Toxicity prevention with amifostine in pediatric osteosarcoma patients treated with cisplatin and doxorubicin.
Amifostine has emerged as a pancytoprotectant shown protection against nephrotoxicity, neurotoxicity and ototoxicity in preclinical studies.


METHODS
We designed a prospective comparative randomized trial to evaluate the cytoprotective effects of amifostine in patients with osteosarcoma receiving cisplatin and doxorrubicin. Patients were evaluated for renal, hearing and cardiac toxicity.


RESULTS
We included 28 patients, mean age was 11.6 years, five had metastatic disease. Fifteen patients received amifostine and 13 did not. 20% of patients receiving amifostine developed renal toxicity compared to 30% in the control group (p = 0.318). Grade 1 and 2 audiologic toxicity was present in 100% of the experimental group against 85% of the controls (p = 0.501). Grade 1 cardiac toxicity was present in 2 patients in the control group (p = 0.175). There were no statistical significant differences between the two groups for chemotherapy-related toxicity. Response to chemotherapy was significantly better in the amifostine group.


CONCLUSIONS
amifostine did not reduce the ototoxicity and nephrotoxicity of our treatment regime. It was not well tolerated due to emesis. It is a selective cytoprotectant without reducing the effect of chemotherapy.
Gallegos-Castorena
Sergio
S
Department of Pediatric Oncology, Hospital Infantil de Mexico Federico Gómez, Mexico, DF Mexico. galramos@prodigy.net.mx
Martínez-Avalos
Armando
A
Mohar-Betancourt
Alejandro
A
Guerrero-Avendaño
Guadalupe
G
Zapata-Tarrés
Martha
M
Medina-Sansón
Aurora
A
D000293:Adolescent; D004999:Amifostine / Q000009:adverse effects / Q000627:therapeutic use*; D000932:Antiemetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy*; D002125:Calcium Gluconate / Q000627:therapeutic use; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D034381:Hearing Loss / Q000139:chemically induced / Q000517:prevention & control*; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D006996:Hypocalcemia / Q000188:drug therapy / Q000517:prevention & control; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D020360:Neoadjuvant Therapy; D017294:Ondansetron / Q000627:therapeutic use; D012516:Osteosarcoma / Q000188:drug therapy* / Q000556:secondary; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
D000932:Antiemetics; D017294:Ondansetron; D004317:Doxorubicin; D004999:Amifostine; D002945:Cisplatin; D002125:Calcium Gluconate