Impact of pegfilgrastim as primary prophylaxis for metastatic castration-resistant prostate cancer patients undergoing cabazitaxel treatment: an open-label study in Japan
Takeo Kosaka, Hiroji Uemura, Makoto Sumitomo, Kenichi Harada, Mikio Sugimoto, Narihiko Hayashi, Kazuhiro Yoshimura, Satoshi Fukasawa, Evelyne Ecstein-Fraisse, Yoshinori Sunaga, Mototsugu Oya, Takeo Kosaka, Hiroji Uemura, Makoto Sumitomo, Kenichi Harada, Mikio Sugimoto, Narihiko Hayashi, Kazuhiro Yoshimura, Satoshi Fukasawa, Evelyne Ecstein-Fraisse, Yoshinori Sunaga, Mototsugu Oya
Abstract
Background: Cabazitaxel is an efficacious treatment for patients with metastatic castration-resistant prostate cancer who have previously progressed on docetaxel, but febrile neutropenia during the first cycle is a frequent complication. Asian patients are at increased risk of febrile neutropenia. Although primary prophylaxis with granulocyte colony-stimulating factor can reduce the incidence, its efficacy has not been prospectively demonstrated in Japanese patients with cabazitaxel treatment.
Methods: PEGAZUS, a prospective, single-arm study conducted at eight clinical sites in Japan, enrolled 21 heavily pretreated patients with metastatic castration-resistant prostate cancer. Patients received cabazitaxel 25 mg/m2 every 3 weeks, up to 10 cycles. Oral prednisolone 10 mg was taken daily. Pegfilgrastim 3.6 mg was administered at least 24 h after the cabazitaxel infusion. The primary endpoint was the incidence of febrile neutropenia in the first cycle.
Results: The median number of treatment cycles was seven. The relative dose intensity of cabazitaxel was 67.4% (range, 53.2-91.3%). Two of 21 patients (9.5%) experienced febrile neutropenia in the first cycle. This rate was lower than the rate (43%) previously observed without prophylactic granulocyte colony-stimulating factor in a similar patient population. Six patients showed a prostate-specific antigen response (28.6%). Three of four patients evaluable for tumor response had stable disease and one had progressive disease. Grade ≥3 diarrhea was not observed. Primary prophylaxis with granulocyte colony-stimulating factor significantly reduced the incidence of febrile neutropenia in this study.
Conclusions: Cabazitaxel plus granulocyte colony-stimulating factor is safe and effective for Japanese patients with metastatic castration-resistant prostate cancer who have previously progressed on docetaxel. Clinical trial registration: ClinicalTrials.gov (NCT02441894).
Keywords: Asian; febrile neutropenia; pegylated granulocyte colony-stimulating factor; prostate-specific antigen; taxane.
© The Author(s) 2019. Published by Oxford University Press.
Figures
References
- Bissery MC, Bouchard H, Riou J, et al. . Preclinical evaluation of TXD258, a new taxoid. Proc Am Assoc Cancer Res 2000;41:1364.
- Aller AW, Kraus LA, Bissery MC. In vitro activity of TXD258 in chemotherapeutic resistant tumor cell lines. Proc Am Assoc Cancer Res 2000;41:303.
- Bissery MC. Preclinical evaluation of new taxoids. Curr Pharm Des 2001;7:1251–7.
- Bouchet BP, Galmarini CM. Cabazitaxel, a new taxane with favorable properties. Drugs Today 2010;46:735–42.
- de Bono JS, Oudard S, Ozguroglu M, et al. . Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010;376:1147–54.
- Japanese Society of Medical Oncology Practical Guideline of Febrile Neutropenia (FN). Tokyo: Nankodo, 2012.
- Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 2006;106:2258–66.
- Talcott JA, Siegel RD, Finberg R, Goldman L. Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule. J Clin Oncol 1992;10:316–22.
- Chrischilles EA, Link BK, Scott SD, Delgado DJ, Fridman M. Factors associated with early termination of CHOP therapy and the impact on survival among patients with chemosensitive intermediate-grade non-Hodgkin’s lymphoma. Cancer Control 2003;10:396–403.
- Chow LWC, Biganzoli L, Leo AD, et al. . Toxicity profile differences of adjuvant docetaxel/cyclophosphamide (TC) between Asian and Caucasian breast cancer patients. Asia Pac J Clin Oncol 2017;13:372–8.
- Nozawa M, Mukai H, Takahashi S, et al. . Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer. Int J Clin Oncol 2015;20:1026–34.
- Roberts AW. G-CSF: A key regulator of neutrophil production, but that’s not all! Growth Factors 2005;23:33–41.
- Siena S, Piccart MJ, Holmes FA, Glaspy J, Hackett J, Renwick JJ. A combined analysis of two pivotal randomized trials of a single dose of pegfilgrastim per chemotherapy cycle and daily Filgrastim in patients with stage II-IV breast cancer. Oncol Rep 2003;10:715–24.
- JEVTANA® (cabazitaxel) injection [Highlights of prescribing information]: Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2018. Accessed 17 July 2018. Available from .
- Japanese Urological Association Clinical Practice Guideline for Prostate Cancer. Osaka: Medical Review, 2016.
- Smith TJ, Bohlke K, Lyman GH, et al. . Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2015;33:3199–212.
- Cooper KL, Madan J, Whyte S, Stevenson MD, Akehurst RL. Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis. BMC Cancer 2011;11:404.
- Yasufuku T, Shigemura K, Tanaka K, Arakawa S, Miyake H, Fujisawa M.. Risk factors for refractory febrile neutropenia in urological chemotherapy. J Infect Chemother 2013;19:211–6.
- Shigeta K, Kosaka T, Yazawa S, et al. . Predictive factors for severe and febrile neutropenia during docetaxel chemotherapy for castration-resistant prostate cancer. Int J Clin Oncol 2015;20:605–12.
- U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. 2009. Available from: .
- Yano R, Konno A, Watanabe K, et al. . Pharmacoethnicity of docetaxel-induced severe neutropenia: integrated analysis of published phase II and III trials. Int J Clin Oncol 2013;18:96–104.
- Chan A, Fu WH, Shih V, Coyuco JC, Tan SH, Ng R. Impact of colony-stimulating factors to reduce febrile neutropenic events in breast cancer patients receiving docetaxel plus cyclophosphamide chemotherapy. Support Care Cancer 2011;19:497–504.
- Eisenberger M, Hardy-Bessard AC, Kim CS, et al. . Phase III study comparing a reduced dose of cabazitaxel (20 mg/m2) and the currently approved dose (25 mg/m2) in postdocetaxel patients with metastatic castration-resistant prostate cancer-PROSELICA. J Clin Oncol 2017;35:3198–206.
Source: PubMed