Rapid VAC high dose melphalan regimen, a novel chemotherapy approach in childhood soft tissue sarcomas

Abstract

Summary Forty-three children with malignant soft tissue sarcomas (IRS Groups II-IV) were treated with a rapid dose delivery chemotherapy protocol comprising six courses of vincristine, adriamycin and cyclophosphamide, given in most cases within 8 weeks (Rapid VAC). This was followed in 36 patients by high dose melphalan with autologous bone marrow rescue. Twenty-six patients also received irradiation to the site of primary tumour.The Rapid VAC regimen was well tolerated and largely administered as an out-patient. This treatment strategy utilises the philosophy of rapid drug delivery with high dose consolidation and enables all chemotherapy to be finished within a 4 month period. In general, a conservative approach was applied to both radiation and surgery to minimise late sequelae related to these treatment modalities. Although the small number of high risk patients in this study limits conclusions regarding efficacy in these subgroups the overall results with this regimen appear to be comparable to that with other approaches.

Detection of the PAX3-FKHR fusion gene in paediatric rhabdomyosarcoma: a reproducible predictor of outcome?

“…45 (49%) were treated with the SIOP (International Society of Paediatric Oncology) MMT89 (malignant mesenchymal tumour) protocol and 22 (24%) with the closely related MMT95 protocol, representing 19% of all UK patients entered in these 2 trials. 5 patients were treated before 1989 in the Royal Marsden Hospital using the Rapid VAC protocol (Pinkerton et al, 1991) and 19 others (20%) were treated since 1989 in UK paediatric cancer centres using other multimodality and multiagent chemotherapy protocols of similar intensity to the MMT regimens. All patients were treated with a combination of drugs including vincristine, ifosfamide (or cyclophosphamide), and actinomycin D. Higher stage tumours and some alveolar tumours additionally received epirubicin, etoposide and carboplatin.…”

Intensive chemotherapy for children and young adults with metastatic primitive neuroectodermal tumors of the soft tissue

“…Benefit has been shown in the treatment of metastatic neuroblastoma 16 and, recently, promising results have also been reported in adult patients with advanced soft tissue sarcoma. 17 In children, previous experience failed to show a better outcome for metastatic rhabdomyosarcoma 10,18 or bony Ewing's sarcoma. 19 In the MMT4 studies there was evidence that high-dose consolidation therapy with melphalan may have delayed relapse but it did not ultimately improve the survival of patients with metastatic rhabdomyosarcoma.…”

Autologous stem cell transplantation for high-risk pediatric solid tumors

“…Previous reports have documented a 3-20% incidence of transplant-related mortality following autotransplantation for pediatric solid tumors. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] The first regimen that we evaluated, protocol MT 8911, consisting of etoposide, thiotepa and cyclophosphamide was associated with one patient experiencing peri-transplant mortality. The second regimen that we evaluated, MT 9408, consisted exclusively of alkylating drugs (busulfan, melphalan and thiotepa) and was associated with two toxic deaths, both from complications of hepatic veno-occlusive disease.…”

“…[1][2][3] ASCT is under evaluation as consolidation therapy for patients with metastatic disease and for those who have relapsed after intensive therapies. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Durable responses have been reported for neuroblastoma, 10,13,14,16 Ewing's sarcoma, 5,9,[15][16][17] rhabdomyosarcoma, 8,15,17 Wilms tumor 15,18 and brain tumors. [19][20][21][22][23][24][25][26] We present our experience with two consecutive studies evaluating the role of myeloablative chemotherapy followed by ASCT for young patients with aggressive solid tumors.…”