Cancer Res 2013; 138: 829–37.
30. Krell J. What is the evidence for rechallenging with anthracyclines or taxanes in metastatic breast cancer? A review of the data. JCO 2009 (ASCO 2009); abstr. 1072.
31. Blum JL et al. Phase II Study of Weekly Albumin-Bound Paclitaxel for Patients with Metastatic Breast Cancer Heavily Pretreated with Taxanes Clin. Breast Cancer 2007; 7 (11): 850–6.
32. Palumbo R, Sottotetti F et al. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer patients: prospective evaluation of activity, safety, and quality of life. Drug Des Devel Ther 2015; 9: 2189–99.
33. Palumbo R, Sottotetti F et al. Targeted chemotherapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in metastatic breast cancer: which benefit for which patients? Ther Adv Med Oncol 2016; 8 (3): 209–29.
34. Fabi A et al. Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer: clinical results and biological observations in taxanepretreated patients. Drug Des Devel Ther 2015: 9; 6177–83.
35. Slamon DJ, Leyland-Jones B, Shak S et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 334: 783–92.
36. Keefe DL. Trastuzumab-associated cardiotoxicity. Cancer 2002; 95: 1592–600.
37. Seidman A, Hudis C, Pierri MK et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 2002; 20 (5): 1215–21.
38. Cortazar P, Johnson JR, Justice R, Pazdur R. Metastatic breast cancer (MBC): FDA approval overview. Proc ASCO 2008 (J Clin Oncol 2008); 26 (15S): Abstr. 1013.
39. Peacock NW, Infante JR, Yardley DA et al. Phase II trial of weekly docetaxel, vinorelbine and trastuzumab in the first-line treatment of patients (pts) with HER-2-positive metastatic breast cancer (MBC). Proc. ASCO 2008 (J Clin Oncol 2008); 26 (49S): Abstr. 1032.
40. Kash J, Barlow WE, Albain KS et al. Phase II Southwest Oncology Group study of docetaxel and vinorelbine plus filgrastim with weekly trastuzumab for HER-2-positive stage IV breast cancer. Proc. ASCO 2008 (J Clin Oncol 2008); 26 (49S): Abstr. 1033.
41. Mustacchi G, Biganzoli L, Pronzato P et al. HER2-positive metastatic breast cancer: a changing scenario. Crit Rev Oncol Hematol 2015; 95: 78–87.
42. Mirtsching B, Cosgriff T, Harker G et al. A phase II study ofweekly nanoparticle albumin-bound paclitaxel with orwithout trastuzumab in metastatic breast cancer. Clin Breast Cancer 2011; 11: 121–8.
43. Conlin A, Seidman A, Bach A et al. Phase II trial of weekly nanoparticle albumin-bound paclitaxel with carboplatin and trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer. Clin Breast Cancer 2010; 10: 281–7.
44. Desai et al. SABCS. 2004; Abstract 1071.
45. Kratz F. Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J Control Release. 2008; 132 (3): 171–83.
46. Peters TJr. Serum Albumin. Adv Protein Chem 1985; 37: 161–245.
47. Desai N. NabTM technology: a drug delivery platform utilising endothelial gp60 receptor-based transport and tumour-derived SPARC for targeting. Drug Delivery Report. 2007/2008; 16th Edition: 37–41.
48. Paal K et al. High affinity binding of paclitaxel to human serum albumin. Eur J Biochem 2001; 268 (7): 2187–91.
49. Elsadek B, Kratz F. Impact of albumin on drug delivery – new applications on the horizon. J Control Release 2012; 157 (1): 4–28.
________________________________________________
1. Saad E, Katz A, Machado K, Buyse M. Post-Progression Survival (PPS) and Overall Survival (OS) According to Treatment Type in Contemporary Phase III Trials in Advanced Breast Cancer (ABC). SABCS 2009; Abstr 5116.
2. Gennari A, Conte PF, Rosso R et al. Survival of metastatic breast carcinoma patients over a 20-year period. A retrospective analysis based on individual patient data from six consecutive studies. Cancer 2005; 104 (8): 1742–50.
3. Dawood SS et al. Is the proportion of patients with synchronous stage IV breast cancer surviving > 2 years increasing over time? ASCO 2013; abstr. 524; JCO 2013; V31 (15S; part I): 12s.
4. Dawood S, Broglio K, Gonzalez-Angulo AM et al. Trends in survival over the past two decades among white and black patients with newly diagnosed stage IV breast cancer. J Clin Oncol 2008; 26: 4891–8.
