Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Breast Cancer: Results from a Multicenter Retrospective Study

Sundaram Subramanian, Rammohan Prasanna, Ghanashyam Biswas, Saroj Kumar Das Majumdar, Nisarg Joshi, Deepak Bunger, Mujtaba A Khan, Imran Ahmad, Sundaram Subramanian, Rammohan Prasanna, Ghanashyam Biswas, Saroj Kumar Das Majumdar, Nisarg Joshi, Deepak Bunger, Mujtaba A Khan, Imran Ahmad

Abstract

Purpose: The purpose of this study was to evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip)-based chemotherapy in breast cancer.

Methods: Medical charts of patients with breast cancer, who were treated and followed up with NDLS (75-100 mg/m2; 3-week cycle)-based chemotherapy from August 2014 to September 2018, were analyzed in this multicenter, retrospective study. The study endpoints were overall response rate (ORR: complete response [CR]+partial response [PR]) and disease control rate (DCR: CR+PR+stable disease [SD]) in neoadjuvant and metastatic settings. Overall survival (OS) and safety were evaluated for all settings.

Results: Of 91 patients (neoadjuvant: 12, adjuvant: 61, metastatic: 18), efficacy evaluation in 29 patients (neoadjuvant: 12/12, metastatic: 17/18) demonstrated an ORR and DCR of 100%, respectively, in the neoadjuvant setting, and an ORR of 64.7% and DCR of 70.6%, respectively, in the metastatic setting. At a median follow-up of 21.6 months (range: 2.1 to 49.9 months), median OS was not reached in neoadjuvant and adjuvant settings, and it was 30.4 months in metastatic settings. At least one adverse event (AE) was reported in 59.3% of patients. Anemia, thrombocytopenia, lymphopenia, and neutropenia were the most common hematological AEs reported while hyperglycemia and alteration in liver function tests were the most common non-hematological AEs. NDLS-based treatment was well tolerated without any new safety concerns.

Conclusion: Nanosomal docetaxel lipid suspension-based chemotherapy was efficacious and well tolerated in the treatment of breast cancer. Further, NDLS is being evaluated prospectively in patients with triple-negative breast cancer (ClinicalTrials.gov: NCT03671044).

Keywords: DoceAqualip; NDLS; breast cancer; nanosomal docetaxel lipid suspension.

Conflict of interest statement

Drs Mujtaba A Khan, Deepak Bunger and Nisarg Joshi are employees of Intas Pharmaceuticals Ltd., India, and the product being mentioned is manufactured and marketed by Intas Ltd. Dr Imran Ahmad is an employee of Jina Pharmaceuticals Inc., USA. The authors report no other conflicts of interest in this work.

© 2020 Subramanian et al.

Figures

Figure 1
Figure 1
Response rate of NDLS-based chemotherapy in breast cancer in (A) neoadjuvant setting (n=12), and (B) metastatic setting (n=17). Abbreviations: CR, complete response; DCR, disease control rate; NDLS, nanosomal docetaxel lipid suspension; ORR, overall response rate; PR, partial response; SD, stable disease.
Figure 2
Figure 2
Kaplan–Meier estimates of overall survival in breast cancer patients: (A) neoadjuvant (n=12), (B) adjuvant (n=61), and (C) metastatic (n=18) settings. The mean survival time and its standard error were underestimated because the largest observation was censored and estimation was restricted to the largest event time.

