Adjuvant dose-dense doxorubicin plus cyclophosphamide followed by dose-dense nab-paclitaxel is safe in women with early-stage breast cancer: a pilot study

Abstract

Every-2-week (dose-dense) adjuvant doxorubicin (A) plus cyclophosphamide (C) followed by paclitaxel is a safe and effective adjuvant chemotherapy regimen. Every-3-week nab-paclitaxel is safe and more effective at 50% higher dose than every-3-week paclitaxel in metastatic breast cancer (BC). This study evaluated the safety of adjuvant dose-dense AC followed by dose-dense nab-paclitaxel for early-stage BC. Women with operable, histologically confirmed BC received four cycles of dose-dense A 60 mg/m(2) plus C 600 mg/m(2) with pegfilgrastim, followed by dose-dense 260 mg/m(2) nab-paclitaxel (with pegfilgrastim given as needed). Endpoints were adverse events (AEs), including myelosuppression. Patients with neuropathy were followed until symptom improvement to grade ≤ 1. Thirty women received four cycles of dose-dense AC with no unanticipated AEs, one withdrew after AC therapy. Of 29 women who began nab-paclitaxel therapy, 27 received all the four doses (mean cumulative dose, 959 mg/m(2)); one discontinued nab-paclitaxel after two doses due to unacceptable AEs. Four patients had a grade 3 nab-paclitaxel-related neuropathy (no grade 4 event). Of 29 patients, 34% received pegfilgrastim during nab-paclitaxel therapy and 31% had a nab-paclitaxel treatment delay, mainly due to hematologic toxicity. Based on the Kaplan-Meier probability estimates, the percentage of patients having ≤ 1 grade neuropathy at the end of treatment, 2, and 8 months after treatment were 59, 79, and 97%. Administering adjuvant dose-dense AC followed by 260 mg/m(2) dose-dense nab-paclitaxel was feasible in women with early-stage BC, with manageable AEs. Most patients had ≤ 1 grade neuropathy 2 months after treatment completion.

A Feasibility Study of Bevacizumab plus Dose-Dense Doxorubicin–Cyclophosphamide (AC) Followed by Nanoparticle Albumin–Bound Paclitaxel in Early-Stage Breast Cancer

“…In addition, the administration of nab-paclitaxel every second week may offer an efficacy advantage over administration every third week (29). Previous studies demonstrated the safety of substituting nab-paclitaxel for conventional paclitaxel in the dose-dense adjuvant regimen (30, 31). To inform subsequent and ongoing clinical trials, we built on these observations by testing the cardiac safety and tolerability of bevacizumab added to adjuvant dose-dense doxorubicin–cyclophosphamide followed by nab-paclitaxel and incorporated studies of potential predictors of HTN and CHF.…”

Clinical Experience with Nanoparticle Albumin Bound (Nab) Paclitaxel (Abraxane®)

“…26 Women with high risk breast cancer (T 1-3 N 1-2 , or T 2 N 0 disease) were enrolled to receive four cycles of dose-dense A (60 mg/m 2 ) plus C (600 mg/m 2 ) with peg-filgrastim, followed by dose-dense nab-paclitaxel (260 mg/m 2 ) with peg-filgrastim given as needed. 30 patients received four cycles of dose-dense AC and 29 women proceeded to nab-paclitaxel therapy.…”

The mesenchymal tumor microenvironment

“…137 To this end, the combination of adjuvant dosedense doxorubicin plus cyclophosphamide followed by dosedense nab-paclitaxel was recently found to be safe for use in women with early-stage breast cancer. 138 Interestingly, it has also been suggested that SPARC may be a stromal tumor suppressor protein which conveys resistance to therapies. In fact, a recent work demonstrated that a peptide analogous to SPARC has tumor-regressing and chemo-sensitizing activities in vitro and in pre-clinical animal models.…”

“…Breast cancer models and clinical trials 131,132,137,138 Prostate cancer clinical trial 133 Pancreatic cancer clinical trial 134 Note that additional (not listed) reagents may be available. The relevant targets, therapeutic agents and models used are provided.…”