BACKGROUND: Botanical therapies are often used by breast cancer patients yet few clinical trials have evaluated their safety and efficacy. We studied mechanisms of activity and performed a phase I clinical trial in patients with advanced breast cancer to evaluate BZL101, an aqueous extract from Scutellaria barbata. METHODS: Preclinical studies were conducted in vitro to characterize cell death induced by BZL101. In a phase I trial, eligible patients had histologically confirmed, measurable metastatic breast cancer. Treatment consisted of 350 ml per day of oral BZL101, administered as sole cancer therapy until disease progression, toxicity or personal preference to discontinue. Primary endpoints were safety, toxicity and tumor response. RESULTS: BZL101 extract induced strong growth inhibition and apoptosis of breast cancer cell lines. In the phase I trial, 21 patients received BZL101. Mean age was 54 years (30-77) and mean number of prior treatments for metastatic disease was 3.9 (0-10). There were no grade III or IV adverse events (AEs). The most frequently reported BZL101-related grade I and II AEs included: nausea (38%), diarrhea (24%), headache (19%) flatulence (14%), vomiting (10%), constipation (10%), and fatigue (10%). Sixteen patients were evaluable for response. Four patients had stable disease (SD) for >90 days (25%) and 3/16 had SD for >180 days (19%). Five patients had objective tumor regression, one of which was 1 mm short of a PR based on RECIST criteria. CONCLUSIONS: BZL 101 inhibits breast cancer cell lines by inducing apoptosis. In a phase I clinical trial, BZL101 was safe and had a favorable toxicity profile. BZL101 demonstrated encouraging clinical activity in this heavily pretreated population.
BACKGROUND: Botanical therapies are often used by breast cancerpatients yet few clinical trials have evaluated their safety and efficacy. We studied mechanisms of activity and performed a phase I clinical trial in patients with advanced breast cancer to evaluate BZL101, an aqueous extract from Scutellaria barbata. METHODS: Preclinical studies were conducted in vitro to characterize cell death induced by BZL101. In a phase I trial, eligible patients had histologically confirmed, measurable metastatic breast cancer. Treatment consisted of 350 ml per day of oral BZL101, administered as sole cancer therapy until disease progression, toxicity or personal preference to discontinue. Primary endpoints were safety, toxicity and tumor response. RESULTS: BZL101 extract induced strong growth inhibition and apoptosis of breast cancer cell lines. In the phase I trial, 21 patients received BZL101. Mean age was 54 years (30-77) and mean number of prior treatments for metastatic disease was 3.9 (0-10). There were no grade III or IV adverse events (AEs). The most frequently reported BZL101-related grade I and II AEs included: nausea (38%), diarrhea (24%), headache (19%) flatulence (14%), vomiting (10%), constipation (10%), and fatigue (10%). Sixteen patients were evaluable for response. Four patients had stable disease (SD) for >90 days (25%) and 3/16 had SD for >180 days (19%). Five patients had objective tumor regression, one of which was 1 mm short of a PR based on RECIST criteria. CONCLUSIONS: BZL 101 inhibits breast cancer cell lines by inducing apoptosis. In a phase I clinical trial, BZL101 was safe and had a favorable toxicity profile. BZL101 demonstrated encouraging clinical activity in this heavily pretreated population.
