Nab-paclitaxel: potential for the treatment of advanced pancreatic cancer

Marwan Al-Hajeili, Asfar S Azmi, Minsig Choi, Marwan Al-Hajeili, Asfar S Azmi, Minsig Choi

Abstract

Advanced pancreatic adenocarcinoma is a deadly disease and is considered incurable. For the past two decades, gemcitabine remained the major chemotherapeutic drug with modest clinical benefit. Many chemotherapy and targeted agents were combined with gemcitabine but failed to demonstrate improvement in pancreatic cancer (PC) survival. Taxanes (paclitaxel, docetaxel) were introduced in the clinic as anti-microtubule agents and showed activity against PC cells in vitro; however, clinical efficacy was limited. Nab-paclitaxel (Abraxane) is an albumin-bound paclitaxel that has shown clinical activity in advanced breast and lung cancer. Recently, nab-paclitaxel was tested in a large Phase III clinical trial in combination with gemcitabine for the treatment of advanced PC. The data showed that the addition of nab-paclitaxel improved the response rate (7% in gemcitabine alone versus 23% in combination), progression-free survival (from 3.7 months to 5.5 months), and overall survival from 6.7 months to 8.5 months, compared to single agent gemcitabine. Through this review, we provide the preclinical and clinical progress in the development of nab-paclitaxel for the treatment of metastatic PC.

Keywords: abraxane; gemcitabine; nab-paclitaxel; pancreatic adenocarcinoma.

