[2104] Phase II randomized adjuvant trial of dose-dense docetaxel (DOC) before or after doxorubicin/cyclophosphamide (AC) in axillary node-positive breast cancer.
Puhalla S, Young D, Ottman S, McVey A, Kendra K, Mrozek E, Rhodes C, Merriman NJ, Knapp M, Patel T, Thompson ME, Maher JF, Moore TD, Shapiro CL.. The Ohio State University, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH; Mid Ohio Oncology/Hematology, Inc., Columbus, OH; Oncology Partners Network, Cincinnati, OH; BridgeSite Clinical Research, Columbus, OH
Objective: By convention, AC is followed by taxanes in most adjuvant regimens. We hypothesized that giving DOC before AC would result in higher relative dose intensity (RDI) than the reverse sequence. To test this hypothesis, a randomized phase II trial comparing DOC
AC (Arm A) with AC DOC (Arm B) was performed. The primary objective was to calculate the RDI in each arm and compare dose reductions and delays.
Methods: Eligibility: node-positive, ECOG performance status 0 or 1, prior lumpectomy or mastectomy, no evidence of metastatic disease. Pts were randomized to receive either Arm A [DOC 75 mg/m
every 2 weeks for 4 cycles followed by AC 60mg/m, 600 mg/m every 2 weeks for 4 cycles] or Arm B [dose-dense AC followed by dose-dense DOC]. All pts received pegfilgrastim following each cycle of chemotherapy. DOC dose was reduced for neutropenic fever or any grade 3 or 4 non-hematologic toxicity; DOC was delayed for day 1 absolute neutrophil count < 1000/mm
and/or thrombocytopenia < 100,000/mm, or grade 3,4 toxicity that failed to resolve to grade 1. Pts were removed from study if toxicity did not resolve within 14 days.
Results: Between 10/04 and 6/06, a total of 56 pts have been enrolled, with 49 (88%) having completed therapy as of 4/06. In both treatment arms, the median age was 51 years (33-77 years); 46% were premenopausal; median number of positive nodes was 2 (1-35), and 69% were ER+/PR+/HER2-neu (-). The majority of toxicities were grade 1 or 2. Grade 3/4 toxicities resulting in DOC dose reductions included Arm A (per pt): headache/nausea (1), infection (1), hypersensitivity reaction (1), and hand-foot syndrome (1) and Arm B: neuropathy (3), hand-foot syndrome (2), pain (2), diarrhea (1), infection (1), and fatigue (1). The mean RDIs, dose reductions, and delays are described in the table.
Conclusions: Dose-dense DOC followed by AC is the preferred sequence as it resulted in a higher mean RDI and fewer dose reductions. If confirmed in larger studies, consideration should be given to using DOC before AC in dose-dense adjuvant therapy. Supported in part by a research grant from Sanofi-Aventis.
| Arm A (DOCAC) | Arm B (ACDOC) | p value | |
| Mean RDI (mg/m/wk) | |||
| DOC | 96% | 81% | 0.02 |
| AC | 98% | 97% | 0.48 |
| DOC dose reductions (per pt) | 4/24 (17%) | 10/25 (40%) | 0.11 |
| Dose delays (per pt) | 2/24 (8%) | 4/25 (16%) | 0.67 |
Friday, December 15, 2006 7:00 AM
Poster Session II: Treatment: Adjuvant Therapy (7:00 AM-9:00 AM)