Radiosensitization of Chemotherapy-Refractory, Locally Advanced or Locally Recurrent Breast Cancer With Trastuzumab: A Phase II Trial

Journal Article · Mon Mar 15 04:00:00 EDT 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2009.03.027· OSTI ID:21372152

Halle, Jan ^[1]; Ferraro, Madlyn ^[2]; Carey, Lisa ^[3]; Moore, Dominic T ^[2]; Ollila, David ^[4]; Sartor, Carolyn I ^[1]

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1. Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC (United States)
2. Lineberger Comprehensive Cancer Center, Chapel Hill, NC (United States)
3. Department of Internal Medicine, Division of Hematology and Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC (United States)
4. Department of Surgery, Division of Surgical Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC (United States)

Purpose: Trastuzumab (Herceptin), an anti-human epidermal growth factor receptor 2 (HER2) antibody, has been shown to be an effective radiosensitizer in preclinical studies. The present Phase II trial evaluated trastuzumab plus radiotherapy in patients with HER2-positive, chemotherapy-refractory, locally advanced or locoregionally recurrent breast cancer. Methods and Materials: Eligible patients had measurable disease, normal cardiac function, and biopsy-confirmed residual HER2-positive disease. Patients received weekly trastuzumab (2 mg/kg intravenously), concurrent with radiotherapy (50 Gy) to the breast and regional lymph nodes for 5 weeks. If feasible, surgery followed radiotherapy. The primary endpoint was safety, and the secondary endpoint was efficacy (pathologic response and interval to symptomatic local progression). Results: Of the 19 patients enrolled, 7 were ineligible and received radiotherapy alone and 12 received therapy per protocol. Of these 12 patients, 11 had a Stage T4 diagnosis. Grade 3 toxicities included skin (n = 2) and lymphopenia (n = 1). One patient experienced delayed wound healing after surgery. No patients developed symptomatic cardiac dysfunction. Of the 7 patients who had undergone mastectomy, 3 (43%) had a substantial pathologic response (complete response or microscopic residual disease), significantly more than a comparison cohort (2 of 38 or 5%, p = .02). The median interval to symptomatic local progression was not reached. The median overall survival was 39 months. Conclusion: This is the first prospective trial providing evidence for a radiosensitizing effect of trastuzumab in breast cancer. The combination of trastuzumab and radiotherapy was well tolerated.

• OSTI ID: 21372152
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 4 Vol. 76; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
ANTIBODIES
BODY
CHEMOTHERAPY
DISEASES
DRUGS
GLANDS
GROWTH FACTORS
LYMPH NODES
LYMPHATIC SYSTEM
MAMMARY GLANDS
MEDICINE
MEMBRANE PROTEINS
MITOGENS
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NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANS
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RADIOSENSITIZERS
RADIOTHERAPY
RECEPTORS
RESPONSE MODIFYING FACTORS
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THERAPY
TOXICITY