Kombinace systematických terapií s radiací u nemalobuněčného karcinomu plic

Radioterapie je hlavní léčebnou modalitou při léčbě III. stadia nemalobuněčného plicního karcinomu. Na počátku 90. let 20. století byla zavedena kombinovaná léčba s chemoterapií. V roce 1995 prokázala metaanalýza zlepšené výsledky léčby při sekvenčním použití chemoterapie a radioterapie založené na cisplatině v porovnání se samotnou radioterapií. Následné randomizované studie a dvě metaanalýzy prokázaly, že současně používaná radiochemoterapie převyšuje sekvenční používání obou metod v celkovém přežití i lokální kontrole onemocnění. Přesto zůstává v rámci výsledků léčby a profilu toxicity nezodpovězeno několik otázek, včetně optimálního režimu chemoterapie a dávky a techniky radioterapie. Cílená léčba představuje novou třídu léčiv, která reagují se specifickými molekulárními cíli (typicky proteiny), které hrají klíčovou roli v růstu nádoru a progresi. Některé kombinace se jeví jako příliš toxické, jako třeba protilátka proti vaskulárnímu epiteliálnímu růstovému faktoru – bevacizumab. Možnost přidání inhibitoru receptoru epidermálního růstového inhibičního faktoru cetuximabu byla nedávno popsána u pacientů s nemalobuněčným karcinomem plic. Jsou zapotřebí vyvinout strategie, jak bezpečně začlenit nová antiangiogenní agens do kombinované terapie u rakoviny plic. Rychlý rozvoj molekulární onkologie snad přispěje k lepšímu výběru pacientů pro jednotlivé strategie a k optimalizaci léčby. K dalšímu zlepšení výsledků léčby může dále vést zvýšení dávek radioterapie, aplikované v souladu s nejnovějšími technikami a v kombinaci s novými biologickými látkami.

Klíčová slova:
karcinom plic – chemoterapie – radioterapie – farmakoterapie

Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy.

Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů.

Obdrženo:
27. 7. 2015

Přijato:
14. 9. 2015

Autoři: K. Adamowicz; E. Goszczynska‑ matysiak
Působiště autorů: Department of Oncology, Regional Oncology Center of Gdansk, Poland
Vyšlo v časopise: Klin Onkol 2015; 28(5): 321-331
Kategorie: Přehledy
prolekare.web.journal.doi_sk: https://doi.org/10.14735/amko2015321

Souhrn

Obdrženo:
27. 7. 2015

Přijato:
14. 9. 2015

Zdroje

1. Ferlay J, Shin HR, Bray F et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127(12): 2893– 2917. doi: 10.1002/ ijc.25516.

2. Jemal A, Siegel R, Ward E et al. Cancer Statistics, 2007. CA Cancer J Clin 2007; 57(1): 43– 66.

3. Perez CA, Stanley K, Grundy G et al. Impact of irradiation technique and tumor extent in tumor control and survival of patients with unresectable non‑oat cell carcinoma of the lung: report by the Radiation Therapy Oncology Group. Cancer 1982; 50(6): 1091– 1099.

4. Saunders MI, Dische S. Continuous, hyperfractionated, accelerated radiotherapy (CHART) in non‑small cell carcinoma of the bronchus. Int J Radiat Oncol Biol Phys 1990; 19(5): 1211– 1215.

5. Kong FM, Ten Haken RK, Schipper MJ et al. High‑dose radiation improved local tumor control and overall survival in patients with inoperable/ unresectable non‑small-‑cell lung cancer: long‑term results of a radiation dose escalation study. Int J Radiat Oncol Biol Phys 2005; 63(2): 324– 333.

6. Wurstbauer K, Weise H, Deutschmann H et al. Non‑ small cell lung cancer in stages I– IIIB: Long‑term results of definitive radiotherapy with doses ≥ 80 Gy in standard fractionation. Strahlenther Onkol 2010; 186(10): 551– 557. doi: 10.1007/ s00066‑ 010‑ 2108‑ 3.

7. Machtay M, Bae K, Movsas B et al. Higher biologically effective dose of radiotherapy is associated with improved outcomes for locally advanced non‑small cell lung carcinoma treated with chemoradiation: an analysis of the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 2012; 82(1): 425– 434. doi: 10.1016/ j.ijrobp.2010.09.004.

