Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities. Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin

Abstract

Background. Neoadjuvant chemotherapy is the most accepted treatment for localized osteosarcoma. This has led to a great improvement in limb‐sparing surgery and in disease‐free survival. Patients with a good response to preoperative chemotherapy showed a higher disease‐free survival rate. Current studies examine the possibility of patients whose limbs could be rescued with a poor necrosis and a reduction of the side effects related to aggressive treatments. Methods. Between September 1986 and December 1989, 164 patients entered the second neoadjuvant study conducted at the Rizzoli Institute, Bologna, Italy, for non‐metastatic osteosarcoma of the extremities. Preoperative chemotherapy consisted of two cycles of high‐dose methotrexate intravenously (IV) followed by cisplatin intraarterially and doxorubicin IV. After surgery, patients classified as good responders (> 90% tumor necrosis) received three more cycles of these drugs, whereas poor responders (< 90% tumor necrosis) had more chemotherapy, which included ifosfamide and etoposide in addition to the other three drugs. Results. Limb salvage was performed in 83% of cases. At an average follow‐up of 54 months (36–76), 109 patients (66%) were continuously disease‐free, 2 died from doxorubicin cardiotoxicity, and 52 experienced metastases and 3 had local recurrence. In two of these three patients, metastases followed local recurrence. The 5‐year actuarial continuously disease‐free survival rate was 63%, with no differences between good and poor responders. Excluding 20 patients who had major protocol violations, the projected continuous disease‐free survival rate was 71%. Conclusions. With an aggressive neoadjuvant chemotherapy, it is possible to cure more than 60% of nonmetastatic osteosarcoma of the extremities, avoiding amputation in most cases. Ifosfamide and etoposide seem to be effective in patients who did not respond to preoperative chemotherapy.

The feasibility of neoadjuvant high‐dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with nonmetastatic high grade localized osteosarcoma

“…29 In the functional analysis of LSS, Bacci et al demonstrated intermediate and good functional results in greater than 70% of patients. 26 We observed good to excellent functionality in 77% of the patients in the current study. We encountered a local recurrence in only 1 patient (4.5%) whereas it has been reported to be approximately 6 -11% in other studies.…”

“…The length of treatment has been reported to be between 21-42 weeks based on data from the various literature. 21,26,27 The overall duration of treatment in the current study was 25 weeks on average, a duration that appears to be shorter than that of the other studies. 1,2,21,26,27,33 LSS has become the standard therapy in patients with nonmetastatic osteosarcoma.…”

“…22,25 The period between the beginning of the induction chemotherapy and surgery and the length of chemotherapy administration before surgery still are reported to vary in different studies. 2,21,26,33 Surgery reportedly has been performed at approximately 9 -11 weeks of induction chemotherapy in other studies. 26,27 However, patients in the current study underwent LSS at approximately the 12th week of induction chemotherapy, similar to most previous studies.…”

“…2,21,26,33 Surgery reportedly has been performed at approximately 9 -11 weeks of induction chemotherapy in other studies. 26,27 However, patients in the current study underwent LSS at approximately the 12th week of induction chemotherapy, similar to most previous studies. The length of treatment has been reported to be between 21-42 weeks based on data from the various literature.…”

Existe diferença no prognóstico de pacientes com osteossarcoma primário com uma pobre resposta à quimioterapia neoadjuvante entre os graus I e II de huvos?

“…2011;46(4):420-23 occurred through adequate staging of these tumors, improved imaging methods and, especially, polychemotherapy. Today, the five-year disease-free survival rate has reached 60-70%, using the most recent chemotherapy protocols (8)(9)(10)(11)(12) . Poor histological response to preoperative chemotherapy, as assessed by the degree of necrosis in the surgical specimen, is also considered to be one of the most important unfavorable prognostic factors relating to the survival of osteosarcoma patients (6,7,8,(13)(14)(15)(16)(17)(18)(19)(20)(21) .…”