title: Chemotherapy with maximally tolerable doses of VP 16-213 and cyclophosphamide followed by autologous bone marrow transplantation for the treatment of relapsed or refractory germ cell tumors.
abstract: Eleven patients with advanced nonseminomatous germ cell tumors (NSGCT), who relapsed after or were refractory to standard dose cisplatin-based remission induction chemotherapy, were treated in a phase II clinical trial with VP 16-213 2500 mg/m2 and cyclophosphamide 7 g/m2. Both drugs were given in maximally tolerable doses regarding extramedullary toxicity. Urothelial damage due to cyclophosphamide was prevented by the administration of mesnum. Autologous bone marrow was infused on day 7 to prevent long lasting medullary toxicity. Because of the disappointing results in the first three patients, a second treatment step was added. The next eight patients were treated with 2500 mg/m2 VP 16-213 divided and given on days 1-2-3 and after full bone marrow recovery with total doses of VP 16-213 2000 mg/m2 plus cyclophosphamide 7 g/m2 divided and given on days 29-30-31, followed by autologous bone marrow transplantation (ABMT) on day 35. Toxicity to high-dose VP 16-213 plus cyclophosphamide followed by ABMT consisted of mucositis, nausea, vomiting and diarrhea. No cardiac toxicity or hemorrhagic cystitis occurred. The mean duration of leukopenia and thrombopenia was 14 and 13 days respectively. The additional, preceding treatment with VP 16-213 as a single agent caused mucositis, and leukopenia and thrombopenia for a mean number of 9 and 6 days respectively. Seven responses were obtained: two complete responses of 46 and 66+ weeks respectively and five partial responses with a median response duration of 12 weeks. The median survival time was 40 weeks. This regimen of one or two courses with maximally tolerable doses of VP 16-213 plus cyclophosphamide and ABMT is not sufficient to salvage a substantial number of patients with relapsing or refractory NSGCT.
authors.affiliation: Department of Internal Medicine, University Hospital Groningen, The Netherlands.
authors.forename: P O
authors.initials: PO
authors.lastname: Mulder
authors.forename: E G
authors.initials: EG
authors.lastname: de Vries
authors.forename: H S
authors.initials: HS
authors.lastname: Koops
authors.forename: T
authors.initials: T
authors.lastname: Splinter
authors.forename: A
authors.initials: A
authors.lastname: Maas
authors.forename: S
authors.initials: S
authors.lastname: van der Geest
authors.forename: N H
authors.initials: NH
authors.lastname: Mulder
authors.forename: D T
authors.initials: DT
authors.lastname: Sleijfer
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004341:Drug Evaluation; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D009061:Mouth Mucosa; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*; D013280:Stomatitis / Q000139:chemically induced; D013736:Testicular Neoplasms / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide