局部转移性晚期甲状腺癌分子靶向药物治疗
|
摘要
晚期碘难治性甲状腺癌(radioactive iodine-refractory DTC,RAIR DTC)、甲状腺未分化癌和晚期髓样癌目前仍缺少有效治疗方法,一旦发生局部复发或远处转移,严重威胁病人的生命。随着甲状腺癌分子生物学研究的蓬勃发展,许多有效的药物分子作用靶标相继被发现。基于一个或多个靶点研发出分子靶向药物已经完成或正在进行治疗甲状腺癌的临床试验,展现出良好的发展和应用前景。索拉非尼、凡德尼布、乐伐替尼以及卡博替尼已被美国食品药品监督管理局(FDA)批准用于进展期甲状腺癌的治疗;阿西替尼、司美替尼等分子靶向抑制剂已通过Ⅱ/Ⅲ期临床试验,这些药物的出现为晚期甲状腺癌以及进展期髓样癌的治疗提供了全新的选择。这些靶向药物具有特异性强、副反应较小、疗效好等优点,在甲状腺癌的治疗中具有广阔的前景。
There is still a lack of effective treatment for radioactive iodine-refractory DTC(RAIR DTC),anaplastic thyroid cancer(ATC)and medullary thyroid cancer(MTC).Once recurrence and metastasis occur,the patient's life is seriously threatened. With the vigorous development of molecular biology of thyroid cancer,many effective molecular targets have been found. Based on one or more targets,molecular targeted drugs underwent clinical trials for the treatment of thyroid cancer,showing good development and application prospects. Sorafenib,vandetanib,lenvatinib and cabozantinib have been approved by FDA for the treatment of advanced thyroid carcinoma. Other molecular targeting inhibitors,such as axitinib and selumetinib,have passed phaseⅡ/Ⅲ clinical trials. The emergence of the drugs provides new choices for the treatment of advanced thyroid cancer and advanced MTC. The drugs have many advantages,such as strong specificity,less side effects and good curative effect,having broad prospects in the treatment of thyroid cancer.
There is still a lack of effective treatment for radioactive iodine-refractory DTC(RAIR DTC),anaplastic thyroid cancer(ATC)and medullary thyroid cancer(MTC).Once recurrence and metastasis occur,the patient's life is seriously threatened. With the vigorous development of molecular biology of thyroid cancer,many effective molecular targets have been found. Based on one or more targets,molecular targeted drugs underwent clinical trials for the treatment of thyroid cancer,showing good development and application prospects. Sorafenib,vandetanib,lenvatinib and cabozantinib have been approved by FDA for the treatment of advanced thyroid carcinoma. Other molecular targeting inhibitors,such as axitinib and selumetinib,have passed phaseⅡ/Ⅲ clinical trials. The emergence of the drugs provides new choices for the treatment of advanced thyroid cancer and advanced MTC. The drugs have many advantages,such as strong specificity,less side effects and good curative effect,having broad prospects in the treatment of thyroid cancer.
引文
[1]王波,赵文新.甲状腺癌靶向治疗进展[J].中国实用外科杂志,2015,35(6):674-678.
[2]Ferrari SM,Politti U,Spisni R,et al.Sorafenib in the treatment of thyroid cancer[J].Expert Rev Anticancer Ther,2015,15(8):863-874.
[3]Brose MS,Nutting CM,Jarzab B,et al.Sorafenib in radioactive iodine-refractory,locally advanced or metastatic differentiated thyroid cancer:a randomised,double-blind,phase 3 trial[J].Lancet,2014,384(9940):319-328.
[4]Ito Y,Onoda N,Ito KI,et al.Sorafenib in Japanese patients with locally advanced or metastatic medullary thyroid carcinoma and anaplastic thyroid carcinoma[J].Thyroid,2017,27(9):1142-1148.
[5]Fallahi P,Di FB,Ferrari SM,et al.Selective use of vandetanib in the treatment of thyroid cancer[J].Drug Design Development AND Therapy,2015,9:3459-3470.