References

    1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.
    1. Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet. 2004;363(9414):1049–1057.
    1. Maitra A, Kern SE, Hruban RH. Molecular pathogenesis of pancreatic cancer. Best Pract Res Clin Gastroenterol. 2006;20(2):211–226.
    1. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011;378(9791):607–620.
    1. Tanase CP, Neagu M, Albulescu R, Hinescu ME. Advances in pancreatic cancer detection. Adv Clin Chem. 2010;51:145–180.
    1. Abbruzzese JL. Adjuvant therapy for surgically resected pancreatic adenocarcinoma. JAMA. 2008;299(9):1066–1067.
    1. Burris HA, 3rd, 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(6):2403–2413.
    1. Wang Z, Li Y, Kong D, et al. Acquisition of epithelial-mesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway. Cancer Res. 2009;69(6):2400–2407.
    1. Frese KK, Neesse A, Cook N, et al. nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer Discov. 2012;2(3):260–269.
    1. Hong SP, Wen J, Bang S, Park S, Song SY. CD44-positive cells are responsible for gemcitabine resistance in pancreatic cancer cells. Int J Cancer. 2009;125(10):2323–2331.
    1. 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(15):1960–1966.
    1. Belli C, Cereda S, Reni M. Role of taxanes in pancreatic cancer. World J Gastroenterol. 2012;18(33):4457–4465.
    1. Rowinsky EK, Calvo E. Novel agents that target tublin and related elements. Semin Oncol. 2006;33(4):421–435.
    1. Yared JA, Tkaczuk KH. Update on taxane development: new analogs and new formulations. Drug Des Devel Ther. 2012;6:371–384.
    1. Weiss RB, Donehower RC, Wiernik PH, et al. Hypersensitivity reactions from taxol. J Clin Oncol. 1990;8(7):1263–1268.
    1. Shepherd GM. Hypersensitivity reactions to chemotherapeutic drugs. Clin Rev Allergy Immunol. 2003;24(3):253–262.
    1. Cordes N, Plasswilm L. Cell line and schedule-dependent cytotoxicity of paclitaxel (Taxol): role of the solvent Cremophor EL/ethanol. Anticancer Res. 1998;18(3A):1851–1857.
    1. Okada S, Sakata Y, Matsuno S, et al. Phase II study of docetaxel in patients with metastatic pancreatic cancer: a Japanese cooperative study. Cooperative Group of Docetaxel for Pancreatic Cancer in Japan. Br J Cancer. 1999;80(3–4):438–443.
    1. Androulakis N, Kourousis C, Dimopoulos MA, et al. Treatment of pancreatic cancer with docetaxel and granulocyte colony-stimulating factor: a multicenter phase II study. J Clin Oncol. 1999;17(6):1779–1785.
    1. Rougier P, Adenis A, Ducreux M, et al. A phase II study: docetaxel as first-line chemotherapy for advanced pancreatic adenocarcinoma. Eur J Cancer. 2000;36(8):1016–1025.
    1. Ryan DP, Kulke MH, Fuchs CS, et al. A Phase II study of gemcitabine and docetaxel in patients with metastatic pancreatic carcinoma. Cancer. 2002;94(1):97–103.
    1. Stathopoulos GP, Mavroudis D, Tsavaris N, et al. Treatment of pancreatic cancer with a combination of docetaxel, gemcitabine and granulocyte colony-stimulating factor: a phase II study of the Greek Cooperative Group for Pancreatic Cancer. Ann Oncol. 2001;12(1):101–103.
    1. Sparreboom A, Scripture CD, Trieu V, et al. Comparative preclinical and clinical pharmacokinetics of a cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in Cremophor (Taxol) Clin Cancer Res. 2005;11(11):4136–4143.
    1. 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):4200–4205.
    1. 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):1317–1324.
    1. Desai NP, Trieu V, Hwang LY, Wu R, Soon-Shiong P, Gradishar WJ. Improved effectiveness of nanoparticle albumin-bound (nab) paclitaxel versus polysorbate-based docetaxel in multiple xenografts as a function of HER2 and SPARC status. Anticancer Drugs. 2008;19(9):899–909.
    1. Watkins G, Douglas-Jones A, Bryce R, Mansel RE, Jiang WG. Increased levels of SPARC (osteonectin) in human breast cancer tissues and its association with clinical outcomes. Prostaglandins Leukot Essent Fatty Acids. 2005;72(4):267–272.
    1. Watkins G, Martin TA, Bryce R, Mansel RE, Jiang WG. Gamma-linolenic acid regulates the expression and secretion of SPARC in human cancer cells. Prostaglandins Leukot Essent Fatty Acids. 2005;72(4):273–278.
    1. Desai N, Trieu V, Damascelli B, Soon-Shiong P. SPARC expression correlates with tumor response to albumin-bound paclitaxel in head and neck cancer patients. Transl Oncol. 2009;2(2):59–64.
    1. Neuzillet C, Tijeras-Raballand A, Cros J, Faivre S, Hammel P, Raymond E. Stromal expression of SPARC in pancreatic adenocarcinoma. Cancer Metastasis Rev. 2013;32(3–4):585–602.
    1. Infante JR, Matsubayashi H, Sato N, et al. Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. J Clin Oncol. 2007;25(3):319–325.
    1. Von Hoff DD, Ramanathan RK, Borad MJ, 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;29(34):4548–4554.
    1. Neesse A, Frese KK, Chan DS, et al. SPARC independent drug delivery and antitumour effects of nab-paclitaxel in genetically engineered mice. Gut. 2013 Sep 25; Epub.
    1. Chu GC, Kimmelman AC, Hezel AF, DePinho RA. Stromal biology of pancreatic cancer. J Cell Biochem. 2007;101(4):887–907.
    1. Hidalgo M, Von Hoff DD. Translational therapeutic opportunities in ductal adenocarcinoma of the pancreas. Clin Cancer Res. 2012;18(16):4249–4256.
    1. Mahadevan D, Von Hoff DD. Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther. 2007;6(4):1186–1197.
    1. Alvarez R, Musteanu M, Garcia-Garcia E, et al. Stromal disrupting effects of nab-paclitaxel in pancreatic cancer. Br J Cancer. 2013;109(4):926–933.
    1. Von Hoff DD, Bearss D. New drugs for patients with pancreatic cancer. Curr Opin Oncol. 2002;14(6):621–627.
    1. Zhang DS, Wang DS, Wang ZQ, et al. Phase I/II study of albumin-bound nab-paclitaxel plus gemcitabine administered to Chinese patients with advanced pancreatic cancer. Cancer Chemother Pharmacol. 2013;71(4):1065–1072.
    1. 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):1691–1703.
    1. Nyman DW, Campbell KJ, Hersh E, et al. Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. J Clin Oncol. 2005;23(31):7785–7793.
    1. Gradishar WJ, Tjulandin S, Davidson N, et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005;23(31):7794–7803.
    1. Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012;30(17):2055–2062.
    1. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–1825.
    1. Bendell JCBS, Green MR, Willey J, Lemke KE, Marshall J. Immediate impact of the FOLFIRINOX phase III data reported at the 2010 ASCO Annual Meeting on prescribing plans of American oncology physicians for patients with metastatic pancreas cancer (MPC) J Clin Oncol. 2011;29(Suppl 4) Abstract 286.
    1. Gill S, Ho MY, Kennecke HF, Renouf DJ, Cheung WY, Lim HJ. Defining eligibility of FOLFIRINOX for the first-line metastatic pancreatic adenocarcinoma (MPC) in the province of the British Columbia: a population based retrospective study. J Clin Oncol. 2012;30(Suppl) Abstract e14588.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe