Interval-compressed Chemotherapy More Effective with No Increase in Toxicity

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A randomized controlled trial among patients with newly diagnosed localized Ewing sarcoma found that “chemotherapy administered every 2 weeks is more effective than chemotherapy administered every 3 weeks, with no increase in toxicity,” investigators from the Children’s Oncology Group reported in the Journal of Clinical Oncology. At 5 years, event-free survival, the primary endpoint of the trial, was 73% for patients receiving chemotherapy every 2 weeks, compared with 65% for patients receiving chemotherapy every 3 weeks (P = .048). This translates to a 22% decrease in risk of recurrence, the researchers noted.

Overall survival was 83% for patients in the 2-week group vs 77% for those in the 3-week group. “The superiority of the intensified arm in overall survival just misses conventional statistical significance (P =.056); although relapsed Ewing sarcoma is rarely cured, patients often survive from several months to a few years after relapse, causing survival to lag behind [event-free survival],” the researchers added.

“In the absence of new effective agents for Ewing sarcoma, the Children’s Oncology Group focused on improving outcome by increasing chemotherapy dose-intensity,” the investigators explained. Patients received a regimen of vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1.2 g/m2) alternating with ifosfamide (9 g/m2) and etoposide (500 mg/m2) for 14 cycles, with the cycles to start every 14 or 21 days provided patients had an absolute neutrophil count greater than 750 × 106/L and a platelet count greater than 75 × 109/L. Between cycles, patients received filgrastim (Neupogen, 5 mg/kg/d; maximum, 300 mg).

“Primary tumor treatment (surgery, radiation, or both) was to begin at week 13 (after four cycles in the standard arm and six cycles in the intensified arm),” the authors explained. Each arm had 284 patients. “The primary site could be bone or soft tissue, but not intradural soft tissues,” according to the eligibility criteria, and patients could have no evidence of metastatic disease.

“The use of filgrastim in our study was critical,” the researchers reported. “Pegylated filgrastim (pegfilgrastim [Neulasta]) came to market shortly before this study opened. Although it offers the advantage of a single injection rather than a series of 10 to 14 daily injections, we forbade its use because of a lack of experience with either interval compression or children. It now seems that pegfilgrastim also permits interval compression with similar effectiveness to filgrastim in children.” ■

Womer RB, et al: J Clin Oncol 30:4148-4154, 2012.




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