Intensive induction chemotherapy without methotrexate in adult patients with localized osteosarcoma: results of the Institut Gustave-Roussy phase II trial

H. Assi, G. Missenard, P. Terrier, C. Le Pechoux, S. Bonvalot, D. Vanel, J.B. Meric, T. Tursz, A. LeCesne

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 (less than or equal to 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.


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DOI: http://dx.doi.org/10.3747/co.v17i6.578






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