ORAL PRESENTATION Lead Author: Richard B. Womer, MD
American Society for Clinical Oncology Annual Meeting
http://www.asco.org

SATURDAY, MAY 31, 3:00 PM (CDT) Children’s Hospital of Philadelphia
W375b Philadelphia, PA

Investigators from the Children’s Oncology Group (COG) have found for the first time that giving combination chemotherapy every two weeks is more effective than the same therapy given every three weeks in patients with Ewing’s sarcoma, without increasing side effects.

“These findings are convincing enough to change the standard of care for patients with localized Ewing’s sarcoma,” said lead author Richard B. Womer, MD, senior oncologist and professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine. “This study shows that progress against Ewing’s sarcoma can be made by giving commonly used anti-cancer drugs in new ways.”

Ewing’s sarcoma is a cancer that most often develops in the bones but can also form in soft tissue. It is generally diagnosed in children. Until this study, the standard treatment for this cancer included chemotherapy with the drugs vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide given every three weeks, as well as surgery and/or radiation therapy. With the development of better ways to bolster the immune and blood-forming systems of the body—enabling patients to tolerate more frequent chemotherapy—researchers seeking to improve treatments for several types of cancer have hypothesized that giving chemotherapy more frequently might be more effective than conventional approaches, without causing undue side effects.

In this study, researchers at 160 COG institutions sought to determine if giving the same five drugs every two weeks was more effective than giving them every three weeks in patients with Ewing’s sarcoma who were younger than 50 and had not yet had chemotherapy or radiation therapy. Primary treatment (surgery, radiation therapy, or both) began 13 weeks after chemotherapy was initiated. Event-free survival (the percentage of patients who did not die or experience a relapse or second cancer) was compared between 284 patients who received chemotherapy every two weeks and 284 who received the same regimen every three weeks. Patients in both groups received a total of 14 cycles of chemotherapy.

After a median follow-up of three years, event-free survival was 76 percent among the patients who received chemotherapy every other week, compared with 65 percent among those who received chemotherapy every three weeks. The incidence and severity of side effects remained similar between the two groups. Fever with low white blood cell count occurred in 7 percent
of those in the two-week arm and 6 percent of those in the three-week
arm; the incidence of infection was 4.8 percent and 4.6 percent,
respectively.

Abstract #10504

Randomized comparison of every-two-week v. every-three-week
chemotherapy in Ewing sarcoma family tumors (ESFT). R. B. Womer, D. C.
West, M. D. Krailo, P. S. Dickman, B. Pawel, E. for the Children's
Oncology Group AEWS0031 Committee

Background: Chemotherapy with
alternating cycles of vincristine-doxorubicin-cyclophosphamide and
ifosfamide-etoposide, and primary tumor treatment with surgery and/or
radiation therapy, is the usual approach to localized ESFT in North
America. We conducted a trial asking whether chemotherapy
intensification through interval compression could improve outcome.

Methods: This was a prospective
randomized-controlled trial for patients less than 50 y old with
extra-dural ESFT, without distant metastases or prior chemotherapy or
radiation therapy; and with adequate renal, cardiac, and hepatic
function. Patients were treated with vincristine (2 mg/sq.m, max. 2
mg), doxorubicin (75 mg/sq.m) and cyclophosphamide (1.2 g/sq.m)
alternating with ifosfamide (9 g/sq.m) and etoposide (100 mg/sq.m/),
for 14 cycles, with filgrastim (5 mg/kg/day, maximum 300 mg) between
cycles. Patients assigned to Regimen A were scheduled to begin
chemotherapy cycles every 21 days, and patients assigned to Regimen B
were scheduled to begin cycles every 14 days, or when ANC > 750 and
platelets > 75. Primary tumor treatment (surgery, radiation, or
both) was scheduled to begin week 13 (after 4 cycles in Regimen A and 6
cycles in Regimen B). The primary endpoint was event-free survival
using a two-sided log-rank test with size 0.05 and power 0.8 to detect
a 13% Embargoed Until May 15, 2008 at 9:00pm (EDT) 12 change in EFS
from 60%, with 264 patients in each arm.

Results: 587 patients were
enrolled and randomized, and 568 were eligible, 284 in each regimen.
For all courses, the median cycle interval for Regimen A was 21 days,
mean 23.3 days; in Regimen B, the median interval was 15 days, mean
18.5 days. Event-free survival at a median of 3 years was 65% in
Regimen A and 76% in Regimen B, p=0.028. The occurrence of specific
toxicities and the number of hospital days were similar for the two
regimens.

Conclusions: Every-2-week chemotherapy is more effective than every-three-week chemotherapy for localized ESFT, with no increase in toxicity.

Disclosures for Research Team: Nothing to disclose.