[Use of cyclosporin and verapamil in association with chemotherapy in the treatment of pediatric patients with advanced-stage neoplasms. A pilot study].
Multidrug resistance represents one of the most important factors that may lead to a therapeutic failure in some patients affected by malignancies. One of the best known mechanisms is linked to the genic amplification or the overproduction of a membrane glycoprotein, GP170, that is the product of the gene MDR1. The existence of drugs (calcium blockers, cyclosporine, tamoxifen, reserpine, quinidine) able to bind themselves to gp170 and to paralyze its activity in vitro is well known. We studied 20 pediatric patients (median age 9 years) affected by acute lymphoblastic leukemia (ALL), osteosarcoma, neuroblastoma and medulloblastoma, in advanced stage of disease. We employed in all cases the association of cytostatics with verapamil (50-70 mg/m2 i.v.) and cyclosporine (5-8 mg/kg i.v.) with different infusion schedules. In leukemias we administered vincristine (1.5 mg/m2), and daunomycin (40 mg/m2), in solid tumors VP16 (150 mg/m2) and adriamycin (60 mg/m2). Seventy-two therapeutic courses were performed: 39 in ALL, 16 in osteosarcoma, 16 in neuroblastoma and 1 in medulloblastoma. On the whole 5 complete remissions were achieved in ALL patients and 1 in an osteosarcoma patient. We did not observe a significant myelosuppression during treatment, therefore few infectious complications occurred; furthermore electrocardiographic changes have been mild and promptly resolved after temporary discontinuation of verapamil infusion. Our data suggest a synergy of verapamil and cyclosporine in the inhibition of multidrug resistance induced by gp170, without the occurrence of heavy toxicity. The results obtained in ALL patients are encouraging., especially in view of a possible subsequent bone marrow transplantation, while in solid tumors they are not as satisfying.
Miniero
R
R
Divisione di Pediatria Oncologica, Università degli Studi di Torino.
Massara
F M
FM
Saroglia
E M
EM
Soldano
S
S
Barisone
E
E
Leone
L
L
Arrighini
A
A
Andolina
M
M
Brach del Prever
A
A
Madon
E
E
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy; D002528:Cerebellar Neoplasms / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D003524:Cyclosporins / Q000008:administration & dosage*; D003630:Daunorubicin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D009447:Neuroblastoma / Q000188:drug therapy; D012516:Osteosarcoma / Q000188:drug therapy; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D014700:Verapamil / Q000008:administration & dosage*; D014750:Vincristine / Q000008:administration & dosage
D003524:Cyclosporins; D014750:Vincristine; D004317:Doxorubicin; D014700:Verapamil; D003630:Daunorubicin
Impiego della ciclosporina e del verapamile in associazione a chemioterapici nel trattamento di pazienti pediatrici con neoplasia in fase avanzata. Studio pilota.