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Eur J Cancer. 2018 Jan;88:57-66. doi: 10.1016/j.ejca.2017.09.036. Epub 2017 Nov 28.

Results of methotrexate-etoposide-ifosfamide based regimen (M-EI) in osteosarcoma patients included in the French OS2006/sarcome-09 study.

Author information

1
Department of Oncology for Child and Adolescent, Gustave Roussy, Villejuif, France. Electronic address: nathalie.gaspar@gustaveroussy.fr.
2
Biostatistics Department, Institut Gustave Roussy, Villejuif, France.
3
Department of Paediatric Oncology, Institut Curie, Paris, France.
4
Medical Oncology Department, Institut de Cancérologie de l'Ouest, Saint Herblain, France.
5
Department of Pathology, CHU La Timone, Marseille, France.
6
Imaging Department, Institut Curie, Paris, France; Paris-Sciences-et-Lettres Research University, Paris, France.
7
Paediatric Oncology Department, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
8
Pediatric Oncology Department, Hôpital Mère-enfant, Nantes, France.
9
UNICANCER, Paris, France.
10
Paediatric Oncology Department, CHU Hautepierre, Strasbourg, France.
11
Paediatric Oncology Department, CHU La Timone, Marseille, France.
12
Department of Medical Oncology, Institut Bergonie, Bordeaux, France.
13
Paediatric Oncology Unit, Centre Oscar Lambret, Lille, France.
14
Oncopediatric Department, Centre Léon Bérard, Lyon, France.
15
Department of Orthopaedic Surgery, Hôpital Necker, Enfants Malades, Paris, France.
16
Inserm U957-EA 3822, Faculté de Médecine, 1 rue Gaston Veil, Nantes, France.
17
Department of Paediatric Oncology, Hôpital Arnaud de Villeneuve, Montpellier, France.
18
Department of Paediatric Hematology and Oncology, Hôpital d'enfants, Nancy, France.
19
Paediatric Oncology Department, Hôpital Trousseau, Paris, France.
20
Paediatric Oncology Department, CHU de bordeaux, Bordeaux, France.
21
Centre Oscar Lambret, Lille, France; CESP, INSERM, Facult de médecine - Paris-Sud, University Paris-Saclay, F-94805 Villejuif, France.
22
Department of Medical Oncology, Institut Curie, Paris, France.
23
Department of Oncology for Child and Adolescent, Gustave Roussy, Villejuif, France.

Abstract

BACKGROUND:

In most countries, reference chemotherapy for osteosarcoma is MAP regimen (M = high-dose methotrexate, AP = doxorubicin-cisplatinum). In France, the standard preoperative chemotherapy for children/adolescents combines M and etoposide-ifosfamide (EI), based on the OS94-trial. We report the safety and efficacy results of patients ≤25 years treated with preoperative M-EI regimen enroled in the French OS2006-study, between 2007 and 2014.

METHODS:

Treatment comprised preoperative chemotherapy with the 7 M-courses and 2 EI-courses, then surgery and postoperative chemotherapy assigned by risk's groups: standard-risk (good histological response without metastases) received 12 M-courses, 3 EI-courses; high-risk (poor histologic response, initial metastases or unresectable primary) received 5 M-courses alternated with 5 AP-courses. 253 patients were randomised to receive (n = 128) or not (n = 125) zoledronate.

RESULTS:

409/522 patients enroled in the OS2006 study who received preoperative M-EI were analysed. Median age was 14.3 years (4.7-24.5), with 55 patients aged 18-25 years. Primary tumour location was limb in 383 patients (94%) and 85 (21%) presented metastases. Median chemotherapy duration was 37.4 weeks. 381 (96%) patients underwent surgery, 258 patients (65%) had a good histologic response. 187/324 patients (58%) with localised disease did not receive doxorubicin nor cisplatinum. Toxicity was evaluated in the randomised study: most patients experienced ≥1 severe toxicity (grade IV haematological or grade III/IV extra-haematological). Median follow-up was 4.8 years, and 168 patients had events. Five-year event-free survival was 56% (95% CI, 51-62%) and overall survival 71% (66-76%).

CONCLUSION:

M-EI regimen/strategy was feasible for patient aged ≤25 years with survival rates are comparable to those obtained with MAP regimen.

KEYWORDS:

Etoposide; Ifosfamide; Methotrexate; Osteosarcoma

PMID:
29190507
DOI:
10.1016/j.ejca.2017.09.036
[Indexed for MEDLINE]

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