Long term survival in adult osteosarcoma patients treated with a two-drug regimen: Final results of the OSAD93 phase II study of the FSG-GETO

• Published in: European journal of cancer (1990) Vol. 208; p. 114228
• Main Authors: Blay, Jean-Yves, Penel, Nicolas, Toulmonde, Maud, Valentin, Thibaud, Chaigneau, Loic, Rios, Maria, Saada-Bouzid, Esma, Firmin, Nelly, Bertucci, Francois, Marec-Berard, Perrine, Ray-Coquard, Isabelle, Lervat, Cyril, Rolland, Frederic, Thyss, Antoine, Conroy, Thierry, Brahmi, Mehdi, Dufresne, Armelle, Merrouche, Yacine, Brunat-Mentigny, Maud, Biron, Pierre, Bompas, Emmanuelle, Perol, David
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2024; Elsevier
• Subjects: Anthracuyclins; Cancer; CDDP; High grade; Ifosfamide; Life Sciences; Osteogenic sarcoma; Rare cancers; Reference centers; Survival; Reference centers; Rare cancers; CDDP; Ifosfamide; Osteogenic sarcoma; Anthracuyclins; Survival; High grade
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2024.114228

We report a phase II trial (OSAD93) testing CDDP with ifosfamide (IFO), without doxorubicin in neoadjuvant phase, in adult osteosarcoma with a 25 years follow-up. This is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m2 and CDDP 100 mg/m2 on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie ≤ 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives. From Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16–63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3–4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months. Though the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma. OSAD93 used a 2 drugs neoadjuvant chemotherapy regimen in adult osteosarcoma.The primary endpoint (good histological response in >30 % of patients) was not metThe long term (>25y) OS & DFS are high in this adult osteosarcoma series.Limited long-term toxicity and no cardiac toxicity was observed in cured patients.This protocol provides excellent long-term results, deserving further investigations.