Intermediate-risk rhabdomyosarcoma (RMS) is:
- Non-metastatic (Group I-III) alveolar (RMS) arising at any site (Stage 1-3)
- Incompletely excised (Group III) embryonal RMS arising in an unfavorable site (Stage 2,3).
The long-term failure-free survival (FFS) for intermediate-risk RMS, as defined above, is still only 65%.
To improve long-term survival, the COG research study ARST0531 compared standard VAC chemotherapy versus VAC alternating with vincristine and irinotecan (VI). RT (36-50.4Gy) began at week 4 in conjunction with VI to determine the potential benefit of early local therapy in this group of patients. The outcome of patients randomly assigned to either standard vincristine,dactinomycin, and cyclophosphamide (VAC) chemotherapy or VAC alternating with vincristine and irinotecan (VI) was compared.
- The cumulative dose of cyclophosphamide in the VAC arm of this study was lower than the previous IRS-III and IV studies (16.8 g/m2 vs 23.4g/m2 and 26.4g/m2 respectively). It was unknown whether this would affect survival or acute and chronic toxicity related to this drug.
- RT started early at Week 4 (compared to week 13 in the low risk study) for most all patients.
- The long-term morbidity of RT or aggressive surgery for very young (≤ 24 months old) children makes local control very challenging. The COG study permitted deviations at the discretion of the treating clinicians in these very young patients.
- Guidelines for GTV, CTV and PTV were the same as low risk protocol. Preliminary results are published in abstract form. With a median follow-up of 2.46 years in surviving patients, the addition of VI to did not significantly improve EFS or OS compared to VAC alone.
- EFS at 2 years was 64% in both groups. OS at 2 years was 86% in the VAC/VI group compared to 84% in the VAC group.
- There was a lower rate of hematologic toxicity and cumulative cyclophosphamide dose with VAC/VI (8.4 g/m2 vs 16.8 g/m2). There was less diarrhea in patients treated with VAC alone. VAC/VI may serve as a standard arm in future intermediate risk RMS trials.
The current COG protocol (ARST1431) will attempt to improve long-term survival for patients with IR RMS. This study will compare VAC/VI with VAC/VI plus temsirolimus (an mTOR inhibitor with demonstrated activity in patients with relapsed rhabdomyosarcoma). Radiotherapy will start at weak 13. This study is open to accrual.
Clinical Group and required RT Total Dose:
|Clinical Group||Total Dose|
Alveolar only 36 Gy
|II||Node negative 36 Gy|
|II||Node positive 41.4 Gy|
|III||Alveolar, orbit only 45 Gy|
|III||all other sites 50.4 Gy|