osteosarcoma1999-a study of intensive chemotherapy for osteosarcoma

Conditions: Osteosarcoma

Summary: this trial (os99) evaluates the use of ifosfamide, carboplatin, and doxorubicin in an up-front window before surgery for localized and resectable osteosarcoma. high-dose methotrexate, which may interfere with the dose-intensive delivery of other agents, is eliminated from the treatment of localized disease. the primary objective is to compare the response rate of pre-surgical chemotherapy comprised of ifosfamide, doxorubicin, and carboplatin to that obtained with ifosfamide and carboplatin in the st. jude os-91 trial for patients with non-metastatic resectable osteosarcoma. we hypothesize that the histologic response rate will be improved by the addition of one course of pre-operative chemotherapy on this trial compared to the previous os-91 trial.

this study has multiple research objectives: * to compare the response rate of pre-surgical chemotherapy comprised of ifosfamide, doxorubicin, and carboplatin to that obtained with ifosfamide and carboplatin in the st. jude os-91 trial for patients with non-metastatic resectable osteosarcoma * to continue the evaluation of dynamic contrast-enhanced magnetic resonance imaging (demri) in predicting tumor response and accurately assessing the degree of response (continued from os-91). * to determine the feasibility of delivering outpatient-based chemotherapy for osteosarcoma using ifosfamide-doxorubicin-carboplatin. * to determine whether resection of the primary site may be satisfactorily performed with a 3 cm margin of normal bone (rather than 5 cm). * to study biologic and biochemical characteristics of the tumor cells that may be of prognostic significance * to study the patients' and parents' perspectives of the patients' quality of life during and after treatment. description of treatment plan: this study employs the following treatment strategy: neoadjuvant chemotherapy followed by definitive surgery for local control and adjuvant chemotherapy after tumor resection. pre-operative chemotherapy phase (weeks 0-12): three courses of ifosfamide/carboplatin given every 3 weeks followed by one 3-week course of doxorubicin.disease evaluation is performed after 3 courses and after 4 courses of chemotherapy. weeks 0, 3, and 6 - ifosfamide-carboplatin ifosfamide: 2.65 gm/m2 iv daily over 15-30 minutes x 3 (days 1, 2, 3) with mesna. carboplatin: dose based on gfr and targeted to an auc of 8 mg/ml/min, given iv over 1 hour (day 1 only) week 9- evaluation, followed by doxorubicin doxorubicin: 25 mg/m2 iv over 1 hour, daily x 3 week 12 evaluation followed by definitive surgery local control by amputation or limb-salvage procedure post-operative chemotherapy (weeks 14-35) ifosfamide, carboplatin, and doxorubicin in two-agent pairs for approximately 35 weeks. week 14 - ifosfamide-doxorubicin ifosfamide: 2.65 gm/m2 iv daily over 15-30 minutes x 3 (days 1, 2, 3) with mesna, doxorubicin: 25 mg/m2 iv over 1 hour, daily x 2 (days 1 and 2) week 17 - ifosfamide-carboplatin ifosfamide: 2.65 gm/m2 iv daily over 15-30 minutes x 3 (days 1, 2, 3) with mesna, carboplatin: targeted to an auc of 8 mg/ml/min given iv over 1 hour (day 1 only) week 20 - carboplatin-doxorubicin carboplatin: targeted to an auc of 8 mg/ml/min given iv over 1 hour (day 1 only), doxorubicin: 25 mg/m2 iv over 1 hour, daily x 2 (days 1 and 2) week 23 - evaluation, followed by ifosfamide: doxorubicin. ifosfamide: 2.65 gm/m2 iv daily over 15-30 minutes x 3 (days 1, 2, 3) with mesna, doxorubicin: 25 mg/m2 iv over 1 hour, daily x 2 (days 1 and 2) week 26 - ifosfamide-carboplatin ifosfamide: 2.65 gm/m2 iv daily over 15-30 minutes x 3 (days 1, 2, 3) with mesna, carboplatin: targeted to an auc of 8 mg/ml/min given iv over 1 hour (day 1 only) week 29 - carboplatin-doxorubicin carboplatin: targeted to an auc of 8 mg/ml/min given iv over 1 hour (day 1 only), doxorubicin: 25 mg/m2 iv over 1 hour, daily x 2 (days 1 and 2) week 32 - evaluation, followed by ifosfamide-doxorubicin. ifosfamide: 2.65 gm/m2 iv daily over 15-30 minutes x 3 (days 1, 2, 3) with mesna, doxorubicin: 25 mg/m2 iv over 1 hour, daily x 2 (days 1 and 2) week 35 - carboplatin-doxorubicin carboplatin: targeted to an auc of 8 mg/ml/min given iv over 1 hour (day 1 only), doxorubicin: 25 mg/m2 iv over 1 hour, daily x 2 (days 1 and 2)

Eligibility criteria:
inclusion criteria: * all subjects with histologically proven high-grade osteosarcoma,chondrosarcoma, mfh, fibrosarcoma or chondrosarcoma of bone, whose tumors are potentially resectable (either by limb sparing, en bloc resection, or amputation) and have no evidence of metastasis. * adequate liver, renal and cardiac function. * age: younger than 25 years old exclusion criteria: * prior chemotherapy

Keywords: osteosarcoma treatment, carboplatin