Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-E.W.I.N.G. 99 clinical trial.
BACKGROUND
The EUROpean Ewing tumour Working Initiative of National Groups 1999 (EURO-E.W.I.N.G. 99) protocol prescribes six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) as intensive induction chemotherapy for Ewing tumors (ET). Granulocyte-colony stimulating factor (G-CSF) is recommended. Adverse reactions (AR) were evaluated; quality assurance of data collection reviewed.


METHODS
Safety data from 4,746 courses of VIDE in 851 patients less than 50 years with ET were collected using a checklist and evaluated using descriptive statistics with sub-groups including gender, age, and tumor volume, analyzed by Wilcoxon and Kruskal-Wallis tests.


RESULTS
Myelosuppression and infections were the major AR but with appropriate supportive therapy targeted dose intensity was maintained. Five VIDE-related deaths with three due to sepsis were reported. Renal and cardiac toxicity were reflected by glomerular filtration rate (GFR) <39 ml/min/1.73 m2 in 0.1%, tubular phosphate reabsorption < or = 0.80 in 1.9%, and left ventricular shortening fracture <28% in 2.5% VIDE courses. Statistically significant gender-associated AR concerning hemoglobin and platelets were observed with females > males as were age-associated AR concerning hemoglobin, WBC, platelets, stomatitis, and vomiting with AR decreasing with age, that is, children > adolescents > adults. No association of AR to tumor volume was found. In VIDE courses with and without G-CSF, neutropenia-related fever in 60.8% and 65.8%, and infection in 54.7% and 61.0% courses, respectively, were recorded.


CONCLUSIONS
AR under VIDE remained within the expected range. Some AR, for example, hematotoxicity were significantly influenced by age and gender but not by tumor volume. G-CSF did not significantly influence neutropenia-related fever and infection. Solicited safety collection with checklists adequately reflects the burden per course.
Juergens
Christine
C
Coordinating Centre for Clinical Trials (KKS), University of Muenster, Muenster, Germany.
Weston
Claire
C
Lewis
Ian
I
Whelan
Jeremy
J
Paulussen
Michael
M
Oberlin
Odile
O
Michon
Jean
J
Zoubek
Andreas
A
Juergens
Herbert
H
Craft
Alan
A
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D002986:Clinical Trials as Topic; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012512:Sarcoma, Ewing / Q000188:drug therapy*; D018709:Statistics, Nonparametric; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D007069:Ifosfamide