A Phase II Study to Evaluate the Safety and Efficacy of Pegteograstim in Korean Breast Cancer Patients Receiving Dose-Dense Doxorubicin/Cyclophosphamide
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Purpose Dose-dense chemotherapy (DD-CT) is a preferred (neo)adjuvant regimen in early breast cancer (BC). Although the results of reported randomized trials are conflicting, a recent metaanalysis showed improved overall and disease-free survival with DD-CT compared to conventional schedules. However, no DD-CT safety data for Korean BC patients are available. This phase II study was conducted to evaluate the safety and efficacy of pegteograstim in Korean BC patients receiving DD-CT. Materials and Methods Patients with operable (stage I-III), histologically confirmed BC received four cycles of intravenous doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 every 2 weeks as neoadjuvant or adjuvant therapy. Pegteograstim (6.0 mg) was administered subcutaneously on day 2 of each cycle. The primary endpoint was the incidence of febrile neutropenia (FN). The secondary endpoints were safety and tolerability. Results Of 63 patients, one (1.6%) developed FN during all cycles of DD-CT. Dose delay was observed in four patients (6.3%) and dose reduction in two (3.2%) during DD-CT. Frequent adverse events (AEs) were nausea, alopecia, generalized muscle weakness, myalgia, mucositis, anorexia, dyspepsia, and diarrhea; most AEs were related to chemotherapy. Grade 3-4 AEs were reported in five of 63 patients (7.9%), and all grade 3 and 4 AEs were related to chemotherapy. Adverse drug reactions possibly linked to pegteograstim were abdominal pain, bone pain, myalgia, generalized muscle weakness, and headache in five of 63 patients (7.9%). Conclusion Dose-dense AC (doxorubicin/cyclophosphamide) chemotherapy with pegteograstim support is a tolerable and safe regimen in Korean early BC patients.
Abstract
Purpose Dose-dense chemotherapy (DD-CT) is a preferred (neo)adjuvant regimen in early breast cancer (BC). Although the results of reported randomized trials are conflicting, a recent metaanalysis showed improved overall and disease-free survival with DD-CT compared to conventional schedules. However, no DD-CT safety data for Korean BC patients are available. This phase II study was conducted to evaluate the safety and efficacy of pegteograstim in Korean BC patients receiving DD-CT. Materials and Methods Patients with operable (stage I-III), histologically confirmed BC received four cycles of intravenous doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 every 2 weeks as neoadjuvant or adjuvant therapy. Pegteograstim (6.0 mg) was administered subcutaneously on day 2 of each cycle. The primary endpoint was the incidence of febrile neutropenia (FN). The secondary endpoints were safety and tolerability. Results Of 63 patients, one (1.6%) developed FN during all cycles of DD-CT. Dose delay was observed in four patients (6.3%) and dose reduction in two (3.2%) during DD-CT. Frequent adverse events (AEs) were nausea, alopecia, generalized muscle weakness, myalgia, mucositis, anorexia, dyspepsia, and diarrhea; most AEs were related to chemotherapy. Grade 3-4 AEs were reported in five of 63 patients (7.9%), and all grade 3 and 4 AEs were related to chemotherapy. Adverse drug reactions possibly linked to pegteograstim were abdominal pain, bone pain, myalgia, generalized muscle weakness, and headache in five of 63 patients (7.9%). Conclusion Dose-dense AC (doxorubicin/cyclophosphamide) chemotherapy with pegteograstim support is a tolerable and safe regimen in Korean early BC patients.
참고문헌 (19)
- Early Breast Cancer Trialists' Collaborative Group, "Comparisons between different polychemotherapy regimens for early breast cancer : meta-analyses of long-term outcome among 100, 000women in 123 randomised trials", Lancet, 379, pp.432~444 (2012)
- Del Mastro L, "Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer : an open-label, 2 x 2 factorial, randomised phase 3 trial", Lancet, 385, pp.1863~1872 (2015)
- Citron ML, "Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741", Cancer and Leukemia Group B Trial 9741, 2003, pp.21, 1431~1439
- National Comprehensive Cancer Network, "NCCN clinical practice guidelines in oncology: breast cancer", National Comprehensive Cancer Network, ~ (2018)
- Gray R, "Increasing the dose density of adjuvant chemotherapy by shortening intervals between courses or by sequential drug administration significantly reduces both disease recurrence and breast cancer mortality: an EBCTCG meta-analysis of 21,000 women in 16 randomised trials", San Antonio Breast Cancer Symposium (2018), American Association for Cancer Research
- Venturini M, "Dose-dense adjuvant chemotherapy in early breast cancer patients : results from a randomized trial", J Natl Cancer Inst, 97, pp.1724~1733 (2005)
- Foukakis T, "Effect of tailored dose-dense chemotherapy vs standard 3-weekly adjuvant chemotherapy on recurrence-free survival among women with high-risk early breast cancer : a randomized clinical trial", JAMA, 316, pp.1888~1896 (2016)
- Cameron D, "Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial(CRUK", 05, Lancet Oncol, pp.2017, 18[DOI]
- Mobus V, "Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: final results of AGO phase III iddEPC trial", Ann Oncol, 29, pp.178~185 (2018)
- Waks AG, "Pneumocystis jiroveci pneumonia(PCP)in patients receiving neoadjuvant and adjuvant anthracycline-based chemotherapy for breast cancer : incidence and risk factors", Breast Cancer Res Treat, 154, pp.359~367 (2015)
- Gandara DR, "Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer : a model for assessing population-related pharmacogenomics", J Clin Oncol, 27, pp.3540~3546 (2009)
- Hasegawa Y, "Ethnic difference in hematological toxicity in patients with non-small cell lung cancer treated with chemotherapy : a pooled analysis on Asian versus non-Asian in phase II and III clinical trials", J Thorac Oncol, 6, pp.1881~1888 (2011)
- Wang Y, "Anti-VEGF therapy in mRCC : differences between Asian and non-Asian patients", Br J Cancer, 110, pp.1433~1437 (2014)
- Huang RS, "Effect of population and gender on chemotherapeutic agentinduced cytotoxicity", Mol Cancer Ther, 6, pp.31~36 (2007)
- Chang-gon Kim, "Incidence of Febrile Neutropenia in Korean Female Breast Cancer Patients Receiving Preoperative or Postoperative Doxorubicin", Cyclophosphamide Followed by Docetaxel Chemotherapy, 2016, pp.19(1), 76~82[DOI]
- Hong J, "Characterisation of the site-specific monoPEGylated rhG-CSF analogue pegteograstim", Biologicals, 51, pp.54~61 (2018)
- Shin KH, "An assessment of the pharmacokinetics, pharmacodynamics, and tolerability of GCPGC, a novel pegylated granulocyte colony-stimulating factor(G-CSF), in healthy subjects", Invest New Drugs, 32, pp.636~643 (2014)
- Lee KH, "A randomized, multicenter, phase II", III study to determine the optimal dose and to evaluate the efficacy and safety of pegteograstim(GCPGC)on chemotherapy-induced neutropenia compared to pegfilgrastim in breast cancer patients : KCSG PC10-09, 2016, pp.24, 1709~1717
- Petrelli F, "Adjuvant dose-dense chemotherapy in breast cancer : a systematic review and meta-analysis of randomized trials", Breast Cancer Res Treat, 151, pp.251~259 (2015)