Incidence and risk of peripheral neuropathy with nab‐paclitaxel in patients with cancer: a meta‐analysis

&NA; Nab‐paclitaxel, a Cremophor EL‐free formulation of paclitaxel, is used to treat various malignancies. Peripheral neuropathy is one of its major toxicities, although the overall incidence remains unclear. We performed a meta‐analysis to calculate the incidence of peripheral neuropathy in cancer patients treated with nab‐paclitaxel and to compare the relative risk (RR) with conventional taxanes. The electronic databases were searched for relevant clinical trials. Eligible studies included phase II and III prospective clinical trials of cancer patients treated with nab‐paclitaxel with toxicity profile on peripheral neuropathy. Statistical analyses were done to calculate summary incidences, RRs and 95% confidence intervals (CI), using fixed‐effects or random‐effects models based on the heterogeneity of the included studies. Nineteen trials were selected for the meta‐analysis, yielding a total of 2878 cancer patients. The overall incidences of peripheral neuropathy (all‐grade) was 51.0% (95% CI: 45.1‐57.6%), and that of high‐grade peripheral neuropathy was 12.4% (9.8‐15.7%). The RRs of peripheral neuropathy of nab‐paclitaxel compared to taxanes were not increased for all‐grade and high‐grade peripheral neuropathy. Nab‐paclitaxel is associated with an increased risk of developing peripheral neuropathy. Future clinical studies are still needed to investigate the risk reduction and possible use of nab‐paclitaxel.

[1]  T. Choueiri,et al.  Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  L. Deangelis,et al.  Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing , 1997, Journal of Neuro-Oncology.

[3]  A. Eisen,et al.  Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study. , 2013, The Lancet. Oncology.

[4]  T. Kolevska,et al.  Phase II trial of nab-paclitaxel as first-line therapy of hormone refractory metastatic prostate cancer (HRPC). , 2009, Journal of Clinical Oncology.

[5]  A. Tsao.  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 , 2012 .

[6]  Cristina Saura,et al.  Nanoparticle albumin-bound (nab™)-paclitaxel: improving efficacy and tolerability by targeted drug delivery in metastatic breast cancer , 2010 .

[7]  A. Valachis,et al.  Overall survival benefit for weekly vs. three-weekly taxanes regimens in advanced breast cancer: A meta-analysis. , 2010, Cancer treatment reviews.

[8]  K. Muro,et al.  ABI-007 in the treatment of unresectable or recurrent gastric cancer refractory to fluoropyrimidine-containing regimen: Updated data from the multicenter phase II study. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  M. Kris,et al.  Phase I/II trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell lung cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  C. Begg,et al.  Operating characteristics of a rank correlation test for publication bias. , 1994, Biometrics.

[11]  Terry L. Smith,et al.  Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  I. Reis,et al.  A Phase II Trial of nab-Paclitaxel as Second-line Therapy in Patients With Advanced Pancreatic Cancer , 2013, American journal of clinical oncology.

[13]  M. Sereno,et al.  Chemotherapy-induced peripheral neuropathy: clinical features, diagnosis, prevention and treatment strategies , 2010, Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico.

[14]  A. Ribas,et al.  A phase 2 clinical trial of nab‐paclitaxel in previously treated and chemotherapy‐naive patients with metastatic melanoma , 2009, Cancer.

[15]  P. Soon-Shiong,et al.  SPARC Expression Correlates with Tumor Response to Albumin-Bound Paclitaxel in Head and Neck Cancer Patients. , 2009, Translational oncology.

[16]  M. Shahin,et al.  A phase II evaluation of nanoparticle, albumin-bound (nab) paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer: a Gynecologic Oncology Group study. , 2011, Gynecologic oncology.

[17]  A. Eschalier,et al.  Chemotherapy-induced peripheral neuropathies: from clinical relevance to preclinical evidence , 2011, Expert opinion on drug safety.