5. American Cancer Society Web site Cancer Facts & Figures, 2011. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-029771.pd...
6. Cardoso F. Guidelines for the treatment of metastatic breast cancer. Presented at: Advanced Breast Cancer Third International Consensus Conference; 5–7 November 2015. Lisbon, Portugal.
7. Jordan MA, Wilson F. Microtubules as a target foranti cancer drugs. Nat Rev Cancer 2004; 4: 253–65.
8. Giaccone G, Pinedo HM. Drug resistance. Oncologist 1996; 1: 82–7. http://breast-cancer-research.com/pubmed/10387972
9. Giai M, Biglia N, Sismondi P. Chemoresistance in breast tumors. Eur J Gynaecol Oncol 1991; 12: 359–73.
10. Sparreboom A, Danesi R, Ando Y et al. Pharmacogenomics of ABC transporters and its role in cancer chemotherapy. Drug Resist Updat 2003; 6: 71–84.
11. Dumontet C, Sikic BI. Mechanisms of action of and resistance to antitubulin agents: microtubule dynamics, drug transport, and cell death. J Clin Oncol 1999; 17: 1061–70.
12. Trock BJ, Leonessa F, Clarke R. Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. J Natl Cancer Inst 1997; 89: 917–31.
13. Mechetner E, Kyshtoobayeva A, Zonis S et al. Levels of multidrugresistance (MDR1) P-glycoproteinexpression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin. Clin Cancer Res 1998; 4: 389–98.
14. Scheff RJ. Breast cancer and the new taxanes: focus on nab-paclitaxel. Commun Oncol 2008; 5 (Suppl. 8): 7–13.
15. Gardner ER, Dahut WL, Scripture CD et al. Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Clin Cancer Res 2008; 14 (13): 4200–5.
16. Hamad&Moghimi. Critical issues in site-specific targeting of solid tumours: the carrier, the tumour barriers and the bioavailable drug. Expert Opin Drug Deliv 2008; 5: 205–19.
17. Ten Tije AJ, Verweij J, Loos WJ, Sparreboom A. Pharmacological effects of formulation vehicles: Implications for cancer chemotherapy. Clin Pharmacokin 2003; 42: 665–8.
18. Chen N, Brachmann C, Liu X et al. Albumin-bound nanoparticle (nab) paclitaxel exhibits enhanced paclitaxel tissue distribution and tumor penetration. Cancer Chemother Pharmacol 2015; 76: 699–712.
19. Desai N, Trieu V, Yao Z 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 (4): 1317–24.
20. Desai NP, Trieu V, Hwang LY et al. Improved effectiveness of nanoparticle albumin-bound (nab) paclitaxel versus polysorbate-based docetaxel in multiple xenografts as a function of HER2 and SPARC status. Anti-cancer Drugs 2008; 19 (9): 899–909.
21. Hawkins M, Desai N, Soon-Shiong P. Rationale, preclinical support, and clinical proof-of-concept for formulating water-insoluble therapeutics as albumin-stabilized nanoparticles: experience with paclitaxel. Presented at AACR 2003; Poster 1189.
22. Scheff RJ. Breast cancer and the new taxanes: focus onnab-paclitaxel. Commun Oncol 2008; 5 (Suppl. 8): 7–13.
23. Ibrahim NK, Deasi N, Legha S et al. Phase I and pharmacokinetic study of ABI-007, a cremophor free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin Cancer Res 2002; 8 (5): 1038–44.
24. Gradishar WJ, Tjulandin S, Davidson N et al. Phase III trail of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol 2005; 23 (31): 7794–803.
25. Davidson N, Tjulandin S et al. Overall survival analysis of a randomized phase III trial compraing nab-paclitaxel with solvent-based paclitaxel in patients with metastatic breast cancer previously treated with anthracycline. Presented at the 6th European Breast Cancer Conference. 15–19 April, 2008; Berlin, Germany (Abstract 569).
26. FDA:http://www.accessdata.fda.gov/drugsatfda_docs/label/ 2012/021660s031lbl.pdf
27. Seidman A, Berry D, Cirrincione C et al. CALGB 9840: Phase III study of weekly (w) paclitaxel via 1-hour (h) infusion versus standard (S) 3 h infusion every third week in the treatment of metastatic breast cancer (MBC), with trastuzumab (T) forHER-2 positive metastatic breast cancer and randomized for TinHER-2 normal MBC. Proc ASCO 2004 (J Clin Oncol 2004); 22: 6s (abstr 512).
