Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial.

Background: We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma.

Methods: EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation.

Intensified Chemotherapy With Dexrazoxane Cardioprotection in Newly Diagnosed Nonmetastatic Osteosarcoma: A Report From the Children's Oncology Group.

Background: Although chemotherapy has improved outcome of osteosarcoma, 30-40% of patients succumb to this disease. Survivors experience substantial morbidity and mortality from anthracycline-induced cardiotoxicity. We hypothesized that the cardioprotectant dexrazoxane would (i) support escalation of the cumulative doxorubicin dose (600 mg/m(2)) and (ii) not interfere with the cytotoxicity of chemotherapy measured by necrosis grading in comparison to historical control data.

Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial.

Purpose: EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy.

Patients And Methods: At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression.

EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment.

Background: Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response.

Patients And Methods: Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery.

Analysis of serum insulin growth factor-1 concentrations in localized osteosarcoma: a children's oncology group study.

To investigate the role of insulin-like growth factor-1 (IGF-1), in localized osteosarcoma, serum levels of IGF-1, IGFBP-2, and IGFBP-3 were measured in 224 similarly treated, newly diagnosed patients. We demonstrated that younger patients had lower concentrations of IGF-1 and IGFBP-3 compared to older (P < 0.001) along with lower IGFBP-3:IGF-1 and IGFBP-2:IGF-1 ratios (P < 0.

Phase II trial of trastuzumab in combination with cytotoxic chemotherapy for treatment of metastatic osteosarcoma with human epidermal growth factor receptor 2 overexpression: a report from the children's oncology group.

Purpose: Despite efforts to intensify chemotherapy, survival for patients with metastatic osteosarcoma remains poor. Overexpression of human epidermal growth factor receptor 2 (HER2) in osteosarcoma has been shown to predict poor therapeutic response and decreased survival. This study tests the safety and feasibility of delivering biologically targeted therapy by combining trastuzumab with standard chemotherapy in patients with metastatic osteosarcoma and HER2 overexpression.

Inhaled granulocyte-macrophage colony stimulating factor for first pulmonary recurrence of osteosarcoma: effects on disease-free survival and immunomodulation. a report from the Children's Oncology Group.

Purpose: Osteosarcoma most commonly recurs in the lung. Based on preliminary data on the antitumor effects of granulocyte-macrophage colony stimulating factor (GM-CSF) in animal models, and promising phase I trials, we embarked on a feasibility study of inhaled GM-CSF in patients with first isolated pulmonary recurrence of osteosarcoma.

Experimental Design: Forty-three eligible patients received inhaled GM-CSF at doses from 250 to 1,750 microg twice daily on alternate weeks.

Dose-intensified compared with standard chemotherapy for nonmetastatic Ewing sarcoma family of tumors: a Children's Oncology Group Study.

Purpose: The Ewing sarcoma family of tumors (ESFT) is a group of malignant tumors of soft tissue and bone sharing a chromosomal translocation affecting the EWS locus. The Intergroup INT-0091 demonstrated the superiority of a regimen of vincristine, cyclophosphamide, doxorubicin (VDC), and dactinomycin alternating with ifosfamide and etoposide (IE) over VDC for patients with nonmetastatic ESFT of bone. The goal of this study was to determine whether a dose-intensified regimen of VDC alternating with IE would further improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.

Ototoxicity in children treated for osteosarcoma.

Background: Cisplatin is an effective agent against osteosarcoma. Ototoxicity from osteosarcoma treatment protocols has not been well defined. The aim of this study was to determine the incidence and risk factors for hearing loss in children treated for osteosarcoma.

Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival--a report from the Children's Oncology Group.

Purpose: To compare three-drug chemotherapy with cisplatin, doxorubicin, and methotrexate with four-drug chemotherapy with cisplatin, doxorubicin, methotrexate, and ifosfamide for the treatment of osteosarcoma. To determine whether the addition of muramyl tripeptide (MTP) to chemotherapy enhances event-free survival (EFS) and overall survival in newly diagnosed patients with osteosarcoma.