[6]Chougnet CN,Borget I,Leboulleux S,et al.Vandetanib for the treatment of advanced medullary thyroid cancer outside a clinical trial:results from a French cohort[J].Thyroid,2015,25(4):386-391.
[7]Uchino K,Komoda M,Tomomatsu J,et al.Safety and tolerability of vandetanib in Japanese patients with medullary thyroid cancer:A phase I/II open-label study[J].Endocr Pract,2017,23(2):149-156.
[8]Brose MS,Worden FP,Newbold KL,et al.Effect of age on the efficacy and safety of lenvatinib in radioiodine-refractory differentiated thyroid cancer in the phase III select trial[J].J Clin Oncol,2017,35(23):2692-2699.
[9]Robinson B,Schlumberger M,Wirth LJ,et al.Characterization of tumor size changes over time from the phase 3 study of lenvatinib in thyroid cancer[J].J Clin Endocrinol Metab,2016,101(11):4103-4109.
[10]Schlumberger M,Jarzab B,Cabanillas ME,et al.A phase II trial of the multitargeted tyrosine kinase inhibitor lenvatinib(E7080)in advanced medullary thyroid cancer[J].Clin Cancer Res,2012,22(1):44-53.
[11]Lorusso L,Newbold K.Lenvatinib:a new option for the treatment of advanced iodine refractory differentiated thyroid cancer?[J].Future Oncol,2015,11(12):1719-1727.
[12]Schlumberger M,Tahara M,Wirth LJ,et al.Lenvatinib versus placebo in radioiodine-refractory thyroid cancer[J].N Engl JMed,2015,372(7):621-630.
[13]I iguez-Ariza NM,Ryder MM,Hilger CR,et al.Salvage lenvatinib therapy in metastatic anaplastic thyroid cancer[J].Thyroid,2017,27(7):923-927.
[14]Krajewska J,Olczyk T,Jarzab B.Cabozantinib for the treatment of progressive metastatic medullary thyroid cancer[J].Expert Rev Clin Pharmacol,2016,9(1):69-79.
[15]Schlumberger M,Elisei R,Müller S,et al.Overall survival analysis of EXAM,a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma[J].Ann Oncol,2017,28(11):2813-2819.
[16]Belum VR,Serna-Tamayo C,Wu S,et al.Incidence and risk of hand-foot skin reaction with cabozantinib,a novel multikinase inhibitor:a meta-analysis[J].Clin Exp Dermatol,2016,41(1):8-15.n
[17]Cabanillas ME,de Souza JA,Geyer S,et al.Cabozantinib as salvage therapy for patients with tyrosine kinase inhibitor-refractory differentiated thyroid cancer:results of a multicenter phase II international thyroid oncology group trial[J].J Clin Oncol,2017,35(29):3315-3321.
[18]Cohen EE,Tortorici M,Kim S,et al.A Phase II trial of axitinib in patients with various histologic subtypes of advanced thyroid cancer:long-term outcomes and pharmacokinetic/pharmacodynamic analyses[J].Cancer Chemother Pharmacol,2014,74(6):1261-1270.
[19]Capdevila J,Trigo JM,Aller J,et al.Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer(DTC)and refractory medullary thyroid cancer(MTC)[J].Eur J Endocrinol,2017,177(4):309-317.
[20]Hayes DN,Lucas AS,Tanvetyanon T,et al.Phase II efficacy and pharmacogenomic study of Selumetinib(AZD6244;ARRY-142886)in iodine-131 refractory papillary thyroid carcinoma with or without follicular elements[J].Clin Cancer Res,2012,18(7):2056-2065.
[21]Ho AL,Grewal RK,Leboeuf R,et al.Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer[J].N Engl J Med,2013,368(7):623-632.
