Intensive Induction Chemotherapy without Methotrexate in Adult Patients with Localized Osteosarcoma: Results of the Institut Gustave-Roussy Phase II Trial

Abstract

Purpose: To improve outcomes in localized osteosarcoma and to reduce the duration of preoperative chemotherapy, we conducted a phase ii trial assessing the efficacy of an intensive protracted regimen without methotrexate (API-AI regimen) in adolescent and adult patients with newly diagnosed disease. Patients and Methods: Induction chemotherapy consisted of 2 cycles (4 courses) of doxorubicin 60 mg/m2 (days 1 and 15), cisplatin 100 mg/m2 (day 1), and ifosfamide 5 g/m2 (days 2 and 15). The primary endpoint was good histologic response [GHR (≤5% identifiable tumour cells)]. Results: From March 1993 to March 2000, 32 patients [median age: 21 years (range: 15–49 years)] were administered 126 induction courses. The median time between chemotherapy courses was 15 days (range: 12–32 days). All but 3 patients underwent conservative surgery. Toxicity was mainly hematologic, with febrile neutropenia occurring in 35% of patients and grades 3–4 thrombocytopenia in 35%. The GHR rate was 47%. The median follow-up was 64 months (range: 30–115 months). The 5-year event-free and overall survivals were 65% [95% confidence interval (CI): 48–79%] and 69% (95% CI: 50–83%) respectively. Two secondary hematologic malignancies occurred: 1 acute myelocytic leukemia (M5) in a poor responder with concomitant relapse, and 1 myelodysplastic syndrome in a patient achieving GHR. Conclusions: Despite hematologic toxicity, the results observed with the API-AI regimen compare favourably with those observed during previous induction chemotherapy containing methotrexate in adult patients and the pediatric population treated at our institution. These promising results have to be validated by an ongoing national multicentre trial coordinated by the French Sarcoma Group.

Clinical Analysis of Osteosarcoma Patients Treated with High-Dose Methotrexate-Free Neoadjuvant Chemotherapy

“…In two studies using different protocols, hdmtxfree dia regimens resulted in 5-year os and efs rates of 69% and 74% and of 65% and 68% respectively 17,21 , which are comparable to rates achieved with hdmtxcontaining regimens. In a recent phase ii clinical trial (OS99), a hdmtx-free regimen comprising carboplatin, ifosfamide, and doxorubicin resulted in 5-year os and efs rates of 78.9% and 61% respectively 23 .…”

“…After follow-up for an average of 66 months, the 5-year os was 61.5% and the disease-free survival was 54.8% in our cohort. Taken together, the data indicate that hdmtx-free chemotherapy regimens produce survival outcomes comparable to those with hdmtx-containing regimens in osteosarcoma patients 3,15,16,20,21 . The hdmtx-free regimens are well tolerated, do not require pharmacokinetic monitoring, and avoid the toxicities and side effects associated with hdmtx and cisplatin.…”

Abdominal Desmoplastic Small Round Cell Tumor: Multimodal Treatment Combining Chemotherapy, Surgery, and Radiotherapy is the Best Option

“…mesna, day 1 = day 21), n = 10. 20 Cisplatin-5-fluorouracil and VACA were provided to 2 and 1 patient, respectively. 21 Patients received a median number of 4 cycles (range 4-7 cycles).…”

Alcohol-Inactivated Autograft Replantation with Joint Preservation in the Management of Osteosarcoma of the Distal Femur: A Preliminary Study

“…The diagnoses were consistent in all patients before and after surgery. All patients received preoperative cisplatin, ifosfamide and adriamycin (DIA) chemotherapy [11,12,13]. The tumor boundary was identified by magnetic resonance imaging (MRI) before and after chemotherapy.…”

“…Sutures were removed 12-14 days after surgery and postoperative chemotherapy was initiated. Patients received 6 courses of postoperative DIA chemotherapy (adriamycin, 30 mg/m 2 × 3 days; ifosfamide, 2 g/m 2 × 5 days; and cisplatin, 120 mg/m 2 × 1 day) [11,12,13]. The regimen was chosen according to the postoperative histological response to chemotherapy represented as tumor cell necrosis rate (TCNR), which is semiquantitatively classified into 4 grades [16].…”