Patients And Methods: Six hundred sixty-two patients with osteosarcoma without clinically detectable metastatic disease and whose disease was considered resectable received one of four prospectively randomized treatments.

Multiple drug resistance in osteogenic sarcoma: INT0133 from the Children's Oncology Group.

Purpose: Multiple drug resistance due to P-glycoprotein (P-gp) expression has been reported to be a cause of disease recurrence in osteosarcoma. Tumor specimens derived from children and young adults with osteosarcoma enrolled onto a national Intergroup trial (INT0133) were analyzed prospectively to determine the role of multiple drug resistance in osteosarcoma.

Patients And Methods: From October 15, 1992, to November 25, 1997, 685 patients with localized, high-grade osteosarcoma were enrolled onto INT0133.

Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457--a report from the Children's Oncology Group.

Purpose: Prognosis is poor for Ewing sarcoma patients with metastasis at diagnosis. We intensified a five-drug therapy (ifosfamide, etoposide alternated with vincristine, doxorubicin, and cyclophosphamide) using filgrastim but not stem-cell support. We studied topotecan alone and combined with cyclophosphamide in therapeutic windows before the five-drug therapy.

Osteosarcoma: a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate.

Purpose: To determine whether the addition of ifosfamide and/or muramyl tripeptide (MTP) encapsulated in liposomes to cisplatin, doxorubicin, and high-dose methotrexate (HDMTX) could improve the probability for event-free survival (EFS) in newly diagnosed patients with osteosarcoma (OS).

Patients And Methods: Six hundred seventy-seven patients with OS without clinically detectable metastatic disease were treated with one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and HDMTX and underwent definitive surgical resection of the primary tumor.

Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent osteosarcoma.

Background: Recurrent osteosarcoma is a drug-resistant disease with a dismal prognosis. The objective of this Phase II study was to evaluate the activity of ecteinascidin 743 (ET-743) as a salvage therapy in these patients.

Methods: Patients with recurrent osteosarcoma who had received standard chemotherapeutic agents were eligible.

Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651.

Purpose: Successful therapeutic interventions to prevent disease progression in patients with nonmetastatic osteosarcoma have included surgery with adjuvant chemotherapy. Presurgical chemotherapy has been advocated for these patients because of putative improvement in event-free survival (EFS). The advantages of presurgical chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups.

Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial.

Purpose: The objectives of this trial were to estimate the response rate, progression-free survival, and overall survival of patients who received therapy with etoposide and high-dose ifosfamide, and to define the toxicity of this combination when provided with standard chemotherapy in patients with newly diagnosed metastatic osteosarcoma.

Patients And Methods: Eligible patients received infusions of 100 mg/m(2) per day of etoposide and 3.5 g/m(2) per day of ifosfamide for 5 days.

Presurgical window of carboplatin and surgery and multidrug chemotherapy for the treatment of newly diagnosed metastatic or unresectable osteosarcoma: Pediatric Oncology Group Trial.

Purpose: Relapse remains a significant problem in patients with metastatic osteosarcoma. The response to carboplatin of patients with newly diagnosed metastatic or unresectable osteosarcoma was assessed in an upfront phase II window, which was followed-up by surgery and intensive multiagent chemotherapy.

Patients And Methods: Thirty-seven patients, ages 3 to 23 years with histologically confirmed diagnoses of osteosarcoma, were treated between January 1992 and November 1994 with carboplatin 1,000 mg/m2 per dose administered as a 48-hour continuous infusion.

Current treatment of osteosarcoma.

A comprehensive multidisciplinary approach has transformed osteosarcoma from a disease with a modest long-term survival to one in which at least two-thirds of patients will be cured. Surgery remains the vital modality for treating the primary tumor, whereas adjuvant chemotherapy plays an essential role in the control of subclinical metastatic disease. Complete surgical excision of the primary tumor remains an essential element of treatment.

Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study.

Purpose: To estimate the duration of survival (S) of patients with metastatic osteosarcoma (MOS) at diagnosis treated with a multiagent, ifosfamide-containing chemotherapeutic and surgical regimen and to evaluate the toxicity of this regimen.

Patients And Methods: Thirty patients aged younger than 30 years received two courses of ifosfamide followed by surgery on the primary tumor and metastatic sites. Patients then received a postsurgical multiagent chemotherapeutic regimen that consisted of high-dose methotrexate (HDMTX), ifosfamide, doxorubicin, and cisplatin.

Clinical cardiotoxicity following anthracycline treatment for childhood cancer: the Pediatric Oncology Group experience.

Purpose: To determine the incidence of clinical cardiotoxicity from anthracycline chemotherapy in children with cancer and to identify associated risk factors.

Patients And Methods: The study population consisted of 6,493 children with cancer who had received anthracycline chemotherapy on Pediatric Oncology Group (POG) protocols from 1974 to 1990. Cardiotoxicity, defined as congestive heart failure not due to other causes, abnormal measurements of cardiac function that prompted discontinuation of therapy, or sudden death from presumed cardiac causes, was determined by a review of protocol records.

Methotrexate osteopathy in patients with osteosarcoma.

Purpose: To determine the frequency of osteopathy in patients treated with high-dose, short-term, intravenous methotrexate for osteosarcoma and whether this complication varies with patient age and methotrexate dose.

Materials And Methods: Radiographs and available scintigrams of 87 patients with osteosarcoma who received high-dose methotrexate were reviewed retrospectively for severe osteopenia, dense zones of provisional calcification, insufficiency fractures, and involvement of multiple bones. At least three of these radiographic abnormalities were required for the diagnosis of osteopathy.

Long-term pulmonary toxicity of multiagent chemotherapy including bleomycin and cyclophosphamide in osteosarcoma survivors.

Purpose: To assess long-term pulmonary effects of multiagent chemotherapy, we studied serial pulmonary function tests (PFTs) of 35 children with osteosarcoma up to 12 years after diagnosis.

Patients And Methods: We analyzed 84 sets of PFTs from 35 patients diagnosed with osteosarcoma between 1981 and 1991. They received bleomycin, cyclophosphamide, methotrexate, doxorubicin, cisplatin, and actinomycin D over 9-12 months and we performed PFTs from 3 days to 152 months after diagnosis.

Donor immunization with Haemophilus influenzae type b (HIB)-conjugate vaccine in allogeneic bone marrow transplantation.

Bone marrow transplant patients are at increased risk for infections with polysaccharide encapsulated organisms and respond poorly to polysaccharide vaccines. We evaluated the effect of donor immunization with Haemophilus influenzae type b (HIB) polysaccharide-conjugate vaccine on recipient antibody responses following allogeneic bone marrow transplantation. Thirty-two allogeneic transplant patients and their donors were immunized before transplantation with HIB-conjugate, tetanus toxoid and 23-valent pneumococcal vaccines.

Pneumococcal conjugate vaccine primes for antibody responses to polysaccharide pneumococcal vaccine after treatment of Hodgkin's disease.

Thirty-nine previously treated Hodgkin's disease (HD) patients were immunized with 7-valent pneumococcal conjugate vaccine (7-OMPC) followed by one dose of 23-valent polysaccharide pneumococcal vaccine (23-PS). To determine the priming effect of 7-OMPC vaccine, their antibody responses to six serotypes contained in both vaccines were compared to those of 57 HD patients who received 23-PS vaccine only. The geometric mean antibody concentrations after immunization with 23-PS vaccine were significantly higher for five of the six measured serotypes in HD patients primed with 7-OMPC vaccine compared with responses in HD patients who received 23-PS vaccine only.