References

    1. Ghoncheh M, Pournamdar Z, Salehiniya H. Incidence and mortality and epidemiology of breast cancer in the world. Asian Pac J Cancer Prev. 2016;17(S3):43–46. doi:10.7314/APJCP.2016.17.S3.43
    1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi:10.3322/caac.21492
    1. National Institute for Cancer Prevention and Research. Globocan 2018: India Factsheet. Available from: . Accessed April21, 2020.
    1. Crown J, O’Leary M, Ooi WS. Docetaxel and paclitaxel in the treatment of breast cancer: a review of clinical experience. Oncologist. 2004;9Suppl 2(S2):24–32. doi:10.1634/theoncologist.9-suppl_2-24
    1. Taxotere® Prescribing Information. sanofi-aventis U.S. LLC, NJ 08807. Revised May, 2010.
    1. Amat S, Bougnoux P, Penault-Llorca F, et al. Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate. Br J Cancer. 2003;88(9):1339–1345. doi:10.1038/sj.bjc.6600916
    1. von Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796–1804. doi:10.1200/JCO.2011.38.8595
    1. Weiszhár Z, Czúcz J, Révész C, et al. Complement activation by polyethoxylated pharmaceutical surfactants: cremophor-EL, Tween-80 and Tween-20. Eur J Pharm Sci. 2012;45(4):492–498. doi:10.1016/j.ejps.2011.09.016
    1. Pritchett W, Kinsley K. Benefits and risks of fosaprepitant in patients receiving emetogenic regimens. Clin J Oncol Nurs. 2016;20(5):555–556. doi:10.1188/16.CJON.555-556
    1. Fumoleau P, Tubiana-Hulin M, Soulie P, et al. A dose finding and pharmacokinetic (PK) Phase I study of a new formulation of docetaxel (D) in advanced solid tumors. [abstract]. Ann Oncol. 1998;9(Suppl. 2):101.
    1. Ten Tije AJ, Verweij J, Loos WJ, Sparreboom A. Pharmacological effects of formulation vehicles: implications for cancer chemotherapy. Clin Pharmacokinet. 2003;42(7):665–685. doi:10.2165/00003088-200342070-00005
    1. Coors EA, Seybold H, Merk HF, Mahler V. Polysorbate 80 in medical products and nonimmunologic anaphylactoid reactions. Ann Allergy Asthma Immunol. 2005;95(6):593–599. doi:10.1016/S1081-1206(10)61024-1
    1. Schwartzberg LS, Navari RM. Safety of polysorbate 80 in the oncology setting. Adv Ther. 2018;35(6):754–767. doi:10.1007/s12325-018-0707-z
    1. FDA Drug Safety Communication (2014, June 20). FDA warns that cancer drug docetaxel may cause symptoms of alcohol intoxication after treatment. Available From: . Accessed April21, 2020.
    1. Mirza A, Mithal N. Alcohol intoxication with the new formulation of docetaxel. Clin Oncol (R Coll Radiol). 2011;23(8):560–561. doi:10.1016/j.clon.2011.04.010
    1. Piccart MJ, Klijn J, Paridaens R, et al. Corticosteroids significantly delay the onset of docetaxel-induced fluid retention: final results of a randomized study of the European organization for research and treatment of cancer investigational drug branch for breast cancer. J Clin Oncol. 1997;15(9):3149–3155. doi:10.1200/JCO.1997.15.9.3149
    1. Jung JW, Choi YH, Park CM, et al. Outcomes of corticosteroid prophylaxis for hypersensitivity reactions to low osmolar contrast media in high-risk patients. Ann Allergy Asthma Immunol. 2016;117(3):304–309.e301. doi:10.1016/j.anai.2016.07.010
    1. Alken S, Kelly CM. Benefit risk assessment and update on the use of docetaxel in the management of breast cancer. Cancer Manag Res. 2013;5:357–365. doi:10.2147/CMAR.S49321
    1. Weiss RB, Donehower RC, Wiernik PH, et al. Hypersensitivity reactions from taxol. J Clin Oncol. 1990;8(7):1263–1268. doi:10.1200/JCO.1990.8.7.1263
    1. Ahmad A, Sheikh S, Taran R, et al. Therapeutic efficacy of a novel nanosomal docetaxel lipid suspension compared with taxotere in locally advanced or metastatic breast cancer patients. Clin Breast Cancer. 2014;14(3):177–181. doi:10.1016/j.clbc.2013.09.011
    1. Ashraf M, Sajjad R, Khan M, et al. 156P Efficacy and safety of a novel nanosomal docetaxel lipid suspension (NDLS) as an anti cancer agent-a retrospective study. Ann Oncol. 2016;27(suppl_9). doi:10.1093/annonc/mdw579.008.
    1. Murali A, Gupta S, Pendharkar D. Efficacy and tolerability of nanoparticle docetaxel lipid suspension. J Clin Oncol. 2018;36(15_suppl):e14542–e14542. doi:10.1200/JCO.2018.36.15_suppl.e14542
    1. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–247. doi:10.1016/j.ejca.2008.10.026
    1. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Available from: . Accessed April21, 2020.
    1. National Comprehensive Cancer Network (NCCN). Breast Cancer Guidelines 2019.
    1. Cardoso F, Senkus E, Costa A, et al. 4th ESO–ESMO international consensus guidelines for advanced breast cancer (ABC 4)†. Ann Oncol. 2018;29(8):1634–1657. doi:10.1093/annonc/mdy192
    1. Ahmad A, Sheikh S, Ali SM, et al. Development of aqueous based formulation of docetaxel: safety and pharmacokinetics in patients with advanced solid tumors. J Nanomed Nanotechnol. 2015;6(3):1.
