| General information |
| Database: | DB01032 |
| Objective: | Dosedense doxorubicin and cyclophosphamide followed by dosedense albuminbound paclitaxel plus bevacizumab is safe as adjuvant therapy in patients with early stage breast cancer |
| Authors: | John Pippen |
| Title: | Dosedense doxorubicin and cyclophosphamide followed by dosedense albuminbound paclitaxel plus bevacizumab is safe as adjuvant therapy in patients with early stage breast cancer. |
| Journal: | Breast Cancer Research and Treatment |
| Year: | 2011 |
| PMID: | 21976055 |
| Trial Design |
| Clinical Trial Id: | NCT00394251 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | doxorubicin and cyclophosphamide followed by dosedense albuminbound paclitaxel plus bevacizumab |
| Study Type: | This openlabel, multicenter, randomizedphase II safety study was designed to compare the safety and tolerability of dosedense (everyIIweek) AC ¡ú albuminbound paclitaxel plus bevacizumab with dosedense AC ¡ú cremophorformulated paclitaxel plus bevacizumab therapy in womenwith early stage breast cancer. Specifically, the goal of this study was to determine whether the AC ¡ú albuminbound paclitaxel armwould achieve an equal safety profile to the AC ¡ú cremophorformulated paclitaxel arm despite the substantially higher planned dose of paclitaxel in the AC ¡ú albuminbound paclitaxel arm. |
| Key Patients Feature: | more than and equal to 18 to less than and equal to 70yearsold women with operable, histologically confirmed adenocarcinoma of the breast (defined as tumors that are T13, N13, or nodenegative [N0] disease with tumors that are>2 cm, or N0 disease with tumors that are >1 cm and estrogen and progesteronereceptor negative). patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1. Patients with human epidermal growth factor receptor 2positive breast cancer who were eligible for adjuvant trastuzumab therapy or with stage IV metastatic disease were not eligible in this study. patients were also excluded if they received prior neoadjuvant therapy for the present disease or any prior anthracycline or taxane therapy. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | AC ¡ú cremophorformulated paclitaxel arm |
| Treatment Info: | 4 cycles of dosedense A 60 mg/m2 plus C 600 mg/m2 IV with SC pegfilgrastim, followed by 4 cycles of either dosedense IV abP 260 mg/m2 or cfP 175 mg/m2. Bevacizumab was given during and following chemotherapy. |
| Primary End Point: | the incidence of treatmentrelated adverse events (AEs) at 3 and 6 months following the completion of chemotherapy. |
| Secondary End Point: | cumulative dose of chemotherapy delivered (mg/m2), average dose intensity (mg/m2/week), and the incidence of patients experiencing dose modifications, dose interruptions, and premature discontinuation of study drug. |
| Patients Number: | 197 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequently reported treatmentrelated AEs (all grades) during the entire regimen were fatigue (85 and 77% in the AC ¡ú albuminbound paclitaxel and the AC ¡ú cremophorformulated paclitaxel arm, respectively), sensory neuropathy (82%, 74%), leukopenia (79%, 77%), anemia (79%, 68%), nausea (78%, 79%), and alopecia (63%, 67%). In general, peripheral neuropathy emerged more frequently during taxane therapy than during AC therapy. |
| Conclusions: | In this study in women with earlystage breast cancer, administration of adjuvant dosedense (i.e., every2week) AC therapy with pegfilgrastim followed by dosedense albuminbound paclitaxel plus bevacizumab was feasible and produced a manageable safety profile. This study was not designed to examine efficacy endpoints, hotheyver, higher paclitaxel delivery, as seen in the albuminbound paclitaxel arm, may potentially lead to higher efficacy. Prospective studies with overall response endpoints would be required to anstheyr directly whether the promising cumulative dose and safety results from this novel combination of dosedense AC therapy followed by dosedense albuminbound paclitaxel and bevacizumab will translate to higher antitumor activity in early breast cancer patients. |