CAFFEINE-ASSISTED CHEMOTHERAPY AND MINIMIZED TUMOR-EXCISION FOR NONMETASTATIC OSTEOSARCOMA

Osteosarcoma is usually treated with intensive preoperative and postop erative chemotherapy and wide tumor resection, resulting in a 60% to 7 0% 5-year survival rate. Caffeine has a DNA-repair inhibiting effect W e therefore investigated the impact of caffeine given in conjunction w ith chemotherapy and limb-sparing surgery on survival and local tumor control in patients with nonmetastatic, high-grade osteosarcoma. Twent y-two patients were given 3 to 5 preoperative courses of intra-arteria l cisplatin (120 mg/m(2), 1 to 2 hours) and caffeine (1.5 g/m(2)/day x 3 days) with or without doxorubicin (30 mg/m(2)/day x 2 days). Follow ing this treatment, limb-sparing surgery was performed by means of int entional marginal excision aiming at preservation of important structu res such as major neurovascular bundles, tendons, ligaments and the ep iphysis. Three courses of cisplatin and doxorubicin combined with caff eine, and high-dose methotrexate with vincristine and citrovorum facto r rescue were given intravenously as postoperative chemotherapy for 21 patients and three courses of high-dose methotrexate and combination of ifosfamide, etoposide and methotrexate for 1 patient. Following the preoperative chemotherapy, there were no viable tumor cells in 19 pat ients, only scattered foci of viable cells in 2 patients, and some are as of viable tumor cells in 1. The 22 patients with a good chemotherap eutic response on radiographs underwent minimized marginal excision. F unctional evaluation of the affected limbs was excellent for 17 patien ts, good for 3, fair for 1, and poor for 1. No local tumor recurrence was seen in this series. Eighteen patients remain disease-free with a mean follow-up of 61 months. Two patients died of metastatic disease, 1 died of chemotherapy-related complications, and I died of unknown ca uses The overall 5-year cumulative survival rate was 90%, and the 5-ye ar event-free survival rate was 75%. Chemotherapeutic caffeine enhance d tumor necrosis and improved the success rare of limb-sparing surgery using marginal procedure without any adverse impact on survival The r esults of our limited clinical trial appear to justify further prospec tive, multicenter randomized trials of the benefits of caffeine combin ed with chemotherapy for nonmetastatic osteosarcoma and other malignan t neoplasms.