Results of the second largest trial ever reported in osteosarcoma, the BO06 trial, have now been published. This trial was run for the European Osteosarcoma Intergroup from the MRC Clinical Trials Unit, London and the EORTC Data Centre, Brussels. 497 patients were enrolled between May 1993 and September 2002.
Osteosarcoma is an uncommon malignancy in bone, most often reported in older children and young adults. The main treatment is surgery with chemotherapy before and after. Some studies in cancers such as non-Hodgkin lymphoma and breast cancer have suggested that increasing the intensity of a chemotherapy regimen - that is, decreasing the number of days between chemotherapy treatments - may improve survival. This trial tested whether survival could be improved by intensifying the conventional two-drug chemotherapy regimen of cisplatin and doxorubicin.
Previously untreated patients with non-metastatic osteosarcoma were randomly assigned Regimen-C (conventional treatment with six 3-week cycles) or Regimen-DI (intensified treatment with identical total doses of cisplatin and doxorubicin, planned as six 2-week cycles supported by granulocyte colony stimulating factor, G-CSF). Surgery was scheduled for week 6 in both arms.
The dose-intense regimen resulted in more patients having tumors with a good response to preoperative chemotherapy (36% of Regimen-C patients compared to 50% of Regimen-DI patients (P=0.003)); a good response (in terms of histology on central review) is prognostic for better outcome. However, there was no evidence of an improvement in overall survival (hazard ratio [HR]=0.94, 95% confidence interval [CI] 0.71 to 1.24; P=0.64), nor was there evidence of an improvement in progression-free survival (HR=0.98, 95% CI 0.77 to 1.24; P=0.83).
"[The good histologic response to preoperative chemotherapy in the dose-intense regimen] did not translate into a demonstratable patient benefit in overall survival or progression-free survival over [the conventional regimen]," the authors write. "This emphasis placed on histologic response as the key treatment-related predictive factor is thereby challenged."
Investigators in this trial are now participating in the EURAMOS 1 trial to see how treatment for these patients might be improved. Visit the EURAMOS website for further information.
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