Intensive alternating 6-drug chemotherapy for high-risk nonmetastatic rhabdomyosarcoma in children and adolescents: Impact on survival.

Abstract

9566 Background: Both 5-year overall survival (OS) and event free survival (EFS) for pediatric rhabdomyosarcoma (RMS) has increased in the last 3 decades through multimodality, risk-adapted management. The reported EFS for high risk RMS in children treated at the NCI in Egypt during the 1990s was 50%. Using an intensive 6 drug alternating chemotherapy regimen in addition to local control measures was our aim to improve the outcome for this group of patients. Methods: Forty-six previously untreated patients, younger than 21 years of age, with localized high risk RMS received this regimen. High risk criteria included: (1) Localized tumors (T1) biopsied or incompletely resected, ortumors extending beyond the tissue or organ of origin (T2) completely or incompletely resected at any site (excluding orbit, uterus, vagina, and paratestis); (2)All node positive patients with primary tumor at any site; and (3) All RMS with alveolar histology at any site. Chemotherapy regimen comprised 27 weeks of alternating 6 drugs (carboplatin, doxorubicin hydrochloride, ifosfamide, actinomycin D, etoposide, vincristine). Local therapy (surgery, radiotherapy, or both) was offered at week 9. Results: Forty-six patients meeting high-risk criteria were recruited from September 2000 to November 2005. Median follow-up of survivors was 62 months. The 5-year OS and EFS for the whole group was 64% ± 10% and 47% ± 8% respectively. The EFS was significantly affected by: the size of the tumor (≤5 cm vs. > 5 cm, p= 0.03), SIOP UICC clinical stage (p = 0.004), IRS stage (p = 0.01), lymph node status (p = 0.02), surgery vs. incisional biopsy (p=0.01) and overall duration of time in which therapy was delivered (p = 0.04). There was significant toxicity, mainly hematologic, but only one treatment related fatality. Conclusions: The use of intensified alternating 6-drug CT did not improve the EFS compared with historical control although it was feasible to be delivered safely in a variety of outpatient settings. Surgical resection of the tumor is essential. Delivering therapy in a timely fashion appears to impact outcome and future investigations will focus on impediments to administering chemotherapy as scheduled.