INT-0133
Osteosarcoma: a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate
N = 677
- Population
- Patients with osteosarcoma without clinically detectable metastatic disease (resectable disease per the 2008 report)
- Design
- 2 x 2 factorial randomisation to add or not add ifosfamide and/or liposomal muramyl tripeptide (MTP) to identical cumulative doses of cisplatin, doxorubicin and high-dose methotrexate, with definitive surgical resection of the primary tumour. 677 patients in the 2005 report; 662 patients in the 2008 reanalysis. Conducted by the Children's Oncology Group.
- Primary endpoint
- EFS, OS
- Arms
- Cisplatin, doxorubicin, high-dose methotrexate (control): Cisplatin, doxorubicin and high-dose methotrexate with definitive surgery
- Standard plus MTP (experimental): Standard chemotherapy plus liposomal muramyl tripeptide (MTP)
- Standard plus ifosfamide (experimental): Standard chemotherapy plus ifosfamide
- Standard plus ifosfamide and MTP (experimental): Standard chemotherapy plus ifosfamide and MTP
- People
- Meyers PA, Children's Oncology Group
Δ 36-month EFS−3 pointsOSHR 0.71 (95% CI 0.52–0.96)
Show the numbers
| Endpoint | Analysis | Standard plus MTP / Standard plus ifosfamide / Standard plus ifosfamide and MTP | Cisplatin, doxorubicin, high-dose methotrexate | Effect |
|---|---|---|---|---|
| EFSRandomised patients without clinically detectable metastatic disease (677) | primaryMeyers 2005 | 68% at 3 y | 71% at 3 y | 3-year EFS. The authors could not analyse by factorial design because they observed an interaction between ifosfamide and MTP; no hazard ratio or p-value is given in the abstract. |
| OSRandomised patients with resectable disease without clinically detectable metastases (662), MTP vs no MTP | long term-updateMeyers 2008 | — | — | HR 0.71 (95% CI 0.52–0.96)P=.03Reanalysis with 662 patients in which the authors found no interaction. 6-year OS rose from 70% without MTP to 78% with MTP (pooled across the ifosfamide arms). Ifosfamide did not improve EFS or OS; EFS showed a trend toward benefit with MTP (P = .08). |
| Endpoint | Analysis | Standard plus MTP / Standard plus ifosfamide / Standard plus ifosfamide and MTP | Cisplatin, doxorubicin, high-dose methotrexate | Effect |
|---|---|---|---|---|
| EFSRandomised patients without clinically detectable metastatic disease (677) | primaryMeyers 2005 | 68% at 3 y | 71% at 3 y | 3-year EFS. The authors could not analyse by factorial design because they observed an interaction between ifosfamide and MTP; no hazard ratio or p-value is given in the abstract. |
| OSRandomised patients with resectable disease without clinically detectable metastases (662), MTP vs no MTP | long term-updateMeyers 2008 | — | — | HR 0.71 (95% CI 0.52–0.96)P=.03Reanalysis with 662 patients in which the authors found no interaction. 6-year OS rose from 70% without MTP to 78% with MTP (pooled across the ifosfamide arms). Ifosfamide did not improve EFS or OS; EFS showed a trend toward benefit with MTP (P = .08). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.71 | 0.52–0.96 |
Appears in
Sources
Meyers PA, Schwartz CL, Krailo M, Kleinerman ES, Betcher D, Bernstein ML, et al. Osteosarcoma: a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate. J Clin Oncol. 2005;23(9):2004-11.
Meyers PA, Schwartz CL, Krailo MD, Healey JH, Bernstein ML, Betcher D, et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival--a report from the Children's Oncology Group. J Clin Oncol. 2008;26(4):633-8.