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Abstract: breast cancer is one of the malignant tumors with the highest morbidity and mortality. It is helpful to reduce the rate of tumor recurrence and metastasis by treating breast cancer with adjuvant chemotherapy, so as to increase the cure rate or survival of patients. In recent years, liposomes have been regarded as a kind of new carrier for targeted drugs. Being effective for enhancing drug efficacy and reducing side effects, they have been widely used for developing anticancer drugs. As a kind of anthracycline with high anticancer activity, doxorubicin can treat or alleviate a variety of malignant tumors effectively when it is used on its own or in combination with other anticancer drugs. Although liposomal doxorubicin has been extensively used in the adjuvant chemotherapy of breast cancer, its exact therapeutic efficacy and side effects have not been definitely proven. Various clinical studies have adopted different combined regimes, dosages, and staging, so their findings differ to certain extent. This paper reviews the clinical application of liposomal doxorubicin in the adjuvant chemotherapy of breast cancer and illustrates therapeutic effects and side effects of pegylated liposomal doxorubicin (PLD) and non-PLD (NPLD) in clinical research, in order to discuss the strategies for applying these drugs in such adjuvant chemotherapy, looking forward to providing references for related research and clinical treatment in terms of dosage, staging, combined regimes, and analysis methods and so on.

多柔比星脂质体在乳腺癌辅助化疗中的临床应用

[1]Abdel-Fatah, T.M., Perry, C., Dickinson, P., et al., 2013. Bcl2 is an independent prognostic marker of triple negative breast cancer (TNBC) and predicts response to anthracycline combination (ATC) chemotherapy (CT) in adjuvant and neoadjuvant settings. Ann. Oncol., 24(11):2801-2807.

[2]Addeo, R., Faiola, V., Guarrasi, R., et al., 2008. Liposomal pegylated doxorubicin plus vinorelbine combination as first-line chemotherapy for metastatic breast cancer in elderly women > or =65 years of age. Cancer Chemother. Pharmacol., 62(2):285-292.

[3]Airoldi, M., Amadori, D., Barni, S., et al., 2011. Clinical activity and cardiac tolerability of non-pegylated liposomal doxorubicin in breast cancer: a synthetic review. Tumori, 97(6):690-692.

[4]Anders, C.K., Adamo, B., Karginova, O., et al., 2013. Pharmacokinetics and efficacy of PEGylated liposomal doxorubicin in an intracranial model of breast cancer. PLoS ONE, 8(5):e61359.

[5]Antón, A., Ruiz, A., Plazaola, A., et al., 2011. Phase II clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neoadjuvant treatment in stages II and IIIA HER-2-overexpressing breast cancer patients. GEICAM 2003-03 study. Ann. Oncol., 22(1):74-79.

[6]Artioli, G., Mocellin, S., Borgato, L., et al., 2010. Phase II study of neoadjuvant gemcitabine, pegylated liposomal doxorubicin, and docetaxel in locally advanced breast cancer. Anticancer Res., 30(9):3817-3821.

[7]Bangham, A.D., Standish, M.M., Watkins, J.C., 1965. Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol., 13(1):238-252.

[8]Baselga, J., Manikhas, A., Cortés, J., et al., 2014. Phase III trial of nonpegylated liposomal doxorubicin in combination with trastuzumab and paclitaxel in HER-2-positive metastatic breast cancer. Ann. Oncol., 25(3):592-598.

[9]Basso, U., Roma, A., Brunello, A., et al., 2013. Bi-weekly liposomal doxorubicin for advanced breast cancer in elderly women (≥70 years). J. Geriatr. Oncol., 4(4):340-345.

[10]Bear, H.D., Anderson, S., Brown, A., et al., 2003. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J. Clin. Oncol., 21(22):4165-4174.

[11]Chen, S., Jiang, Y.Z., Huang, L., et al., 2013. The residual tumor autophagy marker LC3B serves as a prognostic marker in local advanced breast cancer after neoadjuvant chemotherapy. Clin. Cancer Res., 19(24):6853-6862.

