K Oechsle1, F Honecker1, T Cheng2, F Mayer3, P Czaykowski4, E Winquist5, L Wood6, M Fenner7, S Glaesener1, J T Hartmann3, K Chi8, C Bokemeyer1, C Kollmannsberger9. 1. Division of Oncology, Hematology, Bone Marrow Transplantation and Section Pneumology, University Medical Centre Eppendorf, Hamburg University, Hamburg, Germany. 2. Department of Oncology, Tom Baker Cancer Centre, Calgary, Canada. 3. Department of Medical Oncology, Hematology, Rheumatology, Immunology and Pulmonology, University of Tuebingen, Tuebingen, Germany. 4. Department Medical Oncology/Haematology, CancerCare Manitoba, University of Manitoba, Winnipeg. 5. Division of Medical Oncology, London Health Science Centre, London. 6. Division of Medical Oncology, Queen Elizabeth II Health Sciences Centre, Halifax, Canada. 7. Department of Hematology/Hemostaseology/Oncology/Stem Cell Transplantation, Hannover Medical School, Hannover, Germany. 8. Division of Medical Oncology, British Columbia Cancer Agency, University of British Columbia-Vancouver Cancer Centre, Vancouver, Canada. 9. Division of Medical Oncology, British Columbia Cancer Agency, University of British Columbia-Vancouver Cancer Centre, Vancouver, Canada. Electronic address: ckollmannsberger@bccancer.bc.ca.
Abstract
BACKGROUND: The objective of the study was to investigate the activity of sunitinib in a cell line model and subsequently in patients with cisplatin-refractory or multiply relapsed germ cell tumors (GCT). METHODS: The effect of sunitinib on cell proliferation in cisplatin-sensitive and cisplatin-refractory GCT cell lines was evaluated after 48-h sunitinib exposure by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, and IC(50) (concentration that causes 50% inhibition of growth) doses were determined. Sunitinib was subsequently administered at a dose of 50 mg/day for 4 weeks followed by a 2-week break to 33 patients using a Simon two-stage design. RESULTS: Sunitinib demonstrated comparable dose-dependent growth inhibition in cisplatin-sensitive and cisplatin-resistant cell lines, with IC(50) between 3.0 and 3.8 μM. Patient characteristics were as follows: median of 2 (1-6) cisplatin-containing regimens; high-dose chemotherapy 67%; late relapse 33%; and cisplatin refractory or absolute cisplatin refractory 54%. Toxic effects included fatigue (39%), anorexia (21%), diarrhea (27%), mucositis (45%), nausea (33%), hand-foot syndrome (12%), dyspepsia (27%), and skin rash (18%). No unexpected side-effects were observed. Thirty -two of 33 patients were assessable for response. Three confirmed partial responses (PRs) and one unconfirmed PR were seen for a total response rate of 13%. Median progression-free survival (PFS) was 2 months, with a 6-month PFS rate of 11%. CONCLUSIONS: Sunitinib shows in vitro activity in cisplatin-resistant GCT cell lines. Modest clinical activity in heavily pretreated GCT patients was observed.
BACKGROUND: The objective of the study was to investigate the activity of sunitinib in a cell line model and subsequently in patients with cisplatin-refractory or multiply relapsed germ cell tumors (GCT). METHODS: The effect of sunitinib on cell proliferation in cisplatin-sensitive and cisplatin-refractory GCT cell lines was evaluated after 48-h sunitinib exposure by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, and IC(50) (concentration that causes 50% inhibition of growth) doses were determined. Sunitinib was subsequently administered at a dose of 50 mg/day for 4 weeks followed by a 2-week break to 33 patients using a Simon two-stage design. RESULTS:Sunitinib demonstrated comparable dose-dependent growth inhibition in cisplatin-sensitive and cisplatin-resistant cell lines, with IC(50) between 3.0 and 3.8 μM. Patient characteristics were as follows: median of 2 (1-6) cisplatin-containing regimens; high-dose chemotherapy 67%; late relapse 33%; and cisplatin refractory or absolute cisplatin refractory 54%. Toxic effects included fatigue (39%), anorexia (21%), diarrhea (27%), mucositis (45%), nausea (33%), hand-foot syndrome (12%), dyspepsia (27%), and skin rash (18%). No unexpected side-effects were observed. Thirty -two of 33 patients were assessable for response. Three confirmed partial responses (PRs) and one unconfirmed PR were seen for a total response rate of 13%. Median progression-free survival (PFS) was 2 months, with a 6-month PFS rate of 11%. CONCLUSIONS:Sunitinib shows in vitro activity in cisplatin-resistant GCT cell lines. Modest clinical activity in heavily pretreated GCT patients was observed.
Authors: Christoph Oing; Winfried H Alsdorf; Gunhild von Amsberg; Karin Oechsle; Carsten Bokemeyer Journal: World J Urol Date: 2016-07-23 Impact factor: 4.226
Authors: Benjamin Carlisle; Nadine Demko; Georgina Freeman; Amanda Hakala; Nathalie MacKinnon; Tim Ramsay; Spencer Hey; Alex John London; Jonathan Kimmelman Journal: J Natl Cancer Inst Date: 2015-11-07 Impact factor: 13.506