Compressed chemotherapy intervals effective in Ewing’s sarcoma
Patients with localized Ewing’s sarcoma who underwent chemotherapy administered every 2 weeks experienced superior outcomes compared with those who underwent chemotherapy every 3 weeks, according to study results.
The compressed interval was not associated with increased toxicity, the researchers wrote.
Clinicians frequently treat Ewing’s sarcoma with alternating vincristine-doxorubicin-cyclophosphamide (VDC) and ifosfamide-etoposide (IE) cycles, along with chemotherapy and surgery or radiation. New, effective drugs for Ewing’s sarcoma remain elusive. Because of this, researchers have focused on improving outcomes by increasing the doses given or decreasing the intervals between doses, according to background information in the study.
Richard B. Womer
In the current study, Richard B. Womer, MD, professor of pediatrics in the division of oncology at the University of Pennsylvania School of Medicine, and colleagues examined whether chemotherapy intensification through interval compression could improve the outcome of patients with localized Ewing’s sarcoma.
Womer and colleagues randomly assigned 568 newly diagnosed Ewing’s sarcoma patients aged 50 years or younger to standard treatment (n=284) or the intensified regimen (n=284).
Patients in the standard cohort began chemotherapy cycles every 21 days compared with the intensified cohort, which began cycles every 14 days.
Patients in the intensified arm received 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 filgrastim (5 mg/kg per day).
Primary tumor treatment began at week 13 (after four cycles in the standard arm or six cycles in the intensified arm).
Event-free survival (EFS) served as the primary endpoint.
The median cycle interval for standard treatment was 21 days (mean=22.45 days). For intensified treatment, the median interval was 15 days (mean=17.29 days).
Researchers analyzed 2,897 standard cycles and 2,862 intensified cycles. The mean cycle durations were 22.45 ± 4.87 days for standard treatment and 17.29 ± 5.4 days for intensified treatment (P<.001).
At a median 5 years, EFS was 65% among patients in the standard arm and 73% among patients in the intensified treatment arm (P=.48). This represented a 22% decrease in the risk of recurrence, Womer and colleagues wrote.
OS was 83% among patients in the intensified treatment arm (HR=0.69; 95% CI, 0.47-1.00) and 77% among patients in the standard arm (P=.056), a difference that just missed being statistically significant, according to the researchers.
EFS at 5 years was considerably worse for patients aged 18 years or older (47%) compared with patients aged younger than 18 years (72%; P<.001), according to study results.
In the intensified cohort, one patient developed colitis and sepsis while neutropenic and died. Sixteen patients developed second malignancies. Of them, nine were assigned to the standard arm and seven were assigned to the intensified treatment arm (P=.62).
Researchers observed similar toxicities between the two arms. Patients in the standard cohort had a mean of 5 ± 4.25 hospital days per cycle, compared with a mean of 5.1 ± 4.26 hospital days for patients in the intensified treatment arm (P=.43).
“These results demonstrate that reducing the interval between chemotherapy cycles from 3 weeks to 2 weeks using filgrastim improves the efficacy of treatment in patients with localized Ewing’s sarcoma family tumors,” Womer and colleagues wrote. “This could have implications for treatment of other childhood malignancies and other sarcomas in all ages.”
Disclosure: The researchers report no relevant financial disclosures.