Metformin as Maintenance Therapy in Patients With Bone Sarcoma and High Risk of Relapse

Summary

Primitive bone sarcoma are rare tumors with low options of therapy for patient treatment. 1. OSTEOSARCOMA VERY POOR RESPONDER COHORT. Necrosis on primitive localized osteosarcoma represents one of the principal prognostic factors. Nowadays, for localized osteosarcoma there is no maintenance therapy that have shown to be effective. In ISG-OS1 study in patients with necrosis \< 60% had an event free survival (EFS) at 3 yrs of 20% (Ferrari S ) in a more recent analysis (Tsuda Y 2020) patients with a necrosis \<60% had a 3 y EFS of 35% . 2. OSTEOSARCOMA AND EWING'S SARCOMA AFTER FIRST RELAPSE Maintenance therapy after Complete Remission occurring after Ewing's sarcoma or osteosarcoma patients is not a standard rule. These patients when free from disease, after first relapse, are more likely to face a second relapse. EFS at ONE YEAR after first relapse in osteosarcoma is shown in literature to be around 21% (Leary SE 2013) and 16% (Tirtei E 2017). The EFS at ONE YEAR after first relapse in Ewing's sarcoma is inferior to 20% (Barker 2005, Ferrari S 2015). A maintenance therapy with low toxicity in these high risk patients could be an option. Metformin has been reported to a reduce the incidence of different type of cancer in diabetic patients. Metformin is well tolerated in diabetics an it is used in other conditions in non diabetic, as ovarian polycystic syndrome, metabolic syndrome and obesity. Metformin has been employed as chemoprevention related to its mechanism of action in breast cancer (NCT01101438 ) and in pediatric cancer together with chemotherapy (NCT01528046). This study aim to explore the effectiveness of metformin (a low cost and well tolerated drug) as maintenance therapy in osteosarcoma and Ewing sarcoma patients at high risk of relapse.

Timeline

Start

2021-03-01

Primary completion

2027-07

Completion

2027-07

Publications

• Background Ferrari S, Bacci G, Picci P, Mercuri M, Briccoli A, Pinto D, Gasbarrini A, Tienghi A, Brach del Prever A. Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy. Ann Oncol. 1997 Aug;8(8):765-71. doi: 10.1023/a:1008221713505.
• Background Leary SE, Wozniak AW, Billups CA, Wu J, McPherson V, Neel MD, Rao BN, Daw NC. Survival of pediatric patients after relapsed osteosarcoma: the St. Jude Children's Research Hospital experience. Cancer. 2013 Jul 15;119(14):2645-53. doi: 10.1002/cncr.28111. Epub 2013 Apr 26.
• Background Barker LM, Pendergrass TW, Sanders JE, Hawkins DS. Survival after recurrence of Ewing's sarcoma family of tumors. J Clin Oncol. 2005 Jul 1;23(19):4354-62. doi: 10.1200/JCO.2005.05.105. Epub 2005 Mar 21.
• Background Ferrari S, Luksch R, Hall KS, Fagioli F, Prete A, Tamburini A, Tienghi A, DiGirolamo S, Paioli A, Abate ME, Podda M, Cammelli S, Eriksson M, Brach del Prever A. Post-relapse survival in patients with Ewing sarcoma. Pediatr Blood Cancer. 2015 Jun;62(6):994-9. doi: 10.1002/pbc.25388. Epub 2015 Jan 13.
• Background Tsuda Y, Tsoi K, Parry MC, Stevenson JD, Fujiwara T, Sumathi V, Jeys LM. Impact of chemotherapy-induced necrosis on event-free and overall survival after preoperative MAP chemotherapy in patients with primary high-grade localized osteosarcoma. Bone Joint J. 2020 Jun;102-B(6):795-803. doi: 10.1302/0301-620X.102B6.BJJ-2019-1307.R1.

Drugs

Indications