8. Guckenberger M, Wilbert J, Richter A et al. Potential of adaptive radiotherapy to escalate the radiation dose in combined radiochemotherapy for locally advanced non‑small cell lung cancer. Int J Radiat Oncol Biol Phys 2011; 79(3): 901– 908. doi: 10.1016/ j.ijrobp.2010.04.050.

9. De Ruysscher D, Faivre‑Finn C, Nestle U et al. European Organization for Research and Treatment of Cancer recommendations for planning and delivery of high‑dose, high‑precision radiotherapy for lung cancer. J Clin Oncol 2010; 28(36): 5301– 5310. doi: 10.1200/ JCO.2010.30.3271.

10. Dillman RO, Seagren SL, Propert KJ et al. A randomized trial of induction chemotherapy plus high‑dose radiation versus radiation alone in stage III non‑small‑cell lung cancer. N Engl J Med 1990; 323(14): 940– 945.

11. Collaborative Group. Chemotherapy in non‑smallcell lung cancer: a meta‑analysis using updated data on individual patients from 52 randomized clinical trials. BMJ 1995; 311(7010): 899– 909.

12. Le Chevalier T, Arriagada R, Quoix E et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non‑small‑cell lung cancer: first analysis of a randomized trial in 353 patients. J Natl Cancer Inst 1991; 83(6): 417– 423.

13. Jassem J, Begg AC, Stewart F et al. Combined chemotherapy and radiotherapy In: Peckham M, Pinedo HM, Veronesi U (eds). Oxford textbook of oncology. Oxford: Oxford University Press 1995: 811– 823.

14. Schaake‑ Koning C, Van den Bogaert W, Dalesio O et al. Effects of concomitant cisplatin and radiotherapy on inoperable non‑small‑cell lung cancer. N Engl J Med 1992; 326(8): 524– 530.

15. Trovo MG, Minatel E, Franchin G et al. Radiotherapy versus radiotherapy enhanced by cisplatin in stage III non‑small cell lung cancer. Int J Radiat Oncol Biol Phys 1992; 24(7): 11– 15.

16. Aupérin A, Le Péchoux C, Pignon JP et al. Concomitant radio‑ chemotherapy based on platin compounds in patients with locally advanced non‑small cell lung cancer (NSCLC): a meta‑analysis of individual data from 1,764 patients. Ann Oncol 2006; 17(3): 473– 483.

17. Rowell NP, O’rourke NP. Concurrent chemoradiotherapy in non‑small cell lung cancer. Cochrane Database Syst Rev 2004; (4): CD002140.

18. Clamon G, Herndon J, Eaton W et al. A feasibility study of extended chemotherapy for locally advanced non‑small cell lung cancer: a phase II trial of cancer and leukemia group B. Cancer Invest 1994; 12(3): 273– 282.

19. Fournel P, Robinet G, Thomas P et al. Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non‑small‑cell lung cancer: groupe Lyon‑ Saint‑ Etienne d’Oncologie Thoracique‑ Groupe Français de Pneumo‑ Cancérologie NPC 95– 01 Study. J Clin Oncol 2005; 23(25): 5910– 5917.

20. Furuse K, Fukuoka M, Kawahara M et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non‑small‑cell lung cancer. J Clin Oncol 1999; 17(9): 2692– 2699.

21. Ulutin HC, Güden M, Oysul K et al. Split‑ course radiotherapy with or without concurrent or sequential chemotherapy in non‑small cell lung cancer. Radiat Med 2000; 18(2): 93– 96.

22. Zatloukal P, Petruzelka L, Zemanova M et al. Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non‑small cell lung cancer: a randomized study. Lung Cancer 2004; 46(1): 87– 98.

23. Belderbos J, Uitterhoeve L, van Zandwijk N et al. Randomized trial of sequential versus concurrent chemo‑ radiotherapy in patients with inoperable non‑small cell lung cancer (EORTC 08972– 22973). Eur J Cancer 2007; 43(1): 114– 121.

24. Aupérin A, Le Péchoux C, Rolland E et al. Meta‑analysis of concomitant versus sequential radiochemotherapy in locally advanced non‑small‑cell lung cancer. J Clin Oncol 2010; 28(13): 2181– 2190. doi: 10.1200/ JCO.2009.26.2543.

