1520P - Development of a new promising rescue agent for high dose methotrexate (HDMTX) treatment in osteosarcoma - a safety and dose finding study

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cytotoxic agents
Bone Sarcomas
Sarcoma
Therapy
Biological therapy
Presenter Mikael Eriksson
Citation Annals of Oncology (2017) 28 (suppl_5): v521-v538. 10.1093/annonc/mdx387
Authors M. Eriksson1, M. Rychłowska-Pruszyńska2, M. Csoka3, E. Kabickova4, P. Mudry5
  • 1Skåne University Hospital, Department of Oncology, 221 85 - Lund/SE
  • 2Paediatric Surgical Oncology Clinic Warsaw, Institution of Mother and Child, 01-211 - Warsaw/PL
  • 32nd Department Of Paediatrics, Semmelweis University, 1085 - Budapest/HU
  • 4Department Of Paediatric Haematology And Oncology, Motol University Hospital, 150 06 - Prague/CZ
  • 5University Hospital Brno And School Of Medicine, Masaryk University, Department of Pediatric Oncology, 662 63 - Brno/CZ

Abstract

Background

HDMTX followed by calcium folinate (CF) rescue is established as part of MAP chemotherapy to manage toxicity during osteosarcoma treatment. A problem with HDTMX is the variability in plasma exposure of both MTX and CF leading to an unpredictable response. A potentially superior rescue agent methylenetetrahydrofolate (Modufolin®), containing the active metabolite of CF, has been evaluated to identify a safe and effective dose for further development.

Methods

This exploratory study performed in Hungary, Poland, Sweden and Czechia involved osteosarcoma patients, 12-40 years, planned for MAP chemotherapy. All patients received one MAP cycle (two HDMTX courses) with standard CF rescue of 15 mg/m2. Those that completed this MAP cycle successfully according to six defined criteria subsequently received Modufolin® in the following cycle (two HDMTX courses). There were two Modufolin® dose cohorts, 15 mg/m2 (1) and 7.5 mg/m2 (2). A Data and Safety Monitoring Board evaluated safety before initiation of the second dose cohort and suggested the dose for further development.

Results

Eight patients 12-17 years were included. Four patients were treated in cohort 1 and four in cohort 2. In cohort 1, no MTX toxicity or delayed elimination with subsequent treatment delay was reported. In cohort 2 one patient reported mucositis grade 3 and failed successful advancement after first course of Modufolin®. In both cohorts and after both types of rescue, there were cases with significantly increased s-creatinine levels.

Conclusions

Modufolin® seems to be a safe and effective rescue agent after HDMTX. The study design however precludes a comparison between Modufolin® and CF, since only patients with successful CF rescue received Modufolin®. The higher dose of 15 mg/m2 seemed more effective as rescue and was selected for further development.

Clinical trial identification

EudraCT Nr 2013-001280-23

Legal entity responsible for the study

Isofol Medical AB

Funding

Isofol Medical AB

Disclosure

All authors have declared no conflicts of interest.