[12]Davidson, N., Camburn, T., Keary, I., et al., 2014. Substituting doxorubicin with nonpegylated liposomal doxorubicin for the treatment of early breast cancer: results of a retrospective study. Int. J. Breast Cancer, 2014:984067.

[13]Dellapasqua, S., Mazza, M., Rosa, D., et al., 2011. Pegylated liposomal doxorubicin in combination with low-dose metronomic cyclophosphamide as preoperative treatment for patients with locally advanced breast cancer. Breast, 20(4):319-323.

[14]Duggan, S.T., Keating, G.M., 2011. Pegylated liposomal doxorubicin: a review of its use in metastatic breast cancer, ovarian cancer, multiple myeloma and AIDS-related Kaposi’s sarcoma. Drugs, 71(18):2531-2558.

[15]Franchina, T., Adamo, B., Ricciardi, G.R., et al., 2012. Activity of pegylated liposomal doxorubicin in combination with gemcitabine in triple negative breast cancer with skin involvement: two case reports. Cancer Biol. Ther., 13(7):472-476.

[16]Gagliato, D.M., Jardim, D.L., Marchesi, M.S., et al., 2016. Mechanisms of resistance and sensitivity to anti-HER2 therapies in HER2+ breast cancer. Oncotarget, 7(39):64431-64446.

[17]Gavilá, J., Guerrero, Á., Climent, M.Á., et al., 2015. Efficacy and safety of neoadjuvant chemotherapy with concurrent liposomal-encapsulated doxorubicin, paclitaxel and trastuzumab for human epidermal growth factor receptor 2-positive breast cancer in clinical practice. Int. J. Clin. Oncol., 20(3):480-489.

[18]Goel, P.N., Gude, R.P., 2014. Delineating the anti-metastatic potential of pentoxifylline in combination with liposomal doxorubicin against breast cancer cells. Biomed. Pharmacother., 68(2):191-200.

[19]Gogas, H., Papadimitriou, C., Kalofonos, H.P., et al., 2002. Neoadjuvant chemotherapy with a combination of pegylated liposomal doxorubicin (Caelyx) and paclitaxel in locally advanced breast cancer: a phase II study by the Hellenic Cooperative Oncology Group. Ann. Oncol., 13(11):1737-1742.

[20]Greish, K., Sawa, T., Fang, J., et al., 2004. SMA-doxorubicin, a new polymeric micellar drug for effective targeting to solid tumours. J. Control. Release, 97(2):219-230.

[21]Hortobágyi, G.N., 1997. Anthracyclines in the treatment of cancer. An overview. Drugs, 54(Suppl. 4):1-7.

[22]Jehn, C.F., Hemmati, P., Lehenbauer-Dehm, S., et al., 2016. Biweekly pegylated liposomal doxorubicin (Caelyx) in heavily pretreated metastatic breast cancer: a phase 2 study. Clin. Breast Cancer, 16(6):514-519.

[23]Karpinska, A., Safranow, K., Kładny, J., et al., 2015. The influence of obesity on results of AT (doxorubicin plus docetaxel) neoadjuvant chemotherapy in locally advanced breast cancer patients. Pol. Przegl. Chir., 87(5):231-237.

[24]Kim, H.J., Im, S.A., Keam, B., et al., 2015. ABCB1 polymorphism as prognostic factor in breast cancer patients treated with docetaxel and doxorubicin neoadjuvant chemotherapy. Cancer Sci., 106(1):86-93.

[25]Kong, G., Anyarambhatla, G., Petros, W.P., et al., 2000. Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release. Cancer Res., 60(24):6950-6957.

[26]Lien, M.Y., Liu, L.C., Wang, H.C., et al., 2014. Safety and efficacy of pegylated liposomal doxorubicin-based adjuvant chemotherapy in patients with stage I–III triple-negative breast cancer. Anticancer Res., 34(12):7319-7326.

