Second malignancies after ewing tumor treatment in 690 patients from a cooperative German/Austrian/Dutch study.
BACKGROUND
Ewing tumor treatment involves high cumulative doses of alkylating agents and topoisomerase inhibitors, drugs capable of inducing second cancers. We analyzed the second cancer risk in a large cohort of consistently treated patients.


METHODS
Six hundred ninety Ewing tumor patients were treated between 1992 and 1999 with local therapy and vincristine. doxorubicin, ifosfamide and/or cyclophosphamide, and antinomycin D, with or without etoposide as a randomized question. Second cancer incidences were estimated by competing risk analyses; standardized incidence ratios (SIR) in comparison to registry data were compiled.


RESULTS
After a median observation time of 56 months (32 months for survivors), 6 of 690 patients had developed second cancers: MDS/AML, two, ALL/NHL, two, squamous cell carcinoma, one, liposarcoma, one. SIR were increased 20-30 fold in comparison to the general population. The cumulative second cancer risk five years after diagnosis of the Ewing tumor was 0.0093 for the total group, zero for patients without etoposide, and 0.0118 with etoposide. Additional phase II high-dose therapy increased the risk to 0.0398 after five years.


CONCLUSIONS
The second cancder risk observed was in the range to be expected in cancer survivors. High-dose therapy, and less markedly, etoposide, may contribute to the overall second cancer risk.
Paulussen
M
M
Department of Pediatric Hematology/Oncology, University of Münster Germany. michael.paulussen@uni-muenster.de
Ahrens
S
S
Lehnert
M
M
Taeger
D
D
Hense
H W
HW
Wagner
A
A
Dunst
J
J
Harms
D
D
Reiter
A
A
Henze
G
G
Niemeyer
C
C
Göbel
U
U
Kremens
B
B
Fölsch
U R
UR
Aulitzky
W E
WE
Voûte
P A
PA
Zoubek
A
A
Jürgens
H
H
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003609:Dactinomycin / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005060:Europe; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D015994:Incidence; D007223:Infant; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced*; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012512:Sarcoma, Ewing / Q000188:drug therapy*; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D007069:Ifosfamide