Open-label, multicentre, randomised, phase II study of the EpSSG and the ITCC evaluating the addition of bevacizumab to chemotherapy in childhood and adolescent patients with metastatic soft tissue sarcoma (the BERNIE study) (original) (raw)
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Journal of Clinical Oncology
PURPOSE The primary aim of this clinical trial was to prioritize bevacizumab or temsirolimus for additional investigation in rhabdomyosarcoma (RMS) when administered in combination with cytotoxic chemotherapy to patients with RMS in first relapse with unfavorable prognosis. PATIENTS AND METHODS Patients were randomly assigned to receive bevacizumab on day 1 or temsirolimus on days 1, 8, and 15 of each 21-day treatment cycle, together with vinorelbine on days 1 and 8, and cyclophosphamide on day 1 for a maximum of 12 cycles. Local tumor control with surgery and/or radiation therapy was permitted after 6 weeks of treatment. The primary end point was event-free survival (EFS). Radiographic response was assessed at 6 weeks. The study had a phase II selection that was design to detect a 15% difference between the two regimens (α = .2; 1-β = 0.8; two sided test). RESULTS Eighty-seven of 100 planned patients were enrolled when the trial was closed after the second interim analysis after 46...
Journal of Clinical Oncology, 2012
Purpose MMT95 was the fourth of a series of International Society of Pediatric Oncology (SIOP) collaborations for children with high-risk nonmetastatic soft tissue sarcoma (STS). The principal objective was to explore survival advantage for an intensified chemotherapy strategy in a randomized trial. Patients and Methods From July 1995 to June 2003, 457 previously untreated patients with incompletely resected embryonal rhabdomyosarcoma (RMS), undifferentiated sarcoma, and soft tissue primitive neuroectodermal tumor at all sites except paratesticular, vagina, and uterus, or with alveolar RMS were randomly assigned to receive either ifosfamide, vincristine, and dactinomycin (IVA) or a six-drug combination (IVA plus carboplatin, epirubicin, and etoposide) both delivered over 27 weeks. Cumulative doses were as follows: ifosfamide 54 g/m2 (both arms), epirubicin 450 mg/m2, etoposide 1,350 mg/m2 (six-drug regimen). Poor responders after three courses of IVA were to be switched to the other...
Journal of Clinical Oncology, 2009
The purpose of this study was to compare the outcome of patients with intermediate-risk rhabdomyosarcoma (RMS) treated with standard VAC (vincristine, dactinomycin, and cyclophosphamide) chemotherapy to that of patients treated with VAC alternating with vincristine, topotecan, and cyclophosphamide (VAC/VTC).
European Journal of Cancer, 1998
The second International Society of Paediatric Oncology (SIOP) study for rhabdomyosarcoma (MMT84) had several goals. The two principal aims were: (1) to improve the survival of children with rhabdomyosarcoma; and (2) to reduce the late eVects from therapy by restricting the indications for surgery and/or radiotherapy after good response to initial chemotherapy. A further aim was to investigate the role of high-dose chemotherapy in young patients with parameningeal primary tumours. 186 previously untreated eligible patients entered the study. Patients with completely resected primary tumour received three courses of IVA (ifosfamide, vincristine and actinomycin D). Patients with incompletely resected tumour received six to 10 courses of IVA according to stage. Patients achieving complete remission with chemotherapy alone did not usually receive radiotherapy or undergo extensive surgery, but patients remaining in partial remission received local therapy with surgery and/or radiotherapy. Only patients over 5 years of age with parameningeal disease and patients over 12 years with tumours at any site were given systematic irradiation. Complete remission was achieved in 91% (170/186) of all patients. With a median follow-up of 8 years, the 5-year overall survival was 68% (3% standard error of the mean (SEM)) and the 5-year event-free survival 53% (4% SEM). These results show an improvement over previous SIOP study (RMS75) in which survival was 52% and event-free survival was 47%. Among the 54 patients who exhibited isolated local relapse, 35% (19/54) survived in further remission longer than 2 years after retreatment, including local therapy (surgery radiotherapy). Analysis of the overall burden of therapy received by all surviving children (including primary treatment and treatment for relapse if required) showed that 24% (28/116) were treated by limited surgery followed by three courses of IVA, 29% (34/116) were treated by chemotherapy alone (after initial biopsy) and 13% (15/116) received chemotherapy plus conservative local treatment (limited surgery or radiotherapy for residual disease). Only 34% (39/116) received intensive local therapy de®ned as radical wide ®eld radiotherapy or radical surgery or both. Compared with the results obtained in the previous SIOP study, treatment in MMT84 was based on response to initial chemotherapy and, despite an overall reduction of the use of local therapy, signi®cantly improved survival for patients with non-metastatic disease. This trial, also for the ®rst time, provides evidence that retreatment after local relapse can achieve long-term second remissions.
Cancer and Oncology Research, 2014
Background. Survival rates of pediatric Rhabdomyosarcoma (RMS) have been tremendously improved during the last decade by the development of risk stratification. This has favored tailoring treatment using multi-therapeutic modalities. Methods. Upfront surgical resection was followed by systemic chemotherapy using Vincristine/Actinomycine-D/Cyclophosphamide (VAC) regimen with subsequent further local control by surgery and or radiotherapy according to risk stratification status. Results. Study included 40 patients; their median age was 3.5 years (range: 8 m to 17 yrs) with M/F: 28/12. The 2 years Overall Survival (OS) and Event Free Survival (EFS) for all study patients was 87% and 45% respectively. By univariate analysis, OS was 100% if CR (complete response) versus 92% if PR (partial response) (p=0.03), and was 94% if no distant metastasis versus 66% if present (p=0.024). On the other hand, EFS was 88% with CR versus 46% in PR patients (p <0.001), and was 80% if upfront surgery was done versus 33% if only simple biopsy taken (p=0.03). Local radiotherapy versus no radiotherapy was highly associated with EFS difference as well (75% versus 0%, respectively; p<0.001). In multivariate analysis, local radiotherapy found to be an independent prognostic factor of EFS (95% CI: 2.5-31). Conclusion. Disease extent as well as treatment response are two important factors influenced survival in our RMS patients. Local control measures including surgical resection as well as radiotherapy are crucial variables that predicted EFS. The poor outcome of patients with metastatic disease necessitates further therapeutic approaches.