Outcome after reduced chemotherapy for intermediate-risk neuroblastoma.
BACKGROUND
The survival rate among patients with intermediate-risk neuroblastoma who receive dose-intensive chemotherapy is excellent, but the survival rate among patients who receive reduced doses of chemotherapy for shorter periods of time is not known.


METHODS
We conducted a prospective, phase 3, nonrandomized trial to determine whether a 3-year estimated overall survival of more than 90% could be maintained with reductions in the duration of therapy and drug doses, using a tumor biology-based therapy assignment. Eligible patients had newly diagnosed, intermediate-risk neuroblastoma without MYCN amplification; these patients included infants (<365 days of age) who had stage 3 or 4 disease, children (≥365 days of age) who had stage 3 tumors with favorable histopathological features, and infants who had stage 4S disease with a diploid DNA index or unfavorable histopathological features. Patients who had disease with favorable histopathological features and hyperdiploidy were assigned to four cycles of chemotherapy, and those with an incomplete response or either unfavorable feature were assigned to eight cycles.


RESULTS
Between 1997 and 2005, a total of 479 eligible patients were enrolled in this trial (270 patients with stage 3 disease, 178 with stage 4 disease, and 31 with stage 4S disease). A total of 323 patients had tumors with favorable biologic features, and 141 had tumors with unfavorable biologic features. Ploidy, but not histopathological features, was significantly predictive of the outcome. Severe adverse events without disease progression occurred in 10 patients (2.1%), including secondary leukemia (in 3 patients), death from infection (in 3 patients), and death at surgery (in 4 patients). The 3-year estimate (±SE) of overall survival for the entire group was 96±1%, with an overall survival rate of 98±1% among patients who had tumors with favorable biologic features and 93±2% among patients who had tumors with unfavorable biologic features.


CONCLUSIONS
A very high rate of survival among patients with intermediate-risk neuroblastoma was achieved with a biologically based treatment assignment involving a substantially reduced duration of chemotherapy and reduced doses of chemotherapeutic agents as compared with the regimens used in earlier trials. These data provide support for further reduction in chemotherapy with more refined risk stratification. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003093.)
Baker
David L
DL
Princess Margaret Hospital for Children, Perth, Australia.
Schmidt
Mary L
ML
Cohn
Susan L
SL
Maris
John M
JM
London
Wendy B
WB
Buxton
Allen
A
Stram
Daniel
D
Castleberry
Robert P
RP
Shimada
Hiroyuki
H
Sandler
Anthony
A
Shamberger
Robert C
RC
Look
A Thomas
AT
Reynolds
C Patrick
CP
Seeger
Robert C
RC
Matthay
Katherine K
KK
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D007223:Infant; D057194:Intention to Treat Analysis; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D016190:Carboplatin