Source: DGNews  |  Posted 3 years ago

By Cameron Johnston

CHICAGO -- June 1, 2008 -- Patients with localised Ewing's sarcoma who receive chemotherapy in 14-day cycles have better outcomes than those receiving the same chemotherapy in 21-day cycles, according to researchers here at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting.

Richard B. Womer, MD, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, discussed the results of a trial conducted at 160 centres worldwide, in which 568 patients with Ewing's sarcoma, not previously treated, received a modified chemotherapy cycle that began every 14 days or when a patient's absolute neutrophil count was over 750 cells/mm³ and platelet count was over 75 x 109/L. The median interval between chemotherapy in this group was 15 days (mean 18.5 days), compared to the median interval for the standard chemotherapy, which was 21 days (mean 23.3 days).

Patients on the intensive every-2-weeks regimen (n = 284) experienced significantly longer event-free survival and no increase in toxicities compared with patients who received the same chemotherapy in the standard cycles beginning every 21 days (n = 284), Dr. Womer said in a presentation here on May 31.

Chemotherapy for Ewing's sarcoma traditionally has been vincristine (2 mg/m²), doxorubicin (75 mg/m²), and cyclophosphamide (1.2 g/m²). Dr. Womer noted, however, that it was felt that the standard therapy could be improved upon by adding either etoposide or ifosfamide to the regimen and that further improvements might be realised if the dosing cycle could be shortened.

Patients in this study, who were all under the age of 50 years, received the vincristine, doxorubicin, and cyclophosphamide combination, and alternated between receiving ifosfamide (9 g/m²) or etoposide (100 mg/m²) on each of 14 total cycles.

Supportive care was given in the form of the granulocyte-colony stimulating factor filgrastim (5 mg/kg/day, maximum 300 mg).

Patients in this study also received primary tumour treatment with either radiation therapy, surgery, or both, beginning 13 weeks into the trial (after 4 cycles in the standard-cycle group and 6 cycles in the intensive-cycle group).

The 4-year, event-free survival (median 3 years) was 76% for patients who were in the intensive-cycle arm and 65% for those patients in the standard-cycle arm.

There was no difference between the 2 groups in terms of toxicities or adverse events. Fever and low white blood cell count occurred in 7% of patients in the intensive-cycle arm, compared with 6% in the standard-cycle arm. Infections and secondary malignant neoplasms, which would lead to an increased number of days in hospital, were likewise similar. There was 1 death recorded in the intensive-cycle arm.

"We were gratified to learn that the toxicity did not increase as we decreased the time between therapy," Dr. Womer said.

There are limitations to this trial, however. Dr. Womer noted that this is the first study to investigate the intensive cycle time. Also, Dr. Womer concluded, "We don't know what the impact will be on patients who have metastatic disease at the time of diagnosis. Those with metastatic disease at the time of diagnosis have been much more difficult to treat."

Standard therapy in Europe already includes both ifosfamide and etoposide together, without alternating the 2 drugs, and without filgrastim support.

Ewing's sarcoma is a relatively rare form of bone cancer, which affects only around 5 to 6 patients per million during adolescence, and even fewer young children.

[Presentation title: Randomized Comparison of Every-Two-Week Versus Every-Three-Week Chemotherapy in Ewing Sarcoma Family Tumors (ESFT). Abstract 10504]