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Phase II clinical trial of metronomic chemotherapy with combined irinotecan and tegafur–gimeracil–oteracil potassium in metastatic and recurrent breast cancer

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Abstract

Background

We investigated the efficacy and safety of metronomic chemotherapy with combined irinotecan and tegafur–gimeracil–oteracil potassium (TS-1) in patients with metastatic and recurrent breast cancer (MRBC), and the association between irinotecan metabolizing enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) gene polymorphisms and adverse events.

Methods

The study group comprised 40 patients aged 35–79 years. Irinotecan (60 mg/m2 in 5 % dextrose) was administered by 120-min infusion on days 1, 8, and 15 every 4 weeks. TS-1 (prescribed in a standard quantity) was administered at 80 mg/m2/day orally on days 3–7, 10–14, and 17–21 every 4 weeks.

Results

Tumor response data were available for 34 patients. Median follow-up was 12 months (range 1–45 months). Response rate was 47 % (one complete and 15 partial responses). Stable disease was observed in 17 patients (50 %). One patient had disease progression (3 %). Median progression-free survival was 14 months [95 % confidence interval (CI), 10–26]. Median overall survival was 26 months (95 % CI not calculable owing to sample size), and 79.3 % of patients survived for 1 year. The most common grade 3 or 4 adverse events were neutropenia (15 %), leukopenia (12.5 %), diarrhea (7.5 %), and anemia (2.5 %). All other adverse events were grade 1 or 2. Treatment-related toxicity was generally modest and manageable. No significant correlation was observed between UGT1A1 polymorphisms and hematological or non-hematological toxicities.

Conclusions

Metronomic chemotherapy with combined irinotecan and TS-1 was effective in MRBC patients. Adverse effects were mild and the regimen was safely administered without identifying UGT1A1 polymorphisms.

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Acknowledgments

We thank all patients who participated in this study and all the investigators (Dr. Toshihiro Koga: Hirose Hospital, Dr. Hiroshi Yanaga: Yanaga Kyouritsu Hospital, Dr. Kosuke Tayama: Tayama Medical Clinic and Dr. Hiroya Tanaka : Tanaka Clinic).

Conflict of interest

The authors confirm that there are no actual or potential conflicts of interest relating to this article.

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Authors and Affiliations

  1. Department of Surgery, Kurume University, 67 Asahi-machi, Kurume, 830-0011, Japan

    Hiroko Otsuka, Uhi Toh, Nobutaka Iwakuma, Ryuji Takahashi, Mai Mishima, Miki Takenaka & Kazuo Shirouzu

  2. Multidisciplinary Cancer Treatment Center, Kurume University, Kurume, 67 Asahi-machi, Kurume, 830-0011, Japan

    Teruhiko Fujii

  3. Biostatistics Center, Kurume University, Kurume, 67 Asahi-machi, Kurume, 830-0011, Japan

    Tatsuyuki Kakuma

  4. Social Insurance Kurume Daiichi Hospital, 21 Kushihara-Machi, Kurume, 830-0013, Japan

    Maki Tanaka

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  1. Hiroko Otsuka
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Correspondence to Teruhiko Fujii.

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Otsuka, H., Fujii, T., Toh, U. et al. Phase II clinical trial of metronomic chemotherapy with combined irinotecan and tegafur–gimeracil–oteracil potassium in metastatic and recurrent breast cancer. Breast Cancer 22, 335–342 (2015). https://doi.org/10.1007/s12282-013-0483-1

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