Toxicity prevention with amifostine in pediatric osteosarcoma patients treated with cisplatin and doxorubicin

Pediatr Hematol Oncol. 2007 Sep;24(6):403-8. doi: 10.1080/08880010701451244.

Abstract

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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Amifostine / adverse effects
  • Amifostine / therapeutic use*
  • Antiemetics / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Neoplasms / drug therapy*
  • Calcium Gluconate / therapeutic use
  • Child
  • Cisplatin / administration & dosage
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Female
  • Hearing Loss / chemically induced
  • Hearing Loss / prevention & control*
  • Heart Diseases / chemically induced
  • Heart Diseases / prevention & control*
  • Humans
  • Hypocalcemia / drug therapy
  • Hypocalcemia / prevention & control
  • Infusions, Intra-Arterial
  • Infusions, Intravenous
  • Kidney Diseases / chemically induced
  • Kidney Diseases / prevention & control*
  • Male
  • Neoadjuvant Therapy
  • Ondansetron / therapeutic use
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / secondary
  • Prospective Studies
  • Severity of Illness Index
  • Treatment Outcome
  • Vomiting / chemically induced
  • Vomiting / prevention & control

Substances

  • Antiemetics
  • Ondansetron
  • Doxorubicin
  • Amifostine
  • Cisplatin
  • Calcium Gluconate