Late side effects of osteosarcoma neoadjuvant chemotherapy: The experience at Rizzoli institute

9508 Background: Good cure rate has been reached in osteosarcoma treatment with chemotherapy, but there are late side effects. Methods: We reviewed charts of 755 patients (pts) with localized osteosarcoma of the extremity treated in 6 subsequent protocols (1983–2000) with Doxorubicin (300–480 mg/m2), Cisplatin (300–600 mg/m2), Methotrexate (3.7–75 g/m2), Ifosfamide (30–75 g/m2). Etoposide was employed only in 47 pts. Results: With a median follow up of 8 yrs (5–20), the median 10-yrs EFS was 58%. 13 patients (1.7%), 9 females and 4 males, had a symptomatic cardiopathy with two cardiopathy-related deaths, and 3 patients needed a heart transplant. The median age of these pts was 13 yrs (4–28). Median Doxorubicine dose = 480 mg/m2. Median interval from chemotherapy completion to cardiopathy onset was 3 months; 7 patients are alive, and 6 died: 4 for cardiopathy, 2 for metastatic disease. 17 second malignant neoplasms (SMN) occurred in 16 pts (2.1%) after a median interval of 7 yrs. One patient had both a breast and ovarian cancer. SMN were: 2 AML, 3 ALL, 1 CML, 3 breast cancer, 1 CNS tumor, 1 lung tumor, 1 parotid tumor, 2 soft tissue sarcoma, 1 skin cancer, 1 ovary cancer, 1 Ewing sarcoma. Eight of these 16 pts died of the second tumor. Infertility related to chemotherapy affected mostly males. Amenorrhea affected 69% of postpubertal females during chemotherapy but only two pts had permanent amenorrhea (39 and 43 yrs). No delay in pubertal maturation was seen in both gender. The incidence of infertility in male was related to Ifosfamide and was dose-dependent. Permanent azoospermia was 100% in males who received 60–75g/m2 Ifosfamide. No congenital defects were observed in the offsprings of both gender. The incidence of chronic renal failure was negligible in pts who received 2 Ifosfamide; in those who received >60 g/m2 a subclinical tubular impairment was observed in 48%, but only 1pt required dialysis. In the last protocol, a mild hearing impairment due to Cisplatin was evident in 40% of pts. Conclusions: Late toxicities are relevant and prolonged follow-ups are recommended as well as less toxic protocols. No significant financial relationships to disclose.