25. O‘Rourke N, Roqué I Figuls M, Farré Bernadó N et al. Concurrent chemoradiotherapy in non‑small cell lung cancer. Cochrane Database Syst Rev 2010; 6: CD002140. doi: 10.1002/ 14651858.CD002140.pub3.

26. Auperin A, Rolland E, Curran W Jr et al. Concomitant radio‑ chemotherapy (RT‑ CT) versus sequential RT‑ CT in locally advanced non‑small cell lung cancer (NSCLC): a meta‑analysis using individual patient data (IPD) from randomized clinical trials (RCTs). J Thorac Oncol 2007; 2 (Suppl 4): S310.

27. Robinson LA, Ruckdeschel JC, Wagner H Jr et al. Treatment of non‑small cell lung cancer‑stage IIIA: ACCP evidence‑based clinical practice guidelines (2nd ed.). Chest 2007; 132 (Suppl 3): 243S– 265S.

28. Jett JR, Schild SE, Keith RL et al. Treatment of non‑smallcell lung cancer, stage IIIB: ACCP evidence‑based clinical practice guidelines (2nd ed). Chest 2007; 132 (Suppl 3): 266S– 276S.

29. Mayor S. NICE issues guidance for diagnosis and treatment of lung cancer. BMJ 2005; 330(7489): 439.

30. De Ruysscher D, Botterweck A, Dirx M et al. Eligibility for concurrent chemotherapy and radiotherapy of locally advanced lung cancer patients: a prospective, population‑based study. Ann Oncol 2009; 20(1): 98– 102. doi: 10.1093/ annonc/ mdn559.

31. El Sharouni SY, Kal HB, Battermann JJ. Accelerated regrowth of non‑small‑cell lung tumours after induction chemotherapy. Br J Cancer 2003; 89(12): 2184– 2189.

32. Chen CP, Weinberg VK, Jahan TM et al. Implications of delayed initiation of radiotherapy: accelerated repopulation after induction chemotherapy for stage III non‑smallcell lung cancer. J Thorac Oncol 2011; 6(11): 1857– 1864. doi: 10.1097/ JTO.0b013e318229a41e.

33. Machtay M, Hsu C, Komaki R et al. Effect of overalltreatment time on outcomes after concurrent chemoradiation for locally advanced non‑small‑cell lung carcinoma: analysis of the Radiation Therapy Oncology Group (RTOG) experience. Int J Radiat Oncol Biol Phys 2005; 63(3): 667– 671.

34. Hanna NN, Seetharam S, Mauceri HJ et al. Antitumor interaction of short‑ course endostatin and ionizing radiation. Cancer J 2000; 6(5): 287– 293.

35. Dings RP, Williams BW, Song CW et al. Anginex synergizes with radiation therapy to inhibit tumor growth by radiosensitizing endothelial cells. Int J Cancer 2005; 115(2): 312– 319.

36. Citrin D, Menard C, Camphausen K. Combining radiotherapy and angiogenesis inhibitors: clinical trial design. Int J Radiat Oncol Biol Phys 2006; 64(1): 15– 25.

37. Fogarty M. Learning from angiogenesis trial failures. The Scientist 2002; 16: 33– 35.

38. Gorski DH, Beckett MA, Jaskowiak NT et al. Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res 1999; 59(14): 3374– 3378.

39. Abdollahi A, Lipson KE, Sckell A et al. Combined therapy with direct and indirect angiogenesis inhibition results in enhanced antiangiogenic and antitumor effects. Cancer Res 2003; 63(24): 8890– 8898.

40. Winkler F, Kozin SV, Tong RT et al. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin‑1, and matrix metalloproteinases. Cancer Cell 2004; 6(6): 553– 563.

41. Spigel DR, Hainsworth JD, Yardley DA et al. Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab. J Clin Oncol 2010; 28(1): 43– 48. doi: 10.1200/ JCO.2009.24.7353.

42. Socinski MA, Stinchcombe TE, Moore DT et al. Incorporating bevacizumab and erlotinib in the combined‑ modality treatment of stage III non‑small‑cell lung cancer: results of a phase I/ II trial. J Clin Oncol 2012; 30(32): 3953– 3959. doi: 10.1200/ JCO.2012.41.9820.