28. Gradishar WJ, Krasnojon D, Cheporov S et al. Phase II trial of nab-paclitaxel compared with docetaxel as first-line chemotherapy in patients with metastatic breast cancer: final analysis of overall survival. Clin Breast Cancer Res 2012; 12 (5): 313–21.
29. O'Shaughnessy J, Gradishar WJ, Bhar P, Iglesias J. Nab-paclitaxel for first-line treatment of patients with metastatic breast cancer and poor prognostic factors: a retrospective analysis. Breast Cancer Res 2013; 138: 829–37.
30. Krell J. What is the evidence for rechallenging with anthracyclines or taxanes in metastatic breast cancer? A review of the data. JCO 2009 (ASCO 2009); abstr. 1072.
31. Blum JL et al. Phase II Study of Weekly Albumin-Bound Paclitaxel for Patients with Metastatic Breast Cancer Heavily Pretreated with Taxanes Clin. Breast Cancer 2007; 7 (11): 850–6.
32. Palumbo R, Sottotetti F et al. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer patients: prospective evaluation of activity, safety, and quality of life. Drug Des Devel Ther 2015; 9: 2189–99.
33. Palumbo R, Sottotetti F et al. Targeted chemotherapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in metastatic breast cancer: which benefit for which patients? Ther Adv Med Oncol 2016; 8 (3): 209–29.
34. Fabi A et al. Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer: clinical results and biological observations in taxanepretreated patients. Drug Des Devel Ther 2015: 9; 6177–83.
35. Slamon DJ, Leyland-Jones B, Shak S et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 334: 783–92.
36. Keefe DL. Trastuzumab-associated cardiotoxicity. Cancer 2002; 95: 1592–600.
37. Seidman A, Hudis C, Pierri MK et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 2002; 20 (5): 1215–21.
38. Cortazar P, Johnson JR, Justice R, Pazdur R. Metastatic breast cancer (MBC): FDA approval overview. Proc ASCO 2008 (J Clin Oncol 2008); 26 (15S): Abstr. 1013.
39. Peacock NW, Infante JR, Yardley DA et al. Phase II trial of weekly docetaxel, vinorelbine and trastuzumab in the first-line treatment of patients (pts) with HER-2-positive metastatic breast cancer (MBC). Proc. ASCO 2008 (J Clin Oncol 2008); 26 (49S): Abstr. 1032.
40. Kash J, Barlow WE, Albain KS et al. Phase II Southwest Oncology Group study of docetaxel and vinorelbine plus filgrastim with weekly trastuzumab for HER-2-positive stage IV breast cancer. Proc. ASCO 2008 (J Clin Oncol 2008); 26 (49S): Abstr. 1033.
41. Mustacchi G, Biganzoli L, Pronzato P et al. HER2-positive metastatic breast cancer: a changing scenario. Crit Rev Oncol Hematol 2015; 95: 78–87.
42. Mirtsching B, Cosgriff T, Harker G et al. A phase II study ofweekly nanoparticle albumin-bound paclitaxel with orwithout trastuzumab in metastatic breast cancer. Clin Breast Cancer 2011; 11: 121–8.
43. Conlin A, Seidman A, Bach A et al. Phase II trial of weekly nanoparticle albumin-bound paclitaxel with carboplatin and trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer. Clin Breast Cancer 2010; 10: 281–7.
44. Desai et al. SABCS. 2004; Abstract 1071.
45. Kratz F. Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J Control Release. 2008; 132 (3): 171–83.
46. Peters TJr. Serum Albumin. Adv Protein Chem 1985; 37: 161–245.
47. Desai N. NabTM technology: a drug delivery platform utilising endothelial gp60 receptor-based transport and tumour-derived SPARC for targeting. Drug Delivery Report. 2007/2008; 16th Edition: 37–41.
48. Paal K et al. High affinity binding of paclitaxel to human serum albumin. Eur J Biochem 2001; 268 (7): 2187–91.
49. Elsadek B, Kratz F. Impact of albumin on drug delivery – new applications on the horizon. J Control Release 2012; 157 (1): 4–28.
Авторы
Е.В.Артамонова*
ФГБУ «Российский онкологический научный центр им. Н.Н.Блохина» Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*artamonovae@mail.ru
________________________________________________
E.V.Artamonova*
N.N.Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*artamonovae@mail.ru