title: Paclitaxel injection concentrate for nanodispersion versus nab-paclitaxel in women with metastatic breast cancer: a multicenter, randomized, comparative phase II/III study.
abstract: Paclitaxel is widely used in the treatment of patients with metastatic breast cancer (MBC). Formulations of paclitaxel contain surfactants and solvents or albumin derived from human blood. The use of co-solvents such as polyoxyethylated castor oil is thought to contribute to toxicity profile and hypersensitivity reactions as well as leaching of plasticizers from polyvinyl chloride bags and infusion sets. Currently, nab-paclitaxel, an albumin-bound paclitaxel in nanometer range continues to be the preferred taxane formulation used in clinic. This study (CTRI/2010/091/001116) investigated the efficacy and tolerability of a polyoxyethylated castor oil- and albumin-free formulation of paclitaxel [paclitaxel injection concentrate for nanodispersion (PICN)] compared with nab-paclitaxel in women with refractory MBC. The current study was a multicenter, open-label, parallel-group, randomized, comparative phase II/III trial evaluating the efficacy and safety of PICN (260 mg/m(2) [n = 64] and 295 mg/m(2) [n = 58] every 3 weeks) compared with nab-paclitaxel (260 mg/m(2) every 3 weeks [n = 58]) in women 18 and 70 years old with confirmed MBC. Overall response rate (ORR) was assessed with imaging every 2 cycles. An independent analysis of radiologic data was performed for evaluable patients. Progression-free survival (PFS) was a secondary efficacy measure. Independent radiologist-assessed ORRs in the evaluable population of women aged ≥70 years were 35, 49, and 43 % in the PICN 260 mg/m(2), PICN 295 mg/m(2), and nab-paclitaxel 260 mg/m(2) arms, respectively. Median PFS in the evaluable population was 23, 35, and 34 weeks in the PICN 260 mg/m(2), PICN 295 mg/m(2), and nab-paclitaxel 260 mg/m(2) arms, respectively. Adverse events occurred in similar proportions of patients across treatment arms. Hypersensitivity reactions were not frequently observed with the clinical use of PICN across the treatment cohorts. In women with metastatic breast cancer, PICN at 260 and 295 mg/m(2) every 3 weeks was effective and well tolerated and showed similar tolerability compared with nab-paclitaxel 260 mg/m(2) every 3 weeks. Statistically, significant differences were not observed in the PICN and nab-paclitaxel treatment arms for radiologist-assessed ORR or median PFS. The novel paclitaxel formulation, PICN, offers apart from efficacy, potential safety advantage of decreased use of corticosteroid pretreatment and the absence of the risk of transmission of blood product-borne disease.
authors.affiliation: KEM Hospital and Research Center, Pune, India.
authors.forename: Minish M
authors.initials: MM
authors.lastname: Jain
authors.affiliation: Cancer Clinic, Nagpur, India.
authors.forename: Smita U
authors.initials: SU
authors.lastname: Gupte
authors.affiliation: HCG Bangalore Institute of Oncology, Bengaluru, India.
authors.forename: Shekhar G
authors.initials: SG
authors.lastname: Patil
authors.affiliation: Cancer Care Clinic, Nagpur, India.
authors.forename: Anand B
authors.initials: AB
authors.lastname: Pathak
authors.affiliation: Deenanath Mangeshkar Hospital and Research Centre, Pune, India.
authors.forename: Chetan D
authors.initials: CD
authors.lastname: Deshmukh
authors.affiliation: Kailash Cancer Hospital and Research Centre, Goraj, India.
authors.forename: Niraj
authors.initials: N
authors.lastname: Bhatt
authors.affiliation: MS Patel Cancer Center, Karamsad, India.
authors.forename: Chiramana
authors.initials: C
authors.lastname: Haritha
authors.affiliation: Kidwai Memorial Institute of Oncology, Bengaluru, India.
authors.forename: K
authors.initials: K
authors.lastname: Govind Babu
authors.affiliation: Shatabdi Super Specialty Hospital, Nashik, India.
authors.forename: Shailesh A
authors.initials: SA
authors.lastname: Bondarde
authors.affiliation: Nizam's Institute of Medical Sciences, Hyderabad, India.
authors.forename: Raghunadharao
authors.initials: R
authors.lastname: Digumarti
authors.affiliation: Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Bajpai
authors.affiliation: Global Hospital, Hyderabad, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Kaushalya Medical Foundation, Thane, India.
authors.forename: Ashish V
authors.initials: AV
authors.lastname: Bakshi
authors.affiliation: Orchid Nursing Home, Kolkata, India.
authors.forename: Gouri Sankar
authors.initials: GS
authors.lastname: Bhattacharya
authors.affiliation: Specialty Cancer Care Department, Manipal Hospital, Bengaluru, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Patil
authors.affiliation: VS Hospital, Chennai, India.
authors.forename: Sundaram
authors.initials: S
authors.lastname: Subramanian
authors.affiliation: Medanta Medicity Hospital, New Delhi, India.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Vaid
authors.affiliation: Hemato-Oncology Clinic, Vedanta Institute of Medical Sciences, Ahmedabad, India.
authors.forename: Chirag J
authors.initials: CJ
authors.lastname: Desai
authors.affiliation: Sun Pharma Advanced Research Co. Ltd., 17/B Mahal Industrial Estate, Mahakali Caves Road, Andheri (E), Mumbai, 400093, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Khopade
authors.affiliation: Sun Pharma Advanced Research Co. Ltd., 17/B Mahal Industrial Estate, Mahakali Caves Road, Andheri (E), Mumbai, 400093, India.
authors.forename: Geetanjali
authors.initials: G
authors.lastname: Chimote
authors.affiliation: Sun Pharma Advanced Research Co. Ltd., 17/B Mahal Industrial Estate, Mahakali Caves Road, Andheri (E), Mumbai, 400093, India.
authors.forename: Poonamalle P
authors.initials: PP
authors.lastname: Bapsy
authors.affiliation: Sun Pharma Advanced Research Co. Ltd., 17/B Mahal Industrial Estate, Mahakali Caves Road, Andheri (E), Mumbai, 400093, India. shravanti.bhowmik@sparcmail.com.
authors.forename: Shravanti
authors.initials: S
authors.lastname: Bhowmik
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007267:Injections; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D000970:Antineoplastic Agents; D017239:Paclitaxel
keywords: Breast neoplasms; Chemistry; Disease-free survival; Paclitaxel; Pharmaceutical