43. Tanaka T, Munshi A, Brooks C et al. Gefitinib radiosensitizes non‑small cell lung cancer cells by suppressing cellular DNA repair capacity. Clin Cancer Res 2008; 14(4): 1266– 1273. doi: 10.1158/ 1078‑ 0432.CCR‑ 07‑ 1606.

44. Kelly K, Chansky K, Gaspar LE et al. Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non‑small‑cell lung cancer: SWOG S0023. J Clin Oncol 2008; 26(15): 2450– 2456. doi: 10.1200/ JCO.2007.14.4824.

45. Shepherd FA, Rodrigues Pereira J, Ciuleanu T et al. Erlotinib in previously treated non‑small‑cell lung cancer. N Engl J Med 2005; 353(2): 123– 132.

46. Zhu CQ, da Cunha Santos G, Ding K et al. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2008; 26(26): 4268– 4275. doi: 10.1200/ JCO.2007.14.8924.

47. Kim JC, Ali MA, Nandi A et al. Correlation of HER1/ EGFR expression and degree of radiosensitizing effect of the HER1/ EGFR‑ tyrosine kinase inhibitor erlotinib. Indian J Biochem Biophys 2005; 42(6): 358– 365.

48. Chinnaiyan P, Huang S, Vallabhaneni G et al. Mechanisms of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva). Cancer Res 2005; 65(8): 3328– 3335.

49. Nyati MK, Morgan MA, Feng FY et al. Integration of EGFR inhibitors with radiochemotherapy. Nat Rev Cancer 2006; 6(11): 876– 885.

50. Baumann M, Krause M, Dikomey E et al. EGFR‑ targeted anti‑cancer drugs in radiotherapy: preclinical evaluation of mechanisms. Radiother Oncol 2007; 83(3): 238– 248.

51. Tortora G, Gelardi T, Ciardiello F et al. The rationale for the combination of selective EGFR inhibitors with cytotoxic drugs and radiotherapy. Int J Biol Markers 2007; 22 (Suppl 4): S47– S52.

52. Martinez E, Martinez M, Viñolas N et al. Feasibility and tolerability of the addition of erlotinib to 3D thoracic radiotherapy (RT) in patients (p) with unresectable NSCLC: a prospective randomized phase II study. J Clin Oncol 2008; 26: abstr. 7563.

53. Milas L, Fan Z, Andratschke NH et al. Epidermal growth factor receptor and tumor response to radiation: in vivo preclinical studies. Int J Radiat Oncol Biol Phys 2004; 58(3): 966– 971.

54. Nasu S, Ang KK, Fan Z et al. C225 antiepidermal growth factor receptor antibody enhances tumor radiocurability. Int J Radiat Oncol Biol Phys 2001; 51(2): 474– 477.

55. Govindan R, Bogart J, Stinchcombe T et al. Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non‑small‑cell lung cancer: Cancer and Leukemia Group B trial 30407. J Clin Oncol 2011; 29(23): 3120– 3125. doi: 10.1200/ JCO.2010.33.4979.

56. Jatoi A, Schild SE, Foster N et al. A phase II study of cetuximab and radiation in elderly and/ or poor performance status patients with locally advanced non‑small-‑cell lung cancer (N0422) Ann Oncol 2010; 21(10): 2040– 2044. doi: 10.1093/ annonc/ mdq075.

57. Jensen AD, Münter MW, Bischoff HG et al. Combined treatment of nonsmall cell lung cancer stage III with intensity‑ modulated radiotherapy and cetuximab: the NEAR trial. Cancer 2011; 117(13): 2986– 2994. doi: 10.1002/ cncr.25888.

58. Hallqvist A, Wagenius G, Rylander H et al. Concurrent cetuximab and radiotherapy after docetaxel‑cisplatin induction chemotherapy in stage III NSCLC: satellite – a phase II study from the Swedish Lung Cancer Study Group. Lung Cancer 2011; 71(2): 166– 172. doi: 10.1016/ j.lungcan.2010.05.011.

59. Hughes S, Liong J, Miah A et al. A brief report on the safety study of induction chemotherapy followed by synchronous radiotherapy and cetuximab in stage III non‑small cell lung cancer (NSCLC): SCRATCH study. J Thorac Oncol 2008; 3(6): 648– 651. doi: 10.1097/ JTO.0b013e3181757a60.

