Combined biodifferentiating and antiangiogenic oral metronomic therapy is feasible and effective in relapsed solid tumors in children: single-center pilot study.
BACKGROUND
To outline an outpatient-based treatment for children with relapsed solid tumors, who already have been extensively pretreated, we defined a 4-drug protocol named COMBAT (combined oral maintenance biodifferentiating and antiangiogenic therapy). Using this protocol, we performed a pilot study to determine its feasibility in children with relapsed and/or high-risk pediatric solid tumors.


METHODS
22 children received the COMBAT protocol. Treatment consisted of daily celecoxib administration along with daily 13-cisretinoic acid (2 weeks on / 2 weeks off) and cycles of metronomic temozolomide (90 mg/m2 for 42 days) and low-dose etoposide (21 days). The treatment was scheduled for a period of 1 year.


RESULTS
9 of the 14 patients assessable for response demonstrated evidence of treatment benefit manifested as prolonged disease stabilization or response. The protocol medication was well tolerated with very good compliance. Only minimal side effects where observed which responded to dose modification or local therapy.


CONCLUSIONS
The COMBAT regimen is well tolerated by patients with intensive prior therapy including myeloablative regimens. Favorable responses observed in this cohort of patients support the further exploration of this and/or similar strategies in the treatment of pediatric solid tumors.
Sterba
Jaroslav
J
Department of Pediatric Oncology, University Hospital Brno, Czech Republic. jsterb@fnbrno.cz
Valik
Dalibor
D
Mudry
Peter
P
Kepak
Tomas
T
Pavelka
Zdenek
Z
Bajciova
Viera
V
Zitterbart
Karel
K
Kadlecova
Vera
V
Mazanek
Pavel
P
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068579:Celecoxib; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy*; D010865:Pilot Projects; D011720:Pyrazoles / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D000077204:Temozolomide; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
D020533:Angiogenesis Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D014212:Tretinoin; D005047:Etoposide; D003606:Dacarbazine; D000068579:Celecoxib; D000077204:Temozolomide