Pilot Investigation of Ultrasound Imaging and Spectroscopy as Early Indicators of Locally- Advanced Breast Cancer Response to Neoadjuvant Treatment

10515 Background: A phase II clinical trial was conducted to study the safety and efficacy of neoadjuvant docetaxel/carboplatin (T/C) with or without trastuzumab (H) in women with stage III breast cancer. Methods: Forty-eight of 75 planned primary breast cancer patients (T3 or T4, any N, M0), age between 18 and 80 have been enrolled. Four cycles of T (75 mg/m2) + C (AUC 6) were given every 3 weeks preoperatively. Patients with HER-2 amplified tumors (FISH +) were randomized to receive either weekly concurrent H or T/C alone preoperatively and T/C plus H postoperatively. Tumors were assessed clinically at baseline and after neoadjuvant therapy. Cardiac assessment consisted of medical history, EKG and LVEF (by echocardiogram or MUGA) at baseline and at the end of neoadjuvant chemotherapy. Results: Available data from 45 of 48 enrolled patients showed 49% (22 cases) with complete clinical response, with 54.5% being HER-2 (+) (12 cases). Stable disease was seen in one patient who was HER-2 (−) (2.2%). Of 37 with complete pathology verification, 11 (29.7%) showed pathologic complete response (pCR) of the primary tumor with 5 cases being HER-2 (+). Of the 22 HER-2 (+) cases that completed neoadjuvant treatment, 11 received T/C/H and 11 received T/C. pCR was noted in 36.4% of the T/C/H group and 9% of the T/C group. LVEF data is available from 43 patients during the neoadjuvant phase, showing 18.6% (8 cases) with decrease of ≥ 10% (5 patients in the T/C arm and 3 patients in the T/C/H arm), although none had cardiac symptoms or LVEF below the normal limit. Conclusions: T/C ± H is clinically active in patients with locally advanced breast cancer including a 30% pCR rate. The cardiotoxicity rates were comparable between patients who received T/C and T/C/H. No significant financial relationships to disclose.

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A phase II study of gemcitabine (G), peghilated liposomal doxorubicin (PLD) and docetaxel (D) in locally advanced breast cancer (LABC): An interim analysis

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10789 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10789-10789

Author(s):

G. Artioli ◽

F. Bozza ◽

G. Cartei ◽

S. Zovato ◽

R. Mencarelli ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Interim Analysis ◽

Tumor Response ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Advanced Breast ◽

Residual Tumour ◽

Response To Chemotherapy

10789 Background: On the basis of general and our own experience neoadjuvant therapy is justified in patients with locally advanced breast cancer to reduce cancer and to perform a conservative surgery. In this study we evaluated the efficacy of G plus D and PLD as first-line therapy in LABC. Methods: To date sixteen consecutive patients with LABC have been enrolled into the study. All patients before neoadjuvant treatment, underwent biopsy for hormonal receptors and c-erb-B2 assessment. Patients received G 1250 mg/m2 on day 1 and G 1000 mg/m2, T 75 mg/m2 and D 25–30 mg/m2 on day 8 (escalation dose was 25 mg/m2 at first cycle, 27.5 mg/m2 at second cycle and 30 mg/m2 at third cycle), every 21 days with G-CSF support on day 3, 10, 12 and 14. Tumor response was evaluated on the basis of surgeon consultation and breast MRI after 4 cycles. If tumor response was higher than 50% patients underwent 2 more cycles; if it was 50% ore less or because of unacceptable toxicity they underwent surgery after 4 cycles. Microscopic assessment of the extent and type of residual tumour was made. Results: 16 patients were enrolled comprehensive of 2 with no symptomatic bone metastases. Median age was 50 years-old, and 100% had a WHO performance status (PS) of 0 and EORTC QoL was submitted. Four patients were submitted to surgery after 4 cycles, one after 5 cycles of CT with 5 pPR more than 50%. Three patients had a pathological complete response, 2 partial response more than 50% and 1 stable disease after 6 cycles. (a total of 70% of pPR, 30% of pRC, 10% of pSD). Five patients are still on treatment. One patient died because of acute respiratory distress syndrome. Major toxicity was mucositis G3–4 in one patient. PPE was G3–4 in 3 patients, one discontinued chemotherapy with PLD and continued with Epirubicin. 2 patients received Epirubicin after the first cycle of PLG because of acute allergic reaction. Conclusions: This regimen of chemotherapy seems feasible and active in LABC. At the interim analysis results it has been noted that the best response to chemotherapy was among patients having worse prognostic factors (histology and staging). No significant financial relationships to disclose.

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Toxicity results and early outcome data on a randomized phase II study of docetaxel ± bevacizumab for locally advanced, unresectable breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.3049 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 3049-3049 ◽

Cited By ~ 7

Author(s):

J. A. Lyons ◽

P. Silverman ◽

S. Remick ◽

H. Chen ◽

R. Leeming ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Neoadjuvant Therapy ◽

Phase Ii ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Advanced Breast ◽

Colon Perforation ◽

Randomized Phase Ii

3049 Background: Preclinical models of combination angiogenesis inhibitor bevacizumab (rhuMAbVEGF) and docetaxel demonstrate synergistic suppression of capillary vessel formation. Based upon these data, we developed a randomized phase II trial in order to evaluate the vascular effects on tumor regression with combination bevacizumab/docetaxel vs. docetaxel in the treatment of locally advanced breast cancer. Methods: 49 patients (pts) were randomized to receive neoadjuvant therapy with bevacizumab (10 mg/kg qowk) and docetaxel (two 8-week cycles of 35 mg/m2 weekly x 6 with a 2 wk break) (BD=24) or docetaxel (D=25) alone. Eligible pts had locally unresectable breast cancer with (n=6) or without distant metastasis (n=43); 16 patients presented with inflammatory breast cancer. Pts whose disease responded, sequentially underwent definitive surgery (4 weeks after BD or D), radiation, 4 cycles of conventional Adriamycin/cyclophosphamide, and tamoxifen or anastrazole (if ER/PR+). Results: Among the 49 pts: 7 clinical CRs, 32 PRs, 5 NR, and 5 PD. Of the 37 pts who underwent surgery: the median number of pathologically positive lymph nodes (LN) was 1 (BD=6, D=1; p=0.228); range 0–20; 43% were LN negative. Neoadjuvant treatment toxicity for both arms was acceptable with no significant differences between the two arms. Grade 4 toxicity included BD - new papillary thyroid cancer (1), neutropenia (1), hyperuricemia (1) and colon perforation (1); and D: - hyperglycemia (1) and hyperuricemia (1). 21 patients in each arm experienced a grade 3 toxicity. There were no episodes of uncontrolled hypertension, proteinuria, or thrombosis. Delayed wound healing (unable to start radiation w/in 6 weeks of surgery) occurred in 8 pts: BD=5; D=3 (p=0.691). Only 1 pt (D) experienced a change in LVEF by > 15% or below the institution’s lower limit of normal. Conclusions: Neoadjuvant therapy for locally advanced breast cancer using docetaxel with bevacizumab is well tolerated. Further studies are required to determine the added efficacy from bevacizumab. Correlative studies on impact of treatment on angiogenesis will be reported separately. (Sponsored by grants: K23CA 87725–01, M01 RR 00080, UO1 CA 62502, 5P30 CA43703-NCI/AVON, Aventis) No significant financial relationships to disclose.

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