[27]Linot, B., Campone, M., Augereau, P., et al., 2014. Use of liposomal doxorubicin cyclophosphamide combination in breast cancer patients with brain metastases: a monocentric retrospective study. J. Neuro-Oncol., 117(2):253-259.

[28]Lu, Y.C., Ou-Yang, F., Hsieh, C.M., et al., 2016. Pegylated liposomal doxorubicin as adjuvant therapy for stage I-III operable breast cancer. In Vivo, 32(2):159-163.

[29]Minotti, G., Menna, P., Salvatorelli, E., et al., 2004. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev., 56(2):185-229.

[30]Mitra, S., Gaur, U., Ghosh, P.C., et al., 2001. Tumour targeted delivery of encapsulated dextran-doxorubicin conjugate using chitosan nanoparticles as carrier. J. Control. Release, 74(1-3):317-323.

[31]O'Reilly, E.A., Gubbins, L., Sharma, S., et al., 2016. The fate of chemoresistance in triple negative breast cancer (TNBC). BBA Clin., 3(3):257-275.

[32]Palmieri, C., Misra, V., Januszewski, A., et al., 2014. Multicenter experience of nonpegylated liposomal doxorubicin use in the management of metastatic breast cancer. Clin. Breast Cancer, 14(2):85-93.

[33]Petersen, G.H., Alzghari, S.K., Chee, W., et al., 2016. Meta-analysis of clinical and preclinical studies comparing the anticancer efficacy of liposomal versus conventional non-liposomal doxorubicin. J. Control. Release, 232:255-264.

[34]Pircher, M., Mlineritsch, B., Fridrik, M.A., et al., 2015. Lapatinib-plus-pegylated liposomal doxorubicin in advanced HER-2-positive breast cancer following trastuzumab: a phase II trial. Anticancer Res., 35(1):517-521.

[35]Rau, K.M., Lin, Y.C., Chen, Y.Y., et al., 2015. Pegylated liposomal doxorubicin (Lipo-Dox^®) combined with cyclophosphamide and 5-fluorouracil is effective and safe as salvage chemotherapy in taxane-treated metastatic breast cancer: an open-label, multi-center, non-comparative phase II study. BMC Cancer, 15:423-431.

[36]Rossi, D., Baldelli, A.M., Casadei, V., et al., 2008. Neoadjuvant chemotherapy with low dose of pegylated liposomal doxorubicin plus weekly paclitaxel in operable and locally advanced breast cancer. Anti-Cancer Drugs, 19(7):733-737.

[37]Ryman, B.E., Whelan, W.J., 1971. New aspects of glycogen metabolism. Adv. Enzymol. Relat. Areas Mol. Biol., 34(4):285-443.

[38]Saracchini, S., Foltran, L., Tuccia, F., et al., 2013. Phase II study of liposome-encapsulated doxorubicin plus cyclophosphamide, followed by sequential trastuzumab plus docetaxel as primary systemic therapy for breast cancer patients with HER-2 overexpression or amplification. Breast, 22(6):1101-1107.

[39]Schmid, P., Krocker, J., Schulz, C.O., et al., 2005a. Primary chemotherapy with gemcitabine, liposomal doxorubicin and docetaxel in patients with locally advanced breast cancer: results of a phase I trial. Anti-Cancer Drugs, 16(1):21-29.

[40]Schmid, P., Krocker, J., Jehn, C., et al., 2005b. Primary chemotherapy with gemcitabine as prolonged infusion, non-pegylated liposomal doxorubicin and docetaxel in patients with early breast cancer: final results of a phase II trial. Ann. Oncol., 16(10):1624-1631.

[41]Siegel, R., Ma, J., Zou, Z.H., 2014. Cancer statistics, 2014. CA Cancer J. Clin., 64(1):9-29.

