Comparison of intra-arterial cis-diamminedichloroplatinum II with high-dose methotrexate and citrovorum factor rescue in the treatment of primary osteosarcoma.

Abstract

A randomized two-arm study was undertaken to determine relative tumoricidal effects of intra-arterial cis-diamminedichloroplatinum II (I/A-CDP) and high-dose methotrexate with citrovorum factor rescue (MTX-CF) in the treatment of the primary tumor in patients with osteosarcoma. Responses were evaluated by clinical, radiographic, angiographic, and pathologic parameters. Fifteen patients were randomized to receive MTX-CF and 15 to I/A-CDP. In the MTX-CF arm there were four responses (three complete responses, one partial response) whereas in the I/A CDP arm there were nine responses (seven complete responses, two partial responses). Two patients who failed MTX-CF and requested alternative treatment with I/A-CDP also responded. The total I/A-CDP response was 11/17.

Intraarterial Chemotherapy for Extremity Osteosarcoma and MFH in Adults

“…Ettinger et al [18] reported excellent results using postoperative CDDP and DOX in patients with nonmetastatic OGS. After the initiation of neoadjuvant chemotherapy, the most notable advances in survival rates involved intraarterial chemotherapy [28,29,41,48]. We hypothesized by using doseintensive, repetitive cycles of intraarterial cisplatin and intravenous doxorubicin to treat primary high-grade extremity OGS and MFH of bone, we would improve survival rates in adults compared to those in previously published studies.…”

“…Jaffe et al [28] utilized IA CDDP (150 mg/m 2 ) as a single agent every 2 to 3 weeks and reported 16 of 42 patients had at least 90% tumor necrosis. In another study led by Jaffe et al [29], IA CDDP was compared with IV high-dose methotrexate (HDM) as primary treatment for OGS. The response rate of patients treated with IA CDDP was higher (p = 0.065) to those treated with HDM (60% versus 27%).…”

“…Based on these observations, and in an attempt to improve the prognosis of patients with OGS and MFH, an individualized neoadjuvant approach was developed by the Extremities at Risk team using two active agents: dose-intensified intraarterial (IA) cisplatin (CDDP) in combination with intravenous (IV) doxorubicin (DOX) [7,12,28,29]. We repeatedly administered these two agents only.…”

Neoadjuvant Intracarotid Chemotherapy for Treatment of Advanced Adenocystic Carcinoma of the Lacrimal Gland

“…These tumors have demonstrated salutary response to cisplatin and doxorubicin therapy. 3 Intra-arterial delivery of chemotherapy is an accepted treatment for extremity osteosarcoma, [4][5][6] central nervous system tumors, [7][8][9][10] primary and metastatic liver [11][12][13] tumors, and breast cancer in selected patients. [14][15][16] The major advantage of intra-arterial drug infusion is the ability to administer a dose of therapeutic agent to the area of involvement through an undisturbed vascular system, resulting in a better therapeutic index ( Table 1).…”

Critical factors for the reversal of methotrexate cytotoxicity by folinic acid

“…High-dose MTX is followed by folinic acid (FA) rescue in order to increase the drug's therapeutic index. High-dose MTX with FA rescue has been administered in a wide variety of dosage schedules (Stoller et al, 1977;Bertino, 1981;Rosen et al, 1982;Evans et al, 1983;Jaffe et al, 1985). Based on these recent studies, FA rescue appears to vary as a function of the dose used and the time of rescue initiation after the start of MTX (between 8 to 36 h).…”