Cyclophosphamide dose intensification during induction therapy for intermediate-risk pediatric rhabdomyosarcoma is feasible but does not improve outcome: a report from the soft tissue sarcoma committee of the children's oncology group.

Purpose: More than half of pediatric rhabdomyosarcoma cases have intermediate-risk features and suboptimal outcome (3-year failure-free survival estimates, 55 to 76%). Dose intensification of known active agents may improve outcome.

Experimental Design: This pilot study evaluated the feasibility of dose intensification of cyclophosphamide in previously untreated patients ages < 21 years with intermediate-risk rhabdomyosarcoma.

Endostatin-mediated concomitant resistance in neuroblastoma.

Purpose: Concomitant resistance, the phenomenon whereby a primary malignancy inhibits the growth of metastatic lesions, is likely caused by the production of endogenous anti-angiogenic factors. The purpose of this study was to evaluate the influence of the angiogenesis inhibitor, endostatin, expressed by primary sites of neuroblastoma, on synchronous disease.

Methods: Two neuroblastoma models were used.

Autocrine expression of both endostatin and green fluorescent protein provides a synergistic antitumor effect in a murine neuroblastoma model.

Modalities that act through different mechanisms can often provide synergistic antitumor activity for the treatment of refractory tumors when used in combination. Here we report a gene therapy approach in which the genes for the angiogenesis inhibitor, endostatin, and the marker protein and potent immunogen, green fluorescent protein (GFP), were delivered to murine neuroblastoma cells prior to inoculation of the tumor cells into syngeneic immunocompetent mice. Although the effect of either angiogenesis inhibition or immunomodulation alone resulted in only a modest delay in tumor growth, when these approaches were used in combination, prevention of the formation of appreciable tumors was effected in 15 of 24 (63%) mice.