[22]Bible KC,Suman VJ,Molina JR,et al.A multicenter phase 2trial of pazopanib in metastatic and progressive medullary thyroid carcinoma:MC057H[J].J Clin Endocrinol Metab,2014,99(5):1687-1693.
[23]Ball DW,Jin N,Xue P,et al.Trametinib with and without pazopanib has potent preclinical activity in thyroid cancer[J].Oncol Rep,2015,34(5):2319-2324.
[24]Dadu R,Shah K,Busaidy NL,et al.Efficacy and tolerability of vemurafenib in patients with BRAF(V600E)-positive papillary thyroid cancer:M.D.Anderson Cancer Center off label experience[J].J Clin Endocrinol Metab,2015,100(1):77-81.
[25]Schneider TC,De WD,Links TP,et al.Everolimus in patients with advanced follicular-derived thyroid cancer:Results of a phase II clinical trial[J].J Clin Endocrinol Metab,2017,102(2):698-707.
[26]Wit DD,Schneider TC,Moes DJAR,et al.Everolimus pharmacokinetics and its exposure-toxicity relationship in patients with thyroid cancer[J].Cancer Chemoth Pharm,2016,78(1):63-71.
[27]Jin Z,Cheng X,Feng H,et al.Apatinib inhibits angiogenesis via suppressing Akt/GSK3β/ANG signaling pathway in anaplastic thyroid cancer[J].Cell Physiol Biochem,2017,44(4):1471-1484.
[28]Lin Y,Chen W,Wen G,et al.Overwhelming rapid metabolic and structural response to apatinib in radioiodine refractory differentiated thyroid cancer[J].Oncotarget,2017,8(26):42252-42261.
[2]Ferrari SM,Politti U,Spisni R,et al.Sorafenib in the treatment of thyroid cancer[J].Expert Rev Anticancer Ther,2015,15(8):863-874.
[3]Brose MS,Nutting CM,Jarzab B,et al.Sorafenib in radioactive iodine-refractory,locally advanced or metastatic differentiated thyroid cancer:a randomised,double-blind,phase 3 trial[J].Lancet,2014,384(9940):319-328.
[4]Ito Y,Onoda N,Ito KI,et al.Sorafenib in Japanese patients with locally advanced or metastatic medullary thyroid carcinoma and anaplastic thyroid carcinoma[J].Thyroid,2017,27(9):1142-1148.
[5]Fallahi P,Di FB,Ferrari SM,et al.Selective use of vandetanib in the treatment of thyroid cancer[J].Drug Design Development AND Therapy,2015,9:3459-3470.
[6]Chougnet CN,Borget I,Leboulleux S,et al.Vandetanib for the treatment of advanced medullary thyroid cancer outside a clinical trial:results from a French cohort[J].Thyroid,2015,25(4):386-391.
[7]Uchino K,Komoda M,Tomomatsu J,et al.Safety and tolerability of vandetanib in Japanese patients with medullary thyroid cancer:A phase I/II open-label study[J].Endocr Pract,2017,23(2):149-156.
[8]Brose MS,Worden FP,Newbold KL,et al.Effect of age on the efficacy and safety of lenvatinib in radioiodine-refractory differentiated thyroid cancer in the phase III select trial[J].J Clin Oncol,2017,35(23):2692-2699.
[9]Robinson B,Schlumberger M,Wirth LJ,et al.Characterization of tumor size changes over time from the phase 3 study of lenvatinib in thyroid cancer[J].J Clin Endocrinol Metab,2016,101(11):4103-4109.
[10]Schlumberger M,Jarzab B,Cabanillas ME,et al.A phase II trial of the multitargeted tyrosine kinase inhibitor lenvatinib(E7080)in advanced medullary thyroid cancer[J].Clin Cancer Res,2012,22(1):44-53.
[11]Lorusso L,Newbold K.Lenvatinib:a new option for the treatment of advanced iodine refractory differentiated thyroid cancer?[J].Future Oncol,2015,11(12):1719-1727.