Authors: K H Oh; S W Yang; J M Park; J H Seol; S Iemura; T Natsume; S Murata; K Tanaka; Y J Jeon; C H Chung Journal: Cell Death Differ Date: 2011-02-04 Impact factor: 15.828
Authors: Keith I Block; Charlotte Gyllenhaal; Leroy Lowe; Amedeo Amedei; A R M Ruhul Amin; Amr Amin; Katia Aquilano; Jack Arbiser; Alexandra Arreola; Alla Arzumanyan; S Salman Ashraf; Asfar S Azmi; Fabian Benencia; Dipita Bhakta; Alan Bilsland; Anupam Bishayee; Stacy W Blain; Penny B Block; Chandra S Boosani; Thomas E Carey; Amancio Carnero; Marianeve Carotenuto; Stephanie C Casey; Mrinmay Chakrabarti; Rupesh Chaturvedi; Georgia Zhuo Chen; Helen Chen; Sophie Chen; Yi Charlie Chen; Beom K Choi; Maria Rosa Ciriolo; Helen M Coley; Andrew R Collins; Marisa Connell; Sarah Crawford; Colleen S Curran; Charlotta Dabrosin; Giovanna Damia; Santanu Dasgupta; Ralph J DeBerardinis; William K Decker; Punita Dhawan; Anna Mae E Diehl; Jin-Tang Dong; Q Ping Dou; Janice E Drew; Eyad Elkord; Bassel El-Rayes; Mark A Feitelson; Dean W Felsher; Lynnette R Ferguson; Carmela Fimognari; Gary L Firestone; Christian Frezza; Hiromasa Fujii; Mark M Fuster; Daniele Generali; Alexandros G Georgakilas; Frank Gieseler; Michael Gilbertson; Michelle F Green; Brendan Grue; Gunjan Guha; Dorota Halicka; William G Helferich; Petr Heneberg; Patricia Hentosh; Matthew D Hirschey; Lorne J Hofseth; Randall F Holcombe; Kanya Honoki; Hsue-Yin Hsu; Gloria S Huang; Lasse D Jensen; Wen G Jiang; Lee W Jones; Phillip A Karpowicz; W Nicol Keith; Sid P Kerkar; Gazala N Khan; Mahin Khatami; Young H Ko; Omer Kucuk; Rob J Kulathinal; Nagi B Kumar; Byoung S Kwon; Anne Le; Michael A Lea; Ho-Young Lee; Terry Lichtor; Liang-Tzung Lin; Jason W Locasale; Bal L Lokeshwar; Valter D Longo; Costas A Lyssiotis; Karen L MacKenzie; Meenakshi Malhotra; Maria Marino; Maria L Martinez-Chantar; Ander Matheu; Christopher Maxwell; Eoin McDonnell; Alan K Meeker; Mahya Mehrmohamadi; Kapil Mehta; Gregory A Michelotti; Ramzi M Mohammad; Sulma I Mohammed; D James Morre; Vinayak Muralidhar; Irfana Muqbil; Michael P Murphy; Ganji Purnachandra Nagaraju; Rita Nahta; Elena Niccolai; Somaira Nowsheen; Carolina Panis; Francesco Pantano; Virginia R Parslow; Graham Pawelec; Peter L Pedersen; Brad Poore; Deepak Poudyal; Satya Prakash; Mark Prince; Lizzia Raffaghello; Jeffrey C Rathmell; W Kimryn Rathmell; Swapan K Ray; Jörg Reichrath; Sarallah Rezazadeh; Domenico Ribatti; Luigi Ricciardiello; R Brooks Robey; Francis Rodier; H P Vasantha Rupasinghe; Gian Luigi Russo; Elizabeth P Ryan; Abbas K Samadi; Isidro Sanchez-Garcia; Andrew J Sanders; Daniele Santini; Malancha Sarkar; Tetsuro Sasada; Neeraj K Saxena; Rodney E Shackelford; H M C Shantha Kumara; Dipali Sharma; Dong M Shin; David Sidransky; Markus David Siegelin; Emanuela Signori; Neetu Singh; Sharanya Sivanand; Daniel Sliva; Carl Smythe; Carmela Spagnuolo; Diana M Stafforini; John Stagg; Pochi R Subbarayan; Tabetha Sundin; Wamidh H Talib; Sarah K Thompson; Phuoc T Tran; Hendrik Ungefroren; Matthew G Vander Heiden; Vasundara Venkateswaran; Dass S Vinay; Panagiotis J Vlachostergios; Zongwei Wang; Kathryn E Wellen; Richard L Whelan; Eddy S Yang; Huanjie Yang; Xujuan Yang; Paul Yaswen; Clement Yedjou; Xin Yin; Jiyue Zhu; Massimo Zollo Journal: Semin Cancer Biol Date: 2015-12 Impact factor: 15.707