Efficacy of Oral Etoposide in Pretreated Metastatic Breast Cancer

No standard chemotherapy has been defined for metastatic breast cancer (MBC) patients pretreated with anthracyclines and taxanes. A multicenter phase 2 study was conducted to evaluate the safety and efficacy of oral etoposide in patients with MBC. Eligible patients were treated with repeated cycles of oral etoposide (60 mg/m/d on days 1–10, followed by 11 days of rest). The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate, clinical benefit rate (CBR), and toxicity profiles. Seventy-five women with MBC were enrolled at 10 centers in China. Seven (9.3%) patients achieved partial response (PR) and 29 (38.7%) had stable disease (SD). Nine patients (12%) had SD for >24 weeks and the CBR was 21.3% (16/75). The median PFS was 4.5 (range, 1.3–7.7) months. Of the 38 patients who received 3 regimens prior to this study, 2 (5.3%) had PR and 3 (7.9%) had SD for >24 weeks, with a CBR of 13.2%. The reported grade 3/4 adverse events included leukopenia (13.3%, n1⁄4 10), neutropenia (17.9%, n1⁄4 14), anemia (2.7%, n1⁄4 2), vomiting (2.6%, n1⁄4 2), and alopecia (1.3%, n1⁄4 1). Oral etoposide was effective and well tolerated in Chinese women with pretreated MBC. (Medicine 94(17):e774) Abbreviations: BC = breast cancer, CBR = clinical benefit rate, CR = complete response, CT = computed tomography, ITT = intention to treat, MBC = metastatic breast cancer, PD = ai, MD, Hong Da MD, d Binghe Xu, MD INTRODUCTION S ignificant and worldwide progress in the early detection and comprehensive treatment of breast cancer (BC) has been made in recent years. However, it has been estimated that 30% of the patients initially diagnosed with early-stage BC will eventually develop metastatic breast cancer (MBC). In most cases, MBC remains an incurable disease. Therefore, the systemic treatment of MBC prolongs survival and enhances quality of life, but is not curative. Anthracyclines and taxanes are the preferred cytotoxic drugs for the treatment of MBC. Other agents, including capecitabine, gemcitabine, vinorelbine, and others, are also available as treatment options and can be used in cases that were pretreated with at least an anthracycline and a taxane. For patients who have failed 3 chemotherapy regimens, there are no standard therapeutic schedules. Most guidelines suggest best supportive therapy or participation in clinical trials. Etoposide is a semisynthetic derivative of podophyllotoxin that can induce cell cycle arrest at the late S phase and early G2 phase. Although it has been administered intravenously to MBC patients with disappointing results, a number of preclinical and clinical studies have demonstrated the schedule dependency of etoposide efficacy. In a phase 1 clinical trial, a variety of solid tumors showed responses to prolonged etoposide exposure. Hainsworth et al proposed a schedule of chronic oral etoposide of 50 mg/m/d for 21 consecutive days every 4 weeks. Additionally, sensitivity to oral etoposide has been demonstrated in small cell lung cancer, nonsmall-cell lung cancer, non-Hodgkin lymphoma, germ cell tumors, and BC. Furthermore, the prolonged schedule of administration of single-agent oral etoposide has been tested in recurrent or MBC in five phase 2 clinical trials. The numbers of patients enrolled and the response rates in these studies are listed in Table 1. It is important to note that all of these studies included small sample sizes and were conducted before granulocyte colony-stimulating factor was used in clinical practice. Additionally, there is a lack of data pertaining to the efficacy and safety of oral etoposide in Chinese patients with MBC. In 2012, we reported our single-center study of oral etoposide in a group of Chinese patients with heavily treated MBC, the results of which suggested that oral etoposide could be an option for this patient population. To further elucidate the efficacy of oral etoposide, we conducted a multicenter phase 2 study in Chinese patients with MBC who were pretreated with anthracyclines and taxanes.