    1. Naik R, Khan MA. Doceaqualip in a patient with prostate cancer who had an allergic reaction to conventional docetaxel: a case report. Mol Clin Oncol. 2017;6(3):341–343. doi:10.3892/mco.2017.1147
    1. Prasanna R, Bunger D, Khan MA. Efficacy and safety of DoceAqualip in a patient with locally advanced cervical cancer: a case report. Mol Clin Oncol. 2018;8(2):296–299. doi:10.3892/mco.2017.1519
    1. Vyas V, Joshi N, Khan M. Novel docetaxel formulation (NDLS) in low cardiac reserve ovarian cancer. Open Access J Cancer Oncol. 2018;2(2):000122.
    1. Gupta S, Pawar SS, Bunger D. Successful downstaging of locally recurrent penile squamous cell carcinoma with neoadjuvant nanosomal docetaxel lipid suspension (NDLS) based regimen followed by curative surgery. BMJ Case Rep. 2017;2017.
    1. Rajappa S, Joshi A, Doval DC, et al. Novel formulations of docetaxel, paclitaxel and doxorubicin in the management of metastatic breast cancer. Oncol Lett. 2018;16(3):3757–3769. doi:10.3892/ol.2018.9057
    1. Spring L, Greenup R, Reynolds K, Smith BL, Moy B, Bardia A. Pathological complete response after neoadjuvant chemotherapy predicts improved survival in all major subtypes of breast cancer: systematic review and meta-analyses of over 18,000 patients. Presented at the 2016 AACR Ann Meeting. 2016. Abstract 1439.
    1. Li S, Wei W, Jiang Y, et al. Comparison of the efficacy and survival analysis of neoadjuvant chemotherapy for Her-2-positive breast cancer. Drug Des Devel Ther. 2018;12:3085–3093. doi:10.2147/DDDT.S171534
    1. Zuradelli M, Gullo G, Walshe J, et al. 446 docetaxel, carboplatin and trastuzumab (TCH) as Neoadjuvant (neoadj) therapy in patients (pts) with HER2-positive (HER2+) Operable Breast Cancer (BrCa). Eur J Cancer. 2012;48:S177. doi:10.1016/S0959-8049(12)70511-7
    1. Tiwari A, Gogia A, Deo S, et al. Retrospective study of efficacy and safety of neoadjuvant docetaxel, carboplatin, and trastuzumab in HER2-positive locally advanced and oligometastatic breast cancer: an Indian experience. Indian J Cancer. 2017;54(1):343–346. doi:10.4103/ijc.IJC_152_17
    1. Kolberg H-C, Akpolat-Basci L, Stephanou M, Hannig C, Liedtke C. Neoadjuvant chemotherapy with docetaxel, carboplatin, and weekly trastuzumab (TCH) activity in HER2-positive early breast cancer: results after a median follow-up of 4.5 years. J Clin Oncol. 2015;33(28_suppl):140. doi:10.1200/jco.2015.33.28_suppl.140
    1. Martin M. Docetaxel, doxorubicin and cyclophosphamide (the TAC regimen): an effective adjuvant treatment for operable breast cancer. Womens Health. 2006;2(4):527–537. doi:10.2217/17455057.2.4.527
    1. Jones SE, Savin MA, Holmes FA, et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006;24(34):5381–5387. doi:10.1200/JCO.2006.06.5391
    1. Jones S, Holmes FA, O’Shaughnessy J, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of us oncology research trial 9735. J Clin Oncol. 2009;27(8):1177–1183. doi:10.1200/JCO.2008.18.4028
    1. Martin M, Pienkowski T, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005;352(22):2302–2313. doi:10.1056/NEJMoa043681
    1. Jones SE, Collea R, Paul D, et al. Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, Phase 2 study. Lancet Oncol. 2013;14(11):1121–1128. doi:10.1016/S1470-2045(13)70384-X
    1. Lyseng-Williamson KA, Fenton C. Docetaxel: a review of its use in metastatic breast cancer. Drugs. 2005;65(17):2513–2531. doi:10.2165/00003495-200565170-00007
    1. Nabholtz JM, Senn HJ, Bezwoda WR, et al. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group. J Clin Oncol. 1999;17(5):1413–1424. doi:10.1200/JCO.1999.17.5.1413
    1. Chan S. Docetaxel vs doxorubicin in metastatic breast cancer resistant to alkylating chemotherapy. Oncology (Williston Park). 1997;11(8 Suppl 8):19–24.
    1. Mavroudis D, Alexopoulos A, Malamos N, et al. Salvage treatment of metastatic breast cancer with docetaxel and carboplatin. A multicenter Phase II trial. Oncology. 2003;64(3):207–212. doi:10.1159/000069306
    1. Perez EA, Suman VJ, Fitch TR, et al. A phase II trial of docetaxel and carboplatin as first-line chemotherapy for metastatic breast cancer: NCCTG study N9932. Oncology. 2005;69(2):117–121. doi:10.1159/000087813
    1. Valero V, Forbes J, Pegram MD, et al. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol. 2011;29(2):149–156. doi:10.1200/JCO.2010.28.6450
    1. Riva A, Reese D, Toppmeyer D, et al. Results of Two open-label, multicenter phase ii studies of docetaxel, platinum salts, and trastuzumab in HER2-positive advanced breast cancer. JNCI. 2004;96(10):759–769. doi:10.1093/jnci/djh133
    1. Ashraf QM, Sajad QR, Khan MA, et al. Efficacy and safety of a novel nanosomal docetaxel lipid suspension as an anticancer agent - a retrospective study. J Cancer Oncol. 2018;2(4):000132.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever