Back to Search
Start Over
Phase 2 study for nonmetastatic extremity high-grade osteosarcoma in pediatric and adolescent and young adult patients with a risk-adapted strategy based on ABCB1/P-glycoprotein expression: An Italian Sarcoma Group trial (ISG/OS-2)
- Publication Year :
- 2022
- Publisher :
- John Wiley and Sons Inc, 2022.
-
Abstract
- Background: According to retrospective osteosarcoma series, ABCB1/P-glycoprotein (Pgp) overexpression predicts for poor outcomes. A prospective trial to assess a risk-adapted treatment strategy using mifamurtide in Pgp+ patients was performed. Methods: This was a phase 2, multicenter, uncontrolled trial including patients 40 years old or younger with nonmetastatic extremity high-grade osteosarcoma stratified according to Pgp expression. All patients received high-dose methotrexate, doxorubicin, and cisplatin (MAP) preoperatively. In Pgp+ patients, mifamurtide was added postoperatively and combined with MAP for a good histologic response (necrosis ≥ 90%; good responders [GRs]) or with high-dose ifosfamide (HDIFO) at 3 g/m2/d on days 1 to 5 for a histologic response < 90% (poor responders [PRs]). Pgp– patients received MAP postoperatively. After an amendment, the cumulative dose of methotrexate was increased from 60 to 120 g/m2 (from 5 to 10 courses). The primary end point was event-free survival (EFS). A postamendment analysis was performed. Results: In all, 279 patients were recruited, and 194 were included in the postamendment analysis: 70 (36%) were Pgp–, and 124 (64%) were Pgp+. The median follow-up was 51 months. For Pgp+ patients, 5-year EFS after definitive surgery (null hypothesis, 40%) was 69.8% (90% confidence interval [CI], 62.2%-76.2%): 59.8% in PRs and 83.7% in GRs. For Pgp– patients, the 5-year EFS rate was 66.4% (90% CI, 55.6%-75.1%). Conclusions: This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study.
- Subjects :
- Adult
Cancer Research
ATP Binding Cassette Transporter, Subfamily B
ATP binding cassette subfamily B member 1 (ABCB1)
P-glycoprotein
adolescents and young adults (AYAs)
chemotherapy
high-grade bone sarcoma
mifamurtide
osteosarcoma
pediatric bone tumors
Adolescent
Antineoplastic Combined Chemotherapy Protocols
Child
Disease-Free Survival
Extremities
Humans
Ifosfamide
Italy
Methotrexate
Prospective Studies
Retrospective Studies
Treatment Outcome
Young Adult
Bone Neoplasms
Osteosarcoma
Settore MED/06 - Oncologia Medica
ATP Binding Cassette Transporter
Oncology
Subfamily B
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....72d00a2c17d3b64de959c8f1905780c6