BACKGROUND: For more than three decades, standard treatment for rhabdomyosarcoma in Europe has included 6 months of chemotherapy. The European paediatric Soft tissue sarcoma Study Group (EpSSG) aimed to investigate whether prolonging treatment with maintenance chemotherapy would improve survival in patients with high-risk rhabdomyosarcoma. METHODS: RMS 2005 was a multicentre, open-label, randomised, controlled, phase 3 trial done at 102 hospitals in 14 countries. We included patients aged 6 months to 21 years with rhabdomyosarcoma who were considered to be at high risk of relapse: those with non-metastatic incompletely resected embryonal rhabdomyosarcoma occurring at unfavourable sites with unfavourable age (≥10 years) or tumour size (>5 cm), or both; those with any non-metastatic rhabdomyosarcoma with nodal involvement; and those with non-metastatic alveolar rhabdomyosarcoma but without nodal involvement. Patients in remission after standard treatment (nine cycles of ifosfamide, vincristine, dactinomycin with or without doxorubicin, and surgery or radiotherapy, or both) were randomly assigned (1:1) to stop treatment or continue maintenance chemotherapy (six cycles of intravenous vinorelbine 25 mg/m2 on days 1, 8, and 15, and daily oral cyclophosphamide 25 mg/m2, on days 1-28). Randomisation was done by use of a web-based system and was stratified (block size of four) by enrolling country and risk subgroup. Neither investigators nor patients were masked to treatment allocation. The primary outcome was disease-free survival in the intention-to-treat population. Secondary outcomes were overall survival and toxicity. This trial is registered with EudraCT, number 2005-000217-35, and ClinicalTrials.gov, number NCT00339118, and follow-up is ongoing. FINDINGS: Between April 20, 2006, and Dec 21, 2016, 371 patients were enrolled and randomly assigned to the two groups: 186 to stop treatment and 185 to receive maintenance chemotherapy. Median follow-up was 60·3 months (IQR 32·4-89·4). In the intention-to-treat population, 5-year disease-free survival was 77·6% (95% CI 70·6-83·2) with maintenance chemotherapy versus 69·8% (62·2-76·2) without maintenance chemotherapy (hazard ratio [HR] 0·68 [95% CI 0·45-1·02]; p=0·061), and 5-year overall survival was 86·5% (95% CI 80·2-90·9) with maintenance chemotherapy versus 73·7% (65·8-80·1) without (HR 0·52 [95% CI 0·32-0·86]; p=0·0097). Toxicity was manageable in patients who received maintenance chemotherapy: 136 (75%) of 181 patients had grade 3-4 leucopenia, 148 (82%) had grade 3-4 neutropenia, 19 (10%) had anaemia, two (1%) had thrombocytopenia, and 56 (31%) had an infection. One (1%) patient had a grade 4 non-haematological toxicity (neurotoxicity). Two treatment-related serious adverse events occurred: one case of inappropriate antidiuretic hormone secretion and one of a severe steppage gait with limb pain, both of which resolved. INTERPRETATION: Adding maintenance chemotherapy seems to improve survival for patients with high-risk rhabdomyosarcoma. This approach will be the new standard of care for patients with high-risk rhabdomyosarcoma in future EpSSG trials. FUNDING: Fondazione Città della Speranza, Association Léon Berard Enfant Cancéreux, Clinical Research Hospital Program (French Ministry of Health), and Cancer Research UK.
- MeSH
- alveolární rhabdomyosarkom farmakoterapie mortalita patologie MeSH
- časové faktory MeSH
- cyklofosfamid aplikace a dávkování škodlivé účinky MeSH
- dítě MeSH
- embryonální rhabdomyosarkom farmakoterapie mortalita patologie MeSH
- hodnocení rizik MeSH
- indukce remise MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- přežití bez známek nemoci MeSH
- progrese nemoci MeSH
- protokoly protinádorové kombinované chemoterapie aplikace a dávkování škodlivé účinky MeSH
- rizikové faktory MeSH
- udržovací chemoterapie * škodlivé účinky mortalita MeSH
- vinorelbin aplikace a dávkování škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Argentina MeSH
- Brazílie MeSH
- Evropa MeSH
- Izrael MeSH
V práci sa hodnotia 9-ročné skúsenosti s diagnostikou a liečbou embryonálneho rhabdomyosarkómu orbity u detí. Podrobne je hodnotený súbor 5 detí liečený a sledovaný 1 - 9 rokov. Vďaka využitiu komplexnej chirurgickej, radiačnej a chemoterapeutickej liečby prežívajú všetci pacienti, z ktorých má 80 % zachovalé zrakové funkcie. Pre diferenciálnodiagnostické problémy pri variabilnej manifestácii rhabdomyosarkómu, ktorý môže imitovať orbitocellulitídu, chalazeon, epibulbarny lipodermoid alebo papilóm, je kladený vefký dôraz na primárnu rýchlu diagnostiku prostredníctvom NMR a biopsie. V liečbe je vysoko hodnotená kombinácia rádioterapie a chemoterapie, ktorá predstavuje moderný trend a dokáže vyliečiť tumor i bez radiálneho chirurgického výkonu.
The authors evaluated 9 years' experience with the diagnosis and treatment of embryonic rhabdomyosarcoma of the orbit in children. They evaluated in detail a group of 5 children treated and followed up for 1 - 9 years. Due to comprehensive surgical, radiation and chemotherapeutic treatment all patients survive and in 80 % the visual function is preserved. For differential diagnostic problems, with regard to the variable manifestation of rhabdomyosarcoma which may imitate orbitocellulitis, chalaseon, epibulbar lipodermoid or papilloma, the authors emphasize the importance of rapid primary diagnosis by NMR and biopsy. In the treatment they appreciate greatly a combination of radiotherapy and chemotherapy which is a modern trend and can erradicate the tumour without radical surgery.
