BACKGROUND: Cisplatin is a highly effective chemotherapeutic agent against epithelial ovarian cancer but is associated with significant toxicities. SPI-77 is a liposomal pegylated formulation of cisplatin that was developed to reduce systemic toxicity and to better deliver cisplatin to tumors. We assessed the response rates and safety of SPI-77, in patients with recurrent epithelial ovarian cancer. PATIENTS AND METHODS: Patients were selected for having previously achieved a platinum treatment free interval of greater than 6 months (e.g. platinum-sensitive) and high potential of achieving responses when rechallenged with a platinum drug. SPI-77 was administered at a dose of 260 mg/m(2) every 21 days until disease progression. RESULTS: Enrollment was terminated after 5 patients were treated because of concern with the adequacy of the formulation. Four out of the five patients had stable disease as best response. While no serious, unexpected adverse events occurred in spite of large cumulative doses of SPI-77, there were concerns related to the large lipid load and prolonged persistence of residual platinum in body stores. CONCLUSION: The results of this study, although inconclusive regarding its primary endpoints, provide some important lessons for the development of similar liposomal platinum agents.
BACKGROUND:Cisplatin is a highly effective chemotherapeutic agent against epithelial ovarian cancer but is associated with significant toxicities. SPI-77 is a liposomal pegylated formulation of cisplatin that was developed to reduce systemic toxicity and to better deliver cisplatin to tumors. We assessed the response rates and safety of SPI-77, in patients with recurrent epithelial ovarian cancer. PATIENTS AND METHODS: Patients were selected for having previously achieved a platinum treatment free interval of greater than 6 months (e.g. platinum-sensitive) and high potential of achieving responses when rechallenged with a platinum drug. SPI-77 was administered at a dose of 260 mg/m(2) every 21 days until disease progression. RESULTS: Enrollment was terminated after 5 patients were treated because of concern with the adequacy of the formulation. Four out of the five patients had stable disease as best response. While no serious, unexpected adverse events occurred in spite of large cumulative doses of SPI-77, there were concerns related to the large lipid load and prolonged persistence of residual platinum in body stores. CONCLUSION: The results of this study, although inconclusive regarding its primary endpoints, provide some important lessons for the development of similar liposomal platinum agents.
Authors: Thomas J Anchordoquy; Yechezkel Barenholz; Diana Boraschi; Michael Chorny; Paolo Decuzzi; Marina A Dobrovolskaia; Z Shadi Farhangrazi; Dorothy Farrell; Alberto Gabizon; Hamidreza Ghandehari; Biana Godin; Ninh M La-Beck; Julia Ljubimova; S Moein Moghimi; Len Pagliaro; Ji-Ho Park; Dan Peer; Erkki Ruoslahti; Natalie J Serkova; Dmitri Simberg Journal: ACS Nano Date: 2017-01-09 Impact factor: 15.881
Authors: Hardeep S Oberoi; Natalia V Nukolova; Alexander V Kabanov; Tatiana K Bronich Journal: Adv Drug Deliv Rev Date: 2013-10-08 Impact factor: 15.470
Authors: Zahid Hussain; Shahzeb Khan; Muhammad Imran; Muhammad Sohail; Syed Wadood Ali Shah; Marcel de Matas Journal: Drug Deliv Transl Res Date: 2019-06 Impact factor: 4.617
Authors: Amit A Vernekar; Gilles Berger; Anna E Czapar; Frank A Veliz; David I Wang; Nicole F Steinmetz; Stephen J Lippard Journal: J Am Chem Soc Date: 2018-03-19 Impact factor: 15.419