PHASE-I TRIAL OF HIGH-DOSE MELPHALAN, HIGH-DOSE ETOPOSIDE AND AUTOLOGOUS BONE-MARROW RE-INFUSION IN SOLID TUMORS - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP (ECOG) STUDY

The purpose of this work was to determine the maximum tolerated (phase II) dose of melphalan and etoposide that can be given in conjunction with autologous BM re-infusion in patients who have refractory or rela psed solid tumors. Twenty-six patients with refractory or relapsed bre ast cancer (n = 15), small cell lung cancer (n = 1), ovarian cancer (n = 3), colorectal cancer (n = 3) or malignant melanoma (n = 4) were en rolled and treated in this phase I study. Patients ranged in age from 31 to 60 years (median 44.5 years). Melphalan 180 mg/m(2) (60 mg/m(2)/ day for 3 consecutive days iv over 30 min) and etoposide 1200-3600 mg/ m(2) (400-1200 mg/m(2)/day for 3 consecutive days iv over 4 h) were gi ven followed by autologous BM infusion 60-72 h after completion of che motherapy. Ten patients received GM-CSF or G-CSF therapy after marrow re-infusion. Regimen-related toxicities included fever, pancytopenia, mucositis, nausea, vomiting, diarrhea, esophagitis, hepatic dysfunctio n and infection. Neutrophils recovered to > 500 x 10(6)/l and platelet s recovered to > 20 x 10(9)/l (without transfusions) a median of 17 da ys and 20.5 days after marrow infusion, respectively. Dose-limiting to xicity occurred at an etoposide dose of 3600 mg/m(2) since 4 of 6 pati ents treated at this dose level experienced grade 4 NCI Common Toxicit y Criteria (mucositis (n = 3) and infection (n = 1)). Complete respons es were noted in 7 patients (breast cancer (n = 5), colorectal cancer (n = 1) and melanoma (n = 1)); partial responses were observed in 5 pa tients. Melphalan 180 mg/m(2) and etoposide 3000 mg/m(2) is a potent h igh-dose chemotherapy regimen with significant antineoplastic activity , particularly for breast cancer, and has acceptable toxicity when adm inistered in conjunction with autologous BM re-infusion.