Weekly paclitaxel and concurrent pazopanib following doxorubicin and cyclophosphamide as neoadjuvant therapy for HER-negative locally advanced breast cancer: NSABP Foundation FB-6, a phase II study. []
Weekly paclitaxel and concurrent pazopanib following doxorubicin and cyclophosphamide as neoadjuvant therapy for HER-negative locally advanced breast cancer: NSABP Foundation FB-6, a phase II study. []
- 2015
This multicenter single-arm phase II study evaluated the addition of pazopanib to concurrent weekly paclitaxel following doxorubicin and cyclophosphamide as neoadjuvant therapy in human epidermal growth factor receptor (HER2)-negative locally advanced breast cancer (LABC). Patients with HER2-negative stage III breast cancer were treated with doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) for four cycles every 3 weeks followed by weekly paclitaxel 80 mg/m(2) on days 1, 8, and 15 every 28 days for four cycles concurrently with pazopanib 800 mg orally daily prior to surgery. Post-operatively, pazopanib was given daily for 6 months. The primary endpoint was pathologic complete response (pCR) in the breast and lymph nodes. Between July 2009 and March 2011, 101 patients with stage IIIA-C HER2-negative breast cancer were enrolled. The pCR rate in evaluable patients who initiated paclitaxel and pazopanib was 17 % (16/93). The pCR rate was 9 % (6/67) in hormone receptor-positive tumors and 38 % (10/26) in triple-negative tumors. Pre-operative pazopanib was completed in only 39 % of patients. The most frequent grade 3 and 4 adverse events during paclitaxel and pazopanib were neutropenia (27 %), diarrhea (5 %), ALT and AST elevations (each 5 %), and hypertension (5 %). Although the pCR rate of paclitaxel and pazopanib following AC chemotherapy given as neoadjuvant therapy in women with LABC met the pre-specified criteria for activity, there was substantial toxicity, which led to a high discontinuation rate of pazopanib. The combination does not appear to warrant further evaluation in the neoadjuvant setting for breast cancer.
0167-6806
*Breast Neoplasms/dt [Drug Therapy]
*Cyclophosphamide/ad [Administration & Dosage]
*Doxorubicin/ad [Administration & Dosage]
*Paclitaxel/ad [Administration & Dosage]
*Pyrimidines/ad [Administration & Dosage]
*Sulfonamides/ad [Administration & Dosage]
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms/pa [Pathology]
Cyclophosphamide/ae [Adverse Effects]
Doxorubicin/ae [Adverse Effects]
Drug-Related Side Effects and Adverse Reactions
Female
Fluorouracil/ad [Administration & Dosage]
Humans
Lymph Nodes/de [Drug Effects]
Middle Aged
Neoadjuvant Therapy
Neoplasm Staging
Paclitaxel/ae [Adverse Effects]
Pyrimidines/ae [Adverse Effects]
Receptor, ErbB-2/ge [Genetics]
Sulfonamides/ae [Adverse Effects]
Washington Cancer Institute
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
This multicenter single-arm phase II study evaluated the addition of pazopanib to concurrent weekly paclitaxel following doxorubicin and cyclophosphamide as neoadjuvant therapy in human epidermal growth factor receptor (HER2)-negative locally advanced breast cancer (LABC). Patients with HER2-negative stage III breast cancer were treated with doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) for four cycles every 3 weeks followed by weekly paclitaxel 80 mg/m(2) on days 1, 8, and 15 every 28 days for four cycles concurrently with pazopanib 800 mg orally daily prior to surgery. Post-operatively, pazopanib was given daily for 6 months. The primary endpoint was pathologic complete response (pCR) in the breast and lymph nodes. Between July 2009 and March 2011, 101 patients with stage IIIA-C HER2-negative breast cancer were enrolled. The pCR rate in evaluable patients who initiated paclitaxel and pazopanib was 17 % (16/93). The pCR rate was 9 % (6/67) in hormone receptor-positive tumors and 38 % (10/26) in triple-negative tumors. Pre-operative pazopanib was completed in only 39 % of patients. The most frequent grade 3 and 4 adverse events during paclitaxel and pazopanib were neutropenia (27 %), diarrhea (5 %), ALT and AST elevations (each 5 %), and hypertension (5 %). Although the pCR rate of paclitaxel and pazopanib following AC chemotherapy given as neoadjuvant therapy in women with LABC met the pre-specified criteria for activity, there was substantial toxicity, which led to a high discontinuation rate of pazopanib. The combination does not appear to warrant further evaluation in the neoadjuvant setting for breast cancer.
0167-6806
*Breast Neoplasms/dt [Drug Therapy]
*Cyclophosphamide/ad [Administration & Dosage]
*Doxorubicin/ad [Administration & Dosage]
*Paclitaxel/ad [Administration & Dosage]
*Pyrimidines/ad [Administration & Dosage]
*Sulfonamides/ad [Administration & Dosage]
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms/pa [Pathology]
Cyclophosphamide/ae [Adverse Effects]
Doxorubicin/ae [Adverse Effects]
Drug-Related Side Effects and Adverse Reactions
Female
Fluorouracil/ad [Administration & Dosage]
Humans
Lymph Nodes/de [Drug Effects]
Middle Aged
Neoadjuvant Therapy
Neoplasm Staging
Paclitaxel/ae [Adverse Effects]
Pyrimidines/ae [Adverse Effects]
Receptor, ErbB-2/ge [Genetics]
Sulfonamides/ae [Adverse Effects]
Washington Cancer Institute
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't