Phase I study of nanoparticle albumin-bound paclitaxel, carboplatin and trastuzumab in women with human epidermal growth factor receptor 2-overexpressing breast cancer

Tezuka,Kenji; Takashima,Tsutomu; Kashiwagi,Shinichiro; Kawajiri,Hidemi; Tokunaga,Shinya; Tei,Seika; Nishimura,Shigehiko; Yamagata,Shigehito; Noda,Satoru; Nishimori,Takeo; Mizuyama,Yoko; Sunami,Takeshi; Ikeda,Katsumi; Ogawa,Yoshinari; Onoda,Naoyoshi; Ishikawa,Tetsuro; Kudoh,Shinzoh; Takada,Minoru; Hirakawa,Kosei

doi:10.3892/mco.2017.1176

April-2017 Volume 6 Issue 4

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April-2017 Volume 6 Issue 4

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Article

Phase I study of nanoparticle albumin-bound paclitaxel, carboplatin and trastuzumab in women with human epidermal growth factor receptor 2-overexpressing breast cancer

Authors:
- Kenji Tezuka
- Tsutomu Takashima
- Shinichiro Kashiwagi
- Hidemi Kawajiri
- Shinya Tokunaga
- Seika Tei
- Shigehiko Nishimura
- Shigehito Yamagata
- Satoru Noda
- Takeo Nishimori
- Yoko Mizuyama
- Takeshi Sunami
- Katsumi Ikeda
- Yoshinari Ogawa
- Naoyoshi Onoda
- Tetsuro Ishikawa
- Shinzoh Kudoh
- Minoru Takada
- Kosei Hirakawa
View Affiliations / Copyright

Affiliations: Department of Breast Surgery, National Hospital Organization Kinki‑Chuo Chest Medical Center, Sakai, Osaka 591‑8555, Japan, Department of Surgical Oncology, Osaka University Graduate School of Medicine, Osaka 545‑8585, Japan, Department of Head, Neck and Breast Surgery, Ishikiriseiki Hospital, Higashiosaka, Osaka 579‑8026, Japan, Department of Clinical Oncology, Osaka General Hospital, Osaka 534‑0021, Japan, Department of Surgery, Seichokai Fuchu Hospital, Izumi, Osaka 594‑0076, Japan, Department of Surgery, Sumitomo Hospital, Osaka 530‑0005, Japan, Department of Surgery, Ikuwakai Memorial Hospital, Osaka 544‑0004, Japan, Department of Surgery, Ohno Memorial Hospital, Osaka, Osaka 550‑0015, Japan, Department of Surgery, Izumi Municipal Hospital, Izumi, Osaka 594‑0071, Japan, Department of Breast Surgery, Osaka General Hospital, Osaka 534‑0021, Japan, Department of Surgery, Kashiwara Municipal Hospital, Kashiwara, Osaka 582‑0005, Japan, Department of Internal Medicine, Osaka Socio‑Medical Center Hospital, Osaka 557‑0004, Japan, Hanwa Daini Senboku Hospital, Sakai, Osaka 599‑8271, Japan
Pages: 534-538
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Published online on: February 24, 2017

https://doi.org/10.3892/mco.2017.1176
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Abstract

Although the concurrent use of anthracycline-containing chemotherapy and taxane with trastuzumab are considered the treatment of choice for the primary systemic therapy of human epidermal growth factor receptor 2 (HER2)-overexpressing early breast cancer, non‑anthracycline regimens, such as concurrent administration of docetaxel and carboplatin with trastuzumab, exhibited similar efficacies in a previous study. In addition, tri‑weekly treatment with nanoparticle albumin‑bound paclitaxel (nab‑paclitaxel) resulted in significantly higher response rates and a favorable safety profile compared with standard paclitaxel for metastatic breast cancer patients in another phase III study. Based on these results, a phase I study of combination therapy with nab-paclitaxel, carboplatin and trastuzumab was planned, in order to estimate its efficacy and safety for HER2-overexpressing locally advanced breast cancer. The present study was designed to determine the dose‑limiting toxicity (DLT), maximum tolerated dose and recommended dose of this combination treatment in women with HER2‑overexpressing locally advanced breast cancer. The starting dose of nab‑paclitaxel was 220 mg/m2 (level 1), and the dose was escalated to 260 mg/m2 (level 2). Nab‑paclitaxel was administered with carboplatin (area under the curve, 6 mg/ml/min) and trastuzumab tri‑weekly. A total of 6 patients were enrolled. Although no DLT was observed during the first cycle, 4 patients developed grade 4 thrombocytopenia, 2 had grade 4 neutropenia and 3 exhibited a grade 4 decrease in hemoglobin levels. In the present phase I study, although no patients experienced DLTs, this regimen was associated with severe hematological toxicities and it was not well tolerated. However, considering the high efficacy and lower risk of cardiotoxicity and secondary carcinogenesis with taxane, platinum and trastuzumab combination therapy, further evaluation of another regimen including weekly administration or a more accurate dose setting should be conducted.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Phase I study of nanoparticle albumin-bound paclitaxel, carboplatin and trastuzumab in women with human epidermal growth factor receptor 2-overexpressing breast cancer

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