A dual-center randomized controlled double blind trial assessing the effect of acupuncture in reducing musculoskeletal symptoms in breast cancer patients taking aromatase inhibitors.

Up to 50 % of women receiving aromatase inhibitor (AI) complain of AI-associated musculoskeletal symptoms (AIMSS) and 15 % discontinue treatment. We conducted a randomized, sham-controlled trial to evaluate whether acupuncture improves AIMSS and to explore potential mechanisms. Postmenopausal women with early stage breast cancer, experiencing AIMSS were randomized to eight weekly real or sham acupuncture sessions. We evaluated changes in the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain visual analog scale (VAS) following the intervention compared to baseline. Serum estradiol, ß-endorphin, and proinflammatory cytokine concentrations were measured pre and post-intervention. We enrolled 51 women of whom 47 were evaluable, including 23 randomized to real and 24 to sham acupuncture. Baseline characteristics were balanced between groups with the exception of a higher HAQ-DI score in the real acupuncture group (p = 0.047). We did not observe a statistically significant difference in reduction of HAQ-DI (p = 0.30) or VAS (p = 0.31) between the two groups. Following eight weekly treatments, we observed a statistically significant reduction of IL-17 (p ≤ 0.009) in both groups. No significant modulation was seen in estradiol, ß-endorphin, or other proinflammatory cytokine concentrations in either group. We did not observe a significant difference in AIMSS changes between real and sham acupuncture. As sham acupuncture used in this study may not be equivalent to placebo, further studies with a non-acupuncture arm may be required to establish whether acupuncture is beneficial for the treatment of AIMSS.

A phase I toxicity and feasibility trial of sequential dose-dense induction chemotherapy with doxorubicin, paclitaxel, and 5-fluorouracil followed by high dose consolidation for high-risk primary breast cancer.

PURPOSE: We studied sequential dose-dense doxorubicin, paclitaxel, and 5-fluorouracil (A-T-F) before high dose chemotherapy (HDC) with autologous peripheral blood stem cell support (PBSCT). Our aims were to determine the maximum tolerated dose (MTD) of 5-FU in the dose-dense regimen and to determine the impact of dose-dense chemotherapy on HDC/PBSCT. METHODS: Patients with Stage IIIB or Stage II or IIIA breast cancer with > or = 4 involved ipsilateral lymph nodes were treated with nine cycles of chemotherapy at 14-day intervals. The regimen was doxorubicin at 80 mg/m2 x 3, followed by paclitaxel at 140 mg/m2 over 96 h x 3, then 5-FU at doses of 1285, 1470, or 1655 mg/m2 by continuous intravenous infusion over 72 h x 3. Patients then underwent a G-CSF-stimulated peripheral blood stem cell (PBSC) apheresis prior to receiving HDC with autologous PBSCT. RESULTS: We identified 1285 mg/m2 as the MTD of 5-FU in this regimen. 5-FU-related DLTs included hand-foot syndrome, mucositis, and facial edema with somnolence. Unexpectedly, 3/19 treated patients developed congestive heart failure that prevented planned HDC. Compared to standard dose doxorubicin-containing adjuvant therapy, the dose-dense regimen also decreased CD34+ PBSC yields by about 40% (p = 0.049), requiring that 50% of patients have a supplemental bone marrow harvest. There was no difference in time to neutrophil, platelet, and red blood cell recovery after HDC. CONCLUSIONS: This regimen resulted in an unacceptably high rate of cardiac toxicity and is not recommended for further testing. It may be feasible to use a different schedule of 5-FU-containing dose-dense chemotherapy, particularly for the induction therapy of high-risk primary breast cancer prior to novel targeted therapies.