1. A Phase 1 Dose-Escalation Trial of Radiation Therapy and Concurrent Cisplatin for Stage II and III Triple-Negative Breast Cancer.
- Author
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Bellon, Jennifer R., Chen, Yu-Hui, Rees, Rebecca, Taghian, Alphonse G., Wong, Julia S., Punglia, Rinaa S., Shiloh, Ron Y., Warren, Laura E.G., Krishnan, Monica S., Phillips, John, Pretz, Jennifer, Jimenez, Rachel, Macausland, Stephanie, Pashtan, Itai, Andrews, Chelsea, Isakoff, Steven J., Winer, Eric P., and Tolaney, Sara M.
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TRIPLE-negative breast cancer , *CISPLATIN , *RADIOTHERAPY , *MASTECTOMY , *PROGRESSION-free survival , *BREAST tumor treatment , *RESEARCH , *DRUG dosage , *RESEARCH methodology , *MEDICAL cooperation , *EVALUATION research , *TUMOR classification , *COMPARATIVE studies , *COMBINED modality therapy , *LUMPECTOMY , *BREAST tumors , *DRUG toxicity , *LONGITUDINAL method - Abstract
Purpose: Patients with triple-negative breast cancer (TNBC) experience higher local-regional recurrence rates than those with luminal or HER2-positive tumors. This prospective, phase 1B trial was designed to assess the safety and to establish the maximum tolerated dose (MTD) of cisplatin with radiation therapy for women with early-stage TNBC.Methods and Materials: Eligible patients had stage II or III TNBC. Cisplatin was initiated at 10 mg/m2 intravenously once weekly during radiation and then escalated in a 3 + 3 design by 10 mg/m2 at each dose level until 40 mg/m2, or the MTD, was reached. Patients undergoing breast-conserving therapy (BCT) or mastectomy were accrued in separate parallel cohorts during dose escalation, followed by a 10-patient expansion at the MTD.Results: During 2013 to 2018, 55 patients were accrued. Four patients developed dose-limiting toxicity. In the BCT cohort, 1 patient receiving 40 mg/m2 developed tinnitus resulting in a cisplatin delay; therefore, this was the BCT cohort MTD. In the mastectomy cohort, 1 patient receiving 20 mg/m2 developed a grade 3 urinary infection, and 2 additional patients had dose-limiting toxicities at 40 mg/m2 (grade 3 neutropenia and grade 2 tinnitus), both resulting in cisplatin delay. Thus, 30 mg/m2 was the mastectomy cohort MTD. Median follow-up was 48.5 months. Three-year disease-free survival was 74.7% for the BCT cohort and 64.4% for the mastectomy cohort.Conclusions: Adjuvant radiation therapy with concurrent cisplatin is feasible with a recommended phase 2 dose of 30 mg/m2 and 40 mg/m2 intravenously weekly in mastectomy and BCT cohorts, respectively. [ABSTRACT FROM AUTHOR]- Published
- 2021
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