Phase I/II trial of multicycle high-dose chemotherapy with peripheral blood stem cell support for treatment of advanced ovarian cancer.
Ovarian cancer is chemosensitive, but most patients with advanced disease die from tumor progression. As 25% of the patients can be cured by chemotherapy, it is reasonable to evaluate high-dose chemotherapy (HDCT). Forty-eight patients with untreated ovarian cancer were entered in a multicenter phase I/II trial of multicycle HDCT. Median age was 46 (19-59 years); International Federation of Gynecology and Obstetrics-stage was III in 79% and IV in 21%; 31% had residual disease >1 cm after surgery. Two courses of induction/mobilization therapy with cyclophosphamide (250 mg/m2) and paclitaxel (250 mg/m2) were used to collect peripheral blood stem cells. HDCT consisted of two courses of carboplatin (area under curve (AUC) 18-22) and paclitaxel followed by one course of carboplatin and melphalan (140 mg/m2) with or without etoposide (1600 mg/m2). Main toxicity was gastrointestinal. Limiting carboplatin to AUC 20 and eliminating etoposide resulted in manageable toxicity (69% without grade 3/4 toxicity). One patient died from treatment-related pneumonitis. At 8 years median follow-up, median progression-free-survival (PFS) and overall survival (OS) is 13.3 and 37.0 months. Five-years PFS and OS is 18 and 33%. Multicycle HDCT is feasible in a multicenter setting. A European phase III trial based on this regimen is evaluating the efficacy of HDCT.
Frickhofen
N
N
Department of Hematology/Oncology, Universitätsklinikum Ulm, Ulm, Germany. norbert.frickhofen@hsk-wiesbaden.de
Berdel
W E
WE
Opri
F
F
Haas
R
R
Schneeweiss
A
A
Sandherr
M
M
Kuhn
W
W
Hossfeld
D K
DK
Thomssen
C
C
Heimpel
H
H
Kreienberg
R
R
Hinke
A
A
Möbus
V
V
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D016896:Treatment Outcome
D005047:Etoposide; D016190:Carboplatin; D017239:Paclitaxel; D008558:Melphalan