Nanoparticle albumin-bound paclitaxel (nab-paclitaxel): extending its indications

Figures & data

Table 1. Nab-paclitaxel and neuropathy in MBC, NSCLC and Panc cancer.

Nab-paclitaxel regimen	Comparator regimen	No. of patients	Grade 3+ neuropathy	Comments	Study
260 mg/m^2 q3 weeks	Paclitaxel 175 mg/m^2 q3 weeks	229, 225	10 vs 2%	MBC: registration trial	Gradishar et al. 2005 [5]
300 mg/m^2 q3 weeks	Docetaxel 100 mg/m^2 q3 weeks	76, 74	17 vs 12%	MBC: randomized Phase II	Gradishar et al. 2009 – 2012 [11]
100 mg/m^2 q1 week	Docetaxel 100 mg/m^2 q3 weeks	76, 74	8 vs 12%	Same	Gradishar et al. 2009 – 2012 [11]
150 mg/m^2 q1 week	Docetaxel 100 mg/m^2 q3 weeks	74, 74	14 vs 12%	Same	Gradishar et al. 2009 – 2012 [11]
150 mg/m^2 q1 week + bevacizumab	Paclitaxel 90 mg/m^2 q week + bevacizumab 10 mg q2 weeks	271, 283	25 vs 16%	MBC: noninferiority Phase III	Rugo et al. 2012 [8]
100 mg/m^2 q1 week + carboplatin	Paclitaxel 200 mg/m^2 q3 weeks + carboplatin q3 weeks	521, 531	3 vs 11%	NSCLC: registrationtrial	Socinski et al. 2012 [4]
125 mg/m^2 + gemcitabine 1000 mg/m^2 q week	Gemcitabine 1000 mg/m^2 q week	431, 430	17 vs 1%	Panc: registration trial	Von Hoff et al. 2013 [12]

MBC: Metastatic breast cancer; NSCLC: Non-small-cell lung cancer; Panc: Pancreatic.

Table 2. Areas where nab-paclitaxel may offer advantages over current taxane use.

Disease	Regimen(s)	Comments and suggested trial(s)
Breast	N vs P [5,8]	See comment Table 1: N superior to P in PFS on every 3-week schedule; noninferior in weekly + bevacizumab. Could scalp cooling with N decrease alopecia? [13]
NSCLC	CarboN vs CarboP	See comment Table 1: N and P used weekly in combination with every 3-week Carbo. With better tolerance in older adults, is there a role for maintenance N?
Endometrial	CarboP [14]	Regimen has emerged as key chemotherapy backbone: N substituting for P may allow a triplet and/or weekly scheduling better
Gastric and gastroesophageal junction	DCF vs CF [15]	D increases efficacy but also substantial toxicity; triplets with N needs to be tested
Head and neck	D-> CR [16]	D increases efficacy; area for N induction?
Prostate	D; Cabazitaxel [17]	Both are approved but toxicities inhibit trials in combination with other drugs (and radiation)
Kaposi's sarcoma	P + HAART [18]	As in breast cancer, if N is effective in low weekly doses, could scalp cooling diminish alopecia? [13]
Germ cell cancer	P-containing multidrug [19]	Long-term CR: could N add to these?
Small-cell lung cancer	P triplet [20]	Timely to explore taxanes in area of few recent advances
Melanoma	P +/- Carbo or temozolomide (dacarbazine) [21,22]	Activity of P or N as single agents or in combination; could N increase effects of immunotherapy, Braf inhibitors?

C: Cisplatin; Carbo: Carboplatin; CR: Complete responses; D: Docetaxel; F: 5-Fluorouracil; N: Nab-paclitaxel; NSCLC: Non-small-cell lung cancer; P: Solvent-based paclitaxel; PFS: Progression-free survival.

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;23:7794-803

 PubMed Web of Science ®Google Scholar

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 2012;12:313-21

 PubMed Web of Science ®Google Scholar

Rugo HS, Barry WT, Moren-Aspitia A, et al. CALGB 40502/NCCTG N063H: randomized phase III trial of weekly paclitaxel, compared to weekly nanoparticle albumin bound nab-paclitaxel, or ixabepilone with or without bevacizumab as first line therapy for locally recurrent or metastatic breast cancer [abstract]. J Clin Oncol 2012;30(Suppl):abstract CRA1002

 Google Scholar

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;30:2055-62

 PubMed Web of Science ®Google Scholar

Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:1691-703

 PubMed Web of Science ®Google Scholar

Betticher DC, Delmore G, Breitenstein U, et al. Efficacy and tolerability of two scalp cooling systems for the prevention of alopecia associated with docetaxel treatment. Support Care Cancer 2013;21(9):2565-73

 PubMed Web of Science ®Google Scholar

Miller D, Fillaci V, Fleming G, et al. Randomized phase III noninferiority trial of first line chemotherapy for metastatic or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 2012;125:771-3

 Web of Science ®Google Scholar

Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 2006;24(31):4991-7

 PubMed Web of Science ®Google Scholar

Posner MR. Taxanes in cancer of head and neck. Anticancer Drugs 2014. [Epub ahead of print]

 PubMed Web of Science ®Google Scholar

Balar AV. The impact of taxanes on the management of genitourinary cancers. Anticancer Drugs 2014; Epub ahead of print

 PubMed Web of Science ®Google Scholar

Cianfrocca M, Lee S, Von Roenn J, et al. Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma: evidence of symptom palliation from chemotherapy. Cancer 2010;116(16):3969-77

 PubMed Web of Science ®Google Scholar

Einhorn LH, Abonour R, Kesler KA. Paclitaxel plus ifosfamide followed by high-dose carboplatin plus etoposide for patients with relapsed primary mediastinal nonseminomatous germ cell tumors: benefit from chemotherapy, surgery, or both? J Clin Oncol 2010;28(35):e739

 PubMed Web of Science ®Google Scholar

Jalal S, Bedano P, Einhorn L, et al. Paclitaxel plus bevacizumab in patients with chemosensitive relapsed small cell lung cancer: a safety, feasibility, and efficacy study from the Hoosier Oncology Group. J Thorac Oncol 2010;5(12):2008-11

 PubMed Web of Science ®Google Scholar