Case Report Chemotherapy 2013;59:458–460 DOI: 10.1159/000365071
Received: February 27, 2014 Accepted after revision: May 20, 2014 Published online: August 22, 2014
Experience with Trabectedin in an Advanced Sarcoma Patient on Peritoneal Dialysis for End-Stage Renal Failure Maung Maung Myat Moe a Carlos Fernandez Teruel b Arturo Soto-Matos b a Oncology Department, Singleton Hospital, Swansea, UK; b Pharma Mar S.A. Sociedad Unipersonal, Colmenar Viejo, Spain
Key Words Advanced sarcoma · End-stage renal failure · Peritoneal dialysis · Trabectedin
Abstract Background: We wanted to evaluate the impact of peritoneal dialysis on trabectedin therapy in terms of side effects, response and levels in the blood and dialysate of a patient on peritoneal dialysis for end-stage renal failure caused by previous ifosfamide therapy. This has not yet been reported in the medical literature. Methods: We measured the levels of trabectedin in the blood and peritoneal dialysate at different time points before and after the administration of a 3rd cycle of trabectedin (1.5 mg/m2 over 24 h). Toxicity from the treatment was recorded and the response status was evaluated on a CT scan after the 3rd and 6th cycles. Results: Serum creatinine clearance (Cockcroft-Gault formula) was 8.31 ml/ min. The patient had a World Health Organization performance status score of ‘0’ and did not suffer any significant side effects except for grade 2 anaemia. There was no difference in the plasma level of trabectedin just before and after a 3-hour session of peritoneal dialysis. The amount of trabectedin in the peritoneal dialysates was undetectable (limit of quantification: 25.9 pg/ml). The patient achieved stable
© 2014 S. Karger AG, Basel 0009–3157/14/0596–0458$39.50/0 E-Mail [email protected] www.karger.com/che
disease after 3 cycles, and progressive disease was observed after 6 cycles on CT scan. Conclusion: Our patient did not suffer undue side effects from trabectedin, and peritoneal dialysis did not appear to have an impact on the clearance of the drug. © 2014 S. Karger AG, Basel
Introduction
Trabectedin (Yondelis; ET-743) is a natural marine product isolated from the Caribbean tunicate Ecteinascidia turbinata. Trabectedin covalently binds to the minor groove of deoxyribonucleic acid (DNA), bending the helix to the major groove. This binding to DNA triggers a cascade of events affecting several transcription factors, DNA binding proteins and DNA repair pathways, resulting in perturbation of the cell cycle [1]. Trabectedin is indicated for adult patients with advanced soft-tissue sarcoma, after the failure of anthracycline and ifosfamide or because they are not suited to receive these agents, and for advanced ovarian cancer in combination with pegylated doxorubicin [2]. The recommended dose is 1.5 mg/m2 of body surface area, administered as an intravenous infusion over 24 h once every 3 weeks. No dose adMaung Maung Myat Moe Oncology Department Singleton Hospital Swansea SA2 8QA (UK) E-Mail Maung.Moe @ nhs.net
justment is required for trabectedin monotherapy when creatinine clearance is >30 ml/min. However, no data are available for patients with a creatinine clearance
Received: February 27, 2014 Accepted after revision: May 20, 2014 Published online: August 22, 2014
Experience with Trabectedin in an Advanced Sarcoma Patient on Peritoneal Dialysis for End-Stage Renal Failure Maung Maung Myat Moe a Carlos Fernandez Teruel b Arturo Soto-Matos b a Oncology Department, Singleton Hospital, Swansea, UK; b Pharma Mar S.A. Sociedad Unipersonal, Colmenar Viejo, Spain
Key Words Advanced sarcoma · End-stage renal failure · Peritoneal dialysis · Trabectedin
Abstract Background: We wanted to evaluate the impact of peritoneal dialysis on trabectedin therapy in terms of side effects, response and levels in the blood and dialysate of a patient on peritoneal dialysis for end-stage renal failure caused by previous ifosfamide therapy. This has not yet been reported in the medical literature. Methods: We measured the levels of trabectedin in the blood and peritoneal dialysate at different time points before and after the administration of a 3rd cycle of trabectedin (1.5 mg/m2 over 24 h). Toxicity from the treatment was recorded and the response status was evaluated on a CT scan after the 3rd and 6th cycles. Results: Serum creatinine clearance (Cockcroft-Gault formula) was 8.31 ml/ min. The patient had a World Health Organization performance status score of ‘0’ and did not suffer any significant side effects except for grade 2 anaemia. There was no difference in the plasma level of trabectedin just before and after a 3-hour session of peritoneal dialysis. The amount of trabectedin in the peritoneal dialysates was undetectable (limit of quantification: 25.9 pg/ml). The patient achieved stable
© 2014 S. Karger AG, Basel 0009–3157/14/0596–0458$39.50/0 E-Mail [email protected] www.karger.com/che
disease after 3 cycles, and progressive disease was observed after 6 cycles on CT scan. Conclusion: Our patient did not suffer undue side effects from trabectedin, and peritoneal dialysis did not appear to have an impact on the clearance of the drug. © 2014 S. Karger AG, Basel
Introduction
Trabectedin (Yondelis; ET-743) is a natural marine product isolated from the Caribbean tunicate Ecteinascidia turbinata. Trabectedin covalently binds to the minor groove of deoxyribonucleic acid (DNA), bending the helix to the major groove. This binding to DNA triggers a cascade of events affecting several transcription factors, DNA binding proteins and DNA repair pathways, resulting in perturbation of the cell cycle [1]. Trabectedin is indicated for adult patients with advanced soft-tissue sarcoma, after the failure of anthracycline and ifosfamide or because they are not suited to receive these agents, and for advanced ovarian cancer in combination with pegylated doxorubicin [2]. The recommended dose is 1.5 mg/m2 of body surface area, administered as an intravenous infusion over 24 h once every 3 weeks. No dose adMaung Maung Myat Moe Oncology Department Singleton Hospital Swansea SA2 8QA (UK) E-Mail Maung.Moe @ nhs.net
justment is required for trabectedin monotherapy when creatinine clearance is >30 ml/min. However, no data are available for patients with a creatinine clearance
