ESCALATING HIGH-DOSE CARBOPLATIN AND AUTOLOGOUS BONE-MARROW TRANSPLANTATION IN SOLID TUMORS

Twenty-seven patients with poor-prognosis malignancies were treated wi th a combination (CARBOPEC) of fixed-dose etoposide (1,750 mg/m(2)), c yclephosphamide (6,400 mg/m(2)), and escalating doses of carboplatin ( from 800 to 1,600 mg/m(2)) followed by autologous bone marrow transpla ntation (ABMT). All patients had previously received platinum derivati ves. The diagnoses were as follows: germ cell tumors (GCTs; n = 15); o varian carcinomas (n = 8); rhabdomyosarcomas (n = 3), and Hodgkin's di sease (n = 1). All 27 patients were fully evaluated for toxicity. The median duration of granulocytopenia (leukocytes <0.5 x 10(9)/1) and th rombocytopenia (platelets <20 x 10(9)/1) was 23 and 20 days, respectiv ely. Hematologic growth factors were used in 3 cases. The main nonhema tologic toxicity was gastrointestinal, with moderate to severe diarrhe a in 18 patients. No significant renal toxicity was observed. The over all response rate to this high-dose chemotherapy was 55%, with a compl ete response (CR) rate of 45% (9 patients). The median duration of CR was 9 months. Five of the 27 patients are alive with no evidence of di sease (NED) at 5, 22, 27, 40, and 43 months after ABMT. Four of the 11 patients with refractory GCTs have NED at 5, 22, 27, and 40 months, t ogether with 1 of the 3 responders (43 months). Our study shows the en couraging antitumor activity of this regimen. Similar chemotherapy sch edules have also been used with high response rates in GCT, ovarian ca ncer, breast cancer, and soft tissue sarcoma in children. The CARBOPEC protocol seems to be a good candidate for therapy intensification in patients with various malignancies. A European trial for salvage thera py in GCT will be activated in the near future. Moreover, results shou ld improve with the widespread use of hematopoietic growth factors and optimization of carboplatin administration that takes pharmacokinetic parameters into account.