Abstract 52P
Background
To improve outcomes for patients with Ewing sarcoma, the Ewing Family of Tumors (EFT) regimen was developed as a further dose intensification of the Memorial Sloan Kettering Cancer Center (MSKCC) P6 regimen, increasing the cumulative dose of ifosfamide from 27 g/m2 to 42 g/m2. We assessed the long-term outcomes of patients treated with both regimens to determine both the long-term safety and efficacy of ifosfamide dose intensification.
Methods
The regimens are described in the table. A retrospective chart review of newly diagnosed patients with localized Ewing sarcoma treated with the EFT regimen at MSKCC from 2003 – 2011 was conducted and compared to long term outcomes of patients treated on a prospective trial utilizing the P6 regimen enrolled from 1991 to 2001.
Results
A total of 44 patients (median age=17, range 3-33 years) were treated with P6 and 52 patients treated with EFT (median age=19, range <1-40 years). The median follow up duration for P6 was 23.5 years (range 1-32 years) and 12.3 years for EFT (range <1-19 years). There was no difference in overall survival (OS) between EFT and P6 (p=0.697), with a 10-year OS of 81.6% (95% CI: 66.5-90.3) for P6 and 78.1% (95% CI: 63.9-87.2) for EFT. The combined 10-year OS for patients on both regimens was 79.7% (95% CI: 70.0-86.5). There was no difference in time to recurrence, with median time to recurrence of 3.7 and 1.5 years for P6 and EFT respectively (p=0.097). There was no difference in the cumulative incidence (CI) of secondary neoplasms between the two regimens (p=-0.68), with a 10-year CI of 7.2% (95% CI: 63.9-87.2) for P6 and 2.3% (95% CI: 0.1-15.1) for EFT. Table: 52P
P6/EFT regimen chemotherapy
| 7 cycles, planned every 21 days | ||
| Cycles 1, 2, 3, 7: CAV | ||
| Day 1, 2 | Cyclophosphamide2,1 g/m2/day | Doxorubicin37.5 mg/m2/day |
| Day 1 only | Vincristine - 2 mg/m2 (max 2 mg) | |
| Cycles 4, 5, 6: IE | ||
| Days 1, 2, 3, 4, 5 | IfosfamideP6 = 1.8 g/m2/day, EFT = 2.8 g/m2/day | Etoposide100 mg/m2/day |
Conclusions
Ifosfamide dose intensification failed to improve outcomes for patients with localized Ewing sarcoma. Outcomes reported for either regimen are comparable in efficacy to interval dose compressed chemotherapy and 7 weeks shorter, making P6/EFT an attractive backbone for future trials looking to incorporate maintenance therapies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
W.D. Tap: Financial Interests, Personal, Advisory Board: Eli Lilly, EMD Serono, Mundipharma, C4 Therapeutics, Daiichi Sankyo, Deciphera; Financial Interests, Personal, Advisory Role: Adcendo, Amgen. All other authors have declared no conflicts of interest.