[18]  C. Sima,et al.  A phase 2 study of weekly albumin-bound paclitaxel (Abraxane®) given as a two-hour infusion , 2011, Cancer Chemotherapy and Pharmacology.

[19]  R. Peto,et al.  Beta blockade during and after myocardial infarction: an overview of the randomized trials. , 1985, Progress in cardiovascular diseases.

[20]  E. Winer,et al.  CALGB 40502/NCCTG N063H: Randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-paclitaxel (NP) or ixabepilone (Ix) with or without bevacizumab (B) as first-line therapy for locally recurrent or metastatic breast cancer (MBC). , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  L. Asmar,et al.  Phase II evaluation of nanoparticle albumin-bound paclitaxel in platinum-sensitive patients with recurrent ovarian, peritoneal, or fallopian tube cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  C. Magi-Galluzzi,et al.  Phase II trial of neoadjuvant nab-paclitaxel in high risk patients with prostate cancer undergoing radical prostatectomy. , 2009, The Journal of urology.

[23]  J B Vermorken,et al.  A multicentre, randomised phase II study of weekly or 3-weekly docetaxel in patients with metastatic breast cancer. , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[24]  D. Lake,et al.  Phase II trial of weekly nanoparticle albumin-bound paclitaxel with carboplatin and trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer. , 2010, Clinical breast cancer.

[25]  Patrick Soon-Shiong,et al.  Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[26]  Michael Hawkins,et al.  Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  W. Gradishar,et al.  Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  J. Thigpen.  A Phase 2 Clinical Trial of nab-Paclitaxel in Previously Treated and Chemotherapy-Naive Patients With Metastatic Melanoma , 2010 .

[29]  J. Thigpen.  Phase II Evaluation of Nanoparticle Albumin–Bound Paclitaxel in Platinum-Sensitive Patients With Recurrent Ovarian, Peritoneal, or Fallopian Tube Cancer , 2009 .

[30]  N. Robert,et al.  Phase II study of weekly albumin-bound paclitaxel for patients with metastatic breast cancer heavily pretreated with taxanes. , 2007, Clinical breast cancer.

[31]  K. Muro,et al.  Phase II trial of nanoparticle albumin-bound paclitaxel as second-line chemotherapy for unresectable or recurrent gastric cancer , 2014, Cancer science.

[32]  G. Hortobagyi,et al.  Phase 3 study comparing the use of docetaxel on an every‐3‐week versus weekly schedule in the treatment of metastatic breast cancer , 2008, Cancer.

[33]  T. Cosgriff,et al.  A phase II study of weekly nanoparticle albumin-bound paclitaxel with or without trastuzumab in metastatic breast cancer. , 2011, Clinical breast cancer.

[34]  T. Campbell,et al.  Comparison of weekly versus every 3 weeks paclitaxel in the treatment of advanced solid tumors: a meta-analysis. , 2012, Cancer treatment reviews.

[35]  M J Hawkins,et al.  Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[36]  J. Slingerland,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 , 2010, Breast Cancer Research and Treatment.

[37]  Deborah Ashby,et al.  Adjusting for publication bias: modelling the selection process. , 2004, Journal of evaluation in clinical practice.

[38]  Sudhakar Tummala,et al.  NCCN task force report: management of neuropathy in cancer. , 2009, Journal of the National Comprehensive Cancer Network : JNCCN.

[39]  Anup V. Desai,et al.  Does sleep deprivation worsen mild obstructive sleep apnea? , 2003, Sleep.

[40]  John P A Ioannidis,et al.  Heterogeneity testing in meta‐analysis of genome searches , 2005, Genetic epidemiology.

[41]  Wolfgang Grisold,et al.  Chemotherapy‐induced neuropathy , 2008, Journal of the peripheral nervous system : JPNS.

[42]  Brian Samuels,et al.  Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  D. Alberts,et al.  Phase II trial of nab-paclitaxel in the treatment of recurrent or persistent advanced cervix cancer: A gynecologic oncology group study. , 2012, Gynecologic oncology.