60. Blumenschein GR Jr, Paulus R, Curran WJ et al. Phase IIstudy of cetuximab in combination with chemoradiation in patients with stage IIIA/ B non‑small‑cell lung cancer: RTOG 0324. J Clin Oncol 2011; 29(17): 2312– 2318. doi: 10.1200/ JCO.2010.31.7875.

61. Govindan R, Bogart J, Stinchcombe T et al. Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non‑small‑cell lung cancer: Cancer and Leukemia Group B Trial 30407. J Clin Oncol 2011; 29(23): 3120– 3125. doi: 10.1200/ JCO.2010.33.4979.

62. Noordijk EM, Poest Clement E et al. Radiotherapy as an alternative to surgery in elderly patients with resectable lung cancer. Radiother Oncol 1988; 13(2): 83– 89.

63. Onishi H, Shirato H, Nagata Y et al. Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage Inon‑small cell lung cancer: updated results of 257 patients in a Japanese multi‑institutional study. J Thorac Oncol 2007; 2 (Suppl 3): 94– 100.

64. Sibley GS. Radiotherapy for patients with medically inoperablestage I nonsmall cell lung carcinoma: smaller volumes and higherdoses – a review. Cancer 1998; 82(3): 433– 438.

65. Timmerman R, Paulus R, Galvin J et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 2010; 303(11): 1070– 1076. doi: 10.1001/ jama.2010.261.

66. Grills IS, Yan D, Martinez AA et al. Potential for reduced toxicity and dose escalation in the treatment of inoper-able non‑small‑cell lung cancer: a comparison of intensity‑ modulated radiation therapy (IMRT), 3D conformal radiation, and elective nodal irradiation. Int J Radiat Oncol Biol Phys 2003; 57(3): 875– 890.

67. Murshed H, Liu HH, Liao Z et al. Dose and volume reduction for normal lung using intensity‑ modulated radiotherapy for advanced‑stage non‑small‑cell lung cancer. Int J Radiat Oncol Biol Phys 2004; 58(4): 1258– 1267.

68. Schwarz M, Alber M, Lebesque JV et al. Dose heterogeneity in the target volume and intensity‑ modulated radiotherapy to escalate the dose in the treatment of non‑small‑cell lung cancer. Int J Radiat Oncol Biol Phys 2005; 62(2): 561– 570.

69. Park C, Papiez L, Zhang S et al. Universal survival curve and single fraction equivalent dose: useful tools in understanding potency of ablative radiotherapy. Int J Radiat Oncol Biol Phys 2008; 70(3): 847– 852. doi: 10.1016/ j.ijrobp.2007.10.059.

70. Bradley JD, Paulus R, Komaki R et al. A randomized phase III comparison of standard‑dose (60 Gy) versus high‑dose (74 Gy) conformal chemoradiotherapy with or without cetuximab for stage IIIa/ IIIb non‑small cell lung cancer: preliminary findings on radiation dose in RTOG 0617. 53rd Annual Meeting of the American Society of Radiation Oncology; Miami, FL, USA. 2– 6 October 2011.

71. Janssen‑ Heijnen ML, Smulders S, Lemmens VE et al. Effect of comorbidity on the treatment and prognosis of elderly patients with non‑small cell lung cancer. Thorax 2004; 59(7): 602– 607.

72. Pignon T, Gregor A, Schaake Koning C et al. Age has no impact on acute and late toxicity of curative thoracic radiotherapy. Radiother Oncol 1998; 46(3): 239– 248.

73. Socinski MA. Clinical issues in the management of non‑small‑cell lung cancer and the role of platinum‑based therapy. Clin Lung Cancer 2004; 5(5): 274– 289.

74. Takata I, Ueoka H, Kiura K et al. Daily low‑dose cisplatin and concurrent thoracic irradiation for poor‑ risk patients with unresectable non‑small‑cell lung cancer. Acta Med Okayama 2002; 56(5): 261– 266.

75. Uitterhoeve AL, Koolen MG, van Os RM et al. Accelerated high‑dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with non‑small cell lung cancer. Radiat Oncol 2007; 2(1): 27.

76. Bartelink H, Kallman RF, Rapacchietta D et al. Thera-peutic enhancement in mice by clinically relevant dose and fractionation schedules of cis‑diamminedichloropla-tinum (II) and irradiation. Radiother Oncol 1986; 6(1): 61– 74.