title: 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.
abstract: 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 relapsed solid tumors. Twenty-six patients with refractory or relapsed breast cancer (n = 15), small cell lung cancer (n = 1), ovarian cancer (n = 3), colorectal cancer (n = 3) or malignant melanoma (n = 4) were enrolled and treated in this phase I study. Patients ranged in age from 31 to 60 years (median 44.5 years). Melphalan 180 mg/m2 (60 mg/m2/day for 3 consecutive days i.v. over 30 min) and etoposide 1200-3600 mg/m2 (400-1200 mg/m2/day for 3 consecutive days i.v. over 4 h) were given followed by autologous BM infusion 60-72 h after completion of chemotherapy. 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 dysfunction and infection. Neutrophils recovered to > 500 x 10(6)/l and platelets recovered to > 20 x 10(9)/l (without transfusions) a median of 17 days and 20.5 days after marrow infusion, respectively. Dose-limiting toxicity occurred at an etoposide dose of 3600 mg/m2, since 4 of 6 patients treated at this dose level experienced grade 4 NCI Common Toxicity Criteria (mucositis (n = 3) and infection (n = 1)). Complete responses were noted in 7 patients (breast cancer (n = 5), colorectal cancer (n = 1) and melanoma (n = 1)); partial responses were observed in 5 patients. Melphalan 180 mg/m2 and etoposide 3000 mg/m2 is a potent high-dose chemotherapy regimen with significant antineoplastic activity, particularly for breast cancer, and has acceptable toxicity when administered in conjunction with autologous BM re-infusion.
authors.affiliation: Eastern Cooperative Oncology Group, Ireland Cancer Center, Case Western Reserve University.
authors.forename: H M
authors.initials: HM
authors.lastname: Lazarus
authors.forename: R
authors.initials: R
authors.lastname: Gray
authors.forename: N
authors.initials: N
authors.lastname: Ciobanu
authors.forename: J
authors.initials: J
authors.lastname: Winter
authors.forename: R S
authors.initials: RS
authors.lastname: Weiner
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000628:therapy; D012189:Retrospective Studies; D014182:Transplantation, Autologous
chemical_list: D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008558:Melphalan