Aim: To investigate the toxicity of nab-paclitaxel (wNP)/nonpegylated liposome-encapsulated doxorubicin (wNPLD) combination in HER2-negative metastatic breast cancer (MBC) patients as first-line treatment. Materials & methods: Phase I, single-arm study in metastatic breast cancer patients naive to previous chemotherapy for advanced disease. A 3 + 3 dose-escalation design was used to determine the safety. Primary endpoints were the identification of dose-limiting toxicity and maximum tolerated dose. Results: In total, 12 patients (mean age: 52 years; median metastatic sites: 2) were enrolled and 97 cycles were completed. Maximum tolerated dose was wNP + wNPLD 25 mg/m². The most common adverse events were neutropenia, nausea, diarrhea and mucositis. The objective response rate was 68% (response mean duration: 12.6 months). Conclusion: wNP/wNPLD combination constitutes an active regimen with mild toxicity.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Winer EP, Morrow M, Osborne CK, Harris JR Cancer of the breast: Malignant tumors of the breast. Cancer: Principles and Practice of Oncology 6th edition (July 2001). Devita VTHellman SRosenberg SA (Eds). Lippincott Williams & Wilkins, PA, USA, 1401–1446 (2011).
Google Scholar
2. Fabi A, Giannarelli D, Malaguti P et al. Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer: clinical results and biological observations in taxane-pretreated patients. Drug Design Develop. Ther. 9, 6177–6183 (2015). • Reports the safety profile of nab-paclitaxel together with its antitumor activity when used as a single treatment after patient pretreatment with taxanes. It represents the starting point from which the current investigation has developed.
Medline CASGoogle Scholar
3. 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. 23, 7794–7803 (2005). •• This is an important Phase III trial assessing the lower toxicity profile of the first biologically interactive albumin-bound paclitaxel in a nanometer particle free of solvents, in patients with metastatic breast cancer (BC). The lower incidence of myelosuppression and the low grade of hypersensitivity reactions reported with comparison with the standard vehicles of delivery, encourages the use of the new formulations.
Medline CASGoogle Scholar
4. Winer EP, Berry DA, Woolf S et al. Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: Cancer and Leukemia Group B Trial 9342. J. Clin. Oncol. 22, 2061–2068 (2004).
Medline CASGoogle Scholar
5. Lee JJ, Saiful Yazan L, Che Abdullah CA. A review on current nanomaterials and their drug conjugate for targeted breast cancer treatment. Int. J. Nanomedicine 12, 2373–2384 (2017).
Medline CASGoogle Scholar
6. Lao J, Madani J, Puértolas T et al. Liposomal doxorubicin in the treatment of breast cancer patients: a review. J. Drug Deliv. 2013, 456409 (2013). •• This review extensively reports the state of the art of the use of doxorubicin delivered by liposomes in both metastatic and early BC therapy.
MedlineGoogle Scholar
7. Yardley DA, Brufsky A, Coleman RE et al. Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tenacity study): study protocol for a randomized controlled trial. Trials 16, 575 (2015).
MedlineGoogle Scholar
8. Schettini F, Giuliano M, De Placido S, Arpino G. Nab-paclitaxel for the treatment of triple-negative breast cancer: rationale, clinical data and future perspectives. Cancer Treat. Rev. 50, 129–141 (2016).
Medline CASGoogle Scholar
9. Gradishar WJ, Krasnojon D, Cheporov S et al. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first line therapy for metastatic breast cancer. J. Clin. Oncol. 27, 3611–3619 (2009).
Medline CASGoogle Scholar
10. Gradishar WJ, Krasnojon D, Cheporov S et al. Phase II trial of nab-paclitaxel compared with docetaxel as first-line chemotherapy in patients with metastatic breast cancer: final analysis of overall survival. Clin. Breast Cancer 12, 313–321 (2012).
Medline CASGoogle Scholar
11. Blum JL, Savin MA, Edelman G et al. Phase II study of weekly albumin-bound paclitaxel for patients with metastatic breast cancer heavily pretreated with taxanes. Clin. Breast Cancer 7, 850–856 (2007).
Medline CASGoogle Scholar
12. Ibrahim NK, Samuels B, Page R et al. Multicenter Phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. J. Clin. Oncol. 23, 6019–6026 (2005).
Medline CASGoogle Scholar
13. Hamilton E, Kimmick G, Hopkins J et al. Nab-paclitaxel/bevacizumab/carboplatin chemotherapy in first-line triple negative metastatic breast cancer. Clin. Breast Cancer 13, 416–420 (2013).
Medline CASGoogle Scholar
14. Lobo C, Lopes G, Baez O et al. Final results of a Phase II study of nab-paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer. Breast Cancer Res. Treat. 123, 427–435 (2010).
Medline CASGoogle Scholar
15. Rosati M, Raimondi C, Baciarello G et al. Weekly combination of non-pegylated liposomal doxorubicin and taxane in first-line breast cancer: wALt trial (Phase I–II). Ann. Oncol. 22, 315–320 (2011).
Medline CASGoogle Scholar
16. Werner TL, Ray A, Lamb JG et al. A Phase 1 study of neoadjuvant chemotherapy with nab-paclitaxel, doxorubicin and cyclophosphamide in patients with stage II–III breast cancer. Clin. Breast Cancer 17, 503–509 (2017).
Medline CASGoogle Scholar
17. Fabi A, Mirri A, Felici A et al. Fixed dose-rate gemcitabine as radiosensitizer for newly diagnosed glioblastoma: a dose-finding study. J. Neurooncol. 87(1), 79–84 (2008).
Medline CASGoogle Scholar
18. Pernas S, Martin M, Kaufman PA et al. Balixafortide plus eribulin in HER2-negative metastatic breast cancer: a Phase 1, single-arm, dose-escalation trial. Lancet Oncol. 19(6), 812–824 (2018).
MedlineGoogle Scholar
19. Eisenhauer EA, Therasse P, Bogaerts J et al. New response evaluation criteria in solid tumors. Revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228–247 (2009).
Medline CASGoogle Scholar
20. Lluch A, Alvarez I, Muñoz M, Seguí MÁ, Tusquets I, García-Estévez L. Treatment innovations for metastatic breast cancer: nanoparticle albumin-bound (NAB) technology targeted to tumors. Crit. Rev. Oncol. Hematol. 89, 62–72 (2014). • Recent review that analyses the trials in which the use of nanoparticle albumin-bound paclitaxel resulted in superior efficacy compared with standard cytotoxic drugs, underlying the nab-paclitaxel as a promising treatment of metastatic BC.
MedlineGoogle Scholar
21. Nisticò C, Bria E, Cuppone F et al. Weekly epirubicin and paclitaxel with granulocyte colony-stimulating factor support in previously untreated metastatic breast cancer patients. Anticancer Drugs 18, 687–692 (2007).
Medline CASGoogle Scholar
22. 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 non-hematologic malignancies. J. Clin. Oncol. 23, 7785–7793 (2005).
Medline CASGoogle Scholar

Vol. 16, No. 22

Metrics

Downloaded 135 times

History

Received 2 March 2020

Accepted 20 May 2020

Published online 5 June 2020

Published in print August 2020

Information

Keywords

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Editorial assistance was provided by Chiara Degirolamo, Aashni Shah, Barabara Bartolini and Luca Giacomelli (Polistudium srl, Milan, Italy). This assistance was supported by internal funds.

Ethical conduct of research

The authors state that the experiments comply with the current Italian laws. In addition, the local Ethical Committee has approved the study protocol, and all patients signed an informed consent before inclusion.

PDF download