[12]Schlumberger M,Tahara M,Wirth LJ,et al.Lenvatinib versus placebo in radioiodine-refractory thyroid cancer[J].N Engl JMed,2015,372(7):621-630.
[13]I iguez-Ariza NM,Ryder MM,Hilger CR,et al.Salvage lenvatinib therapy in metastatic anaplastic thyroid cancer[J].Thyroid,2017,27(7):923-927.
[14]Krajewska J,Olczyk T,Jarzab B.Cabozantinib for the treatment of progressive metastatic medullary thyroid cancer[J].Expert Rev Clin Pharmacol,2016,9(1):69-79.
[15]Schlumberger M,Elisei R,Müller S,et al.Overall survival analysis of EXAM,a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma[J].Ann Oncol,2017,28(11):2813-2819.
[16]Belum VR,Serna-Tamayo C,Wu S,et al.Incidence and risk of hand-foot skin reaction with cabozantinib,a novel multikinase inhibitor:a meta-analysis[J].Clin Exp Dermatol,2016,41(1):8-15.n
[17]Cabanillas ME,de Souza JA,Geyer S,et al.Cabozantinib as salvage therapy for patients with tyrosine kinase inhibitor-refractory differentiated thyroid cancer:results of a multicenter phase II international thyroid oncology group trial[J].J Clin Oncol,2017,35(29):3315-3321.
[18]Cohen EE,Tortorici M,Kim S,et al.A Phase II trial of axitinib in patients with various histologic subtypes of advanced thyroid cancer:long-term outcomes and pharmacokinetic/pharmacodynamic analyses[J].Cancer Chemother Pharmacol,2014,74(6):1261-1270.
[19]Capdevila J,Trigo JM,Aller J,et al.Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer(DTC)and refractory medullary thyroid cancer(MTC)[J].Eur J Endocrinol,2017,177(4):309-317.
[20]Hayes DN,Lucas AS,Tanvetyanon T,et al.Phase II efficacy and pharmacogenomic study of Selumetinib(AZD6244;ARRY-142886)in iodine-131 refractory papillary thyroid carcinoma with or without follicular elements[J].Clin Cancer Res,2012,18(7):2056-2065.
[21]Ho AL,Grewal RK,Leboeuf R,et al.Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer[J].N Engl J Med,2013,368(7):623-632.
[22]Bible KC,Suman VJ,Molina JR,et al.A multicenter phase 2trial of pazopanib in metastatic and progressive medullary thyroid carcinoma:MC057H[J].J Clin Endocrinol Metab,2014,99(5):1687-1693.
[23]Ball DW,Jin N,Xue P,et al.Trametinib with and without pazopanib has potent preclinical activity in thyroid cancer[J].Oncol Rep,2015,34(5):2319-2324.
[24]Dadu R,Shah K,Busaidy NL,et al.Efficacy and tolerability of vemurafenib in patients with BRAF(V600E)-positive papillary thyroid cancer:M.D.Anderson Cancer Center off label experience[J].J Clin Endocrinol Metab,2015,100(1):77-81.
[25]Schneider TC,De WD,Links TP,et al.Everolimus in patients with advanced follicular-derived thyroid cancer:Results of a phase II clinical trial[J].J Clin Endocrinol Metab,2017,102(2):698-707.
[26]Wit DD,Schneider TC,Moes DJAR,et al.Everolimus pharmacokinetics and its exposure-toxicity relationship in patients with thyroid cancer[J].Cancer Chemoth Pharm,2016,78(1):63-71.
[27]Jin Z,Cheng X,Feng H,et al.Apatinib inhibits angiogenesis via suppressing Akt/GSK3β/ANG signaling pathway in anaplastic thyroid cancer[J].Cell Physiol Biochem,2017,44(4):1471-1484.
[28]Lin Y,Chen W,Wen G,et al.Overwhelming rapid metabolic and structural response to apatinib in radioiodine refractory differentiated thyroid cancer[J].Oncotarget,2017,8(26):42252-42261.