[42]Smorenburg, C.H., de Groot, S.M., van Leeuwen-Stok, A.E., et al., 2014. A randomized phase III study comparing pegylated liposomal doxorubicin with capecitabine as first-line chemotherapy in elderly patients with metastatic breast cancer: results of the OMEGA study of the Dutch Breast Cancer Research Group BOOG. Ann. Oncol., 25(3):599-605.

[43]Sparano, J.A., Makhson, A.N., Semiglazov, V.F., et al., 2009. Pegylated liposomal doxorubicin plus docetaxel significantly improves time to progression without additive cardiotoxicity compared with docetaxel monotherapy in patients with advanced breast cancer previously treated with neoadjuvant-adjuvant anthracycline therapy: results from a randomized phase III study. J. Clin. Oncol., 27(27):4522-4529.

[44]Templeton, A.J., Ribi, K., Surber, C., et al., 2014. Prevention of palmar–plantar erythrodysesthesia with an antiperspirant in breast cancer patients treated with pegylated liposomal doxorubicin (SAKK 92/08). Breast, 23(3):244-249.

[45]Torrisi, R., Montagna, E., Scarano, E., et al., 2011. Neoadjuvant pegylated liposomal doxorubicin in combination with cisplatin and infusional fluoruracil (CCF) with and without endocrine therapy in locally advanced primary or recurrent breast cancer. Breast, 20(1):34-38.

[46]Tuxen, M.K., Cold, S., Tange, U.B., et al., 2014. Phase II study of neoadjuvant pegylated liposomal doxorubicin and cyclophosphamide±trastuzumab followed by docetaxel in locally advanced breast cancer. Acta Oncol., 53(10):1440-1445.

[47]Tyagi, P., Wu, P.C., Chancellor, M., et al., 2006. Recent advances in intravesical drug/gene delivery. Mol. Pharm., 3(4):369-379.

[48]Uriarte-Pinto, M., Escolano-Pueyo, Á., Gimeno-Ballester, V., et al., 2016. Trastuzumab, non-pegylated liposomal-encapsulated doxorubicin and paclitaxel in the neoadjuvant setting of HER-2 positive breast cancer. Int. J. Clin. Pharm., 38(2):446-453.

[49]Vici, P., Pizzuti, L., Gamucci, T., et al., 2014. Non-pegylated liposomal doxorubicin cyclophosphamide in sequential regimens with taxanes as neoadjuvant chemotherapy in breast cancer patients. J. Cancer, 5(6):398-405.

[50]Vujaskovic, Z., Kim, D.W., Jones, E., et al., 2010. A phase I/II study of neoadjuvant liposomal doxorubicin, paclitaxel, and hyperthermia in locally advanced breast cancer. Int. J. Hyperthermia, 26(5):514-521.

[51]Wu, S.K., Chiang, C.F., Hsu, Y.H., et al., 2014. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer. Int. J. Nanomed., 9(9):4485-4494.

[52]Xing, M., Yan, F., Yu, S., et al., 2015. Efficacy and cardiotoxicity of liposomal doxorubicin-based chemotherapy in advanced breast cancer: a meta-analysis of ten randomized controlled trials. PLoS ONE, 10(7):e0133569.

[53]Xu, S., Wei, Q., Guo, J., et al., 2015. FOXA1 expression significantly predict response to chemotherapy in estrogen receptor-positive breast cancer patients. Ann. Surg. Oncol., 22(6):2034-2039.

[54]Yokoyama, M., 2005. Drug targeting with nano-sized carrier systems. J. Artif. Organs, 8(2):77-84.

[55]Yoo, H.S., Lee, E.A., Park, T.G., 2002. Doxorubicin-conjugated biodegradable polymeric micelles having acid-cleavable linkages. J. Control. Release, 82(1):17-27.

[56]Zagar, T.M., Vujaskovic, Z., Formenti, S., et al., 2014. Two phase I dose-escalation/pharmacokinetics studies of low temperature liposomal doxorubicin (LTLD) and mild local hyperthermia in heavily pretreated patients with local regionally recurrent breast cancer. Int. J. Hyperthermia, 30(5):285-294.