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J Orthop Sci. 2009 Sep;14(5):556-65. doi: 10.1007/s00776-009-1372-5. Epub 2009 Oct 3.

Caffeine-potentiated chemotherapy for metastatic osteosarcoma.

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  • 1Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.



The prognosis for patients with metastatic osteosarcoma is still poor despite the development of effective adjuvant and neoadjuvant chemotherapy regimens. We have developed caffeine-potentiated chemotherapy for treatment of high-grade bone and soft tissue sarcomas based on the ability of caffeine to enhance the cytocidal effects of anticancer drugs. We report results of caffeine-potentiated chemotherapy for patients with osteosarcoma with pulmonary metastases.


We analyzed retrospectively overall survival and some prognostic factors for 41 patients with osteosarcoma/pulmonary metastases who were treated with caffeine-potentiated chemotherapy between 1990 and 2006.


The mean follow-up of all patients was 32.7 months. At the time of the final follow-up, 11 patients were alive and 30 had died of disease. Overall survival rates at 2 and 5 years were 38% and 28%, respectively. We identified the primary tumor site, the histological response to preoperative chemotherapy, the number of pulmonary nodules at initial identification, the timing of pulmonary metastasis identification, and the existence of extrapulmonary metastasis as prognostic factors. Especially, the number of pulmonary nodules at initial identification and the timing of pulmonary metastasis identification were independent, strong prognostic factors. Patients with solitary pulmonary metastasis had good prognoses, and their overall 5-year survival rate was 60%; in contrast, survival was 28% in patients with two to five pulmonary nodules, and no patients with more than six nodules survived 5 years. Patients with pulmonary metastasis identified after completion of treatment had the best prognosis, whereas patients with pulmonary metastases identified during treatment had the worst prognosis.


Caffeine-potentiated chemotherapy prolonged survival of patients who had osteosarcoma with pulmonary metastasis. Especially, patients with pulmonary metastasis identified after completion of treatment or with a solitary pulmonary nodule had good prognoses.

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