Author(s): Souhami RL, Craft AW, Van der Eijken JW, Nooij M, Spooner D, , Souhami RL, Craft AW, Van der Eijken JW, Nooij M, Spooner D,
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Abstract BACKGROUND: A previous trial by the European Osteosarcoma Intergroup (EOI) suggested that a short intensive chemotherapy regimen with doxorubicin and cisplatin might produce survival of operable, non-metastatic osteosarcoma similar to that obtained with complex and longer-duration drug regimens based on the widely used T10 multi-drug protocol. We undertook a randomised multicentre trial to compare these two approaches. METHODS: 407 patients with operable, non-metastatic osteosarcoma were randomly assigned the two-drug regimen (six cycles [18 weeks] of doxorubicin 25 mg/m2 on days 1-3 and cisplatin 100 mg/m2 on day 1) or a multi-drug regimen (preoperatively vincristine, high-dose methotrexate, and doxorubicin; postoperatively bleomycin, cyclophosphamide, dactinomycin, vincristine, methotrexate, doxorubicin, and cisplatin; this protocol took 44 weeks). Surgery was scheduled for week 9 for the two-drug group and week 7 for the multi-drug group. Analyses of survival and progression-free survival were by intention to treat. FINDINGS: Of 407 randomised patients, 391 were eligible and have been followed up for at least 4 years (median 5-6 years). Toxic effects were qualitatively similar with the two regimens. However, 188 (94\%) of 199 patients completed the six cycles of two-drug treatment, whereas only 97 (51\%) of 192 completed 18 or more of the 20 cycles of the multi-drug regimen. The proportion showing a good histopathological response (> 90\% tumour necrosis) to preoperative chemotherapy was about 29\% with both regimens and was strongly predictive of survival. Overall survival was 65\% at 3 years and 55\% at 5 years in both groups (hazard ratio 0.94 [95\% CI 0.69-1.27]). Progression-free survival at 5 years was 44\% in both groups (hazard ratio 1.01 [0.77-1.33]). INTERPRETATION: We found no difference in survival between the two-drug and multi-drug regimens in operable, non-metastatic osteosarcoma. The two-drug regimen is shorter in duration and better tolerated, and is therefore the preferred treatment. However, 5-year survival is still unsatisfactory and new approaches to treatment, such as dose intensification, are needed to improve results.
This article was published in Lancet
and referenced in Journal of Cancer Science & Therapy