Phase I/II trial of multicycle high-dose chemotherapy with peripheral blood stem cell support for treatment of advanced ovarian cancer

Abstract

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). Fortyeight 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 41 cm after surgery. Two courses of induction/mobilization therapy with cyclophosphamide (250 mg/m 2 ) and paclitaxel (250 mg/m 2 ) 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/m 2 ) with or without etoposide (1600 mg/m 2 ). 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 followup, 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.

Hematopoietic Stem Cells: Transcriptional Regulation, Ex Vivo Expansion and Clinical Application

“…Stem cell transplantation is also used as an adjuvant with other chemotherapeutic agents for treating cancer patients suffering from acute myeloid leukemia and high-grade lymphoma with the hope of replacing the endogenous healthy stem cells that were destroyed due to high dose of therapeutic regimens [181, 182]. Solid tumors such as those affecting pediatric patients (Wilm’s tumor, retinoblastoma, Ewing sarcoma of bone or germ cell tumors and ovarian cancers) were treated with the adjuvant hematopoietic stem cell therapy with high rate of survival and lower immunological graft rejection [183–185]. …”

Plasticity and Maintenance of Hematopoietic Stem Cells During Development

“…Despite of these deficiencies, HSCs are used in autologous or allogeneic transplantations for the treatment of malignancies, such as lymphoma and leukaemia as well as for autoimmune diseases and other blood-related disorders [158]. The combination of HSC transplants with high-dose of chemotherapy or ionizing radiation has found to be an alternative successful therapeutic strategy [166-168]. Several approaches have been adopted to improve the quality of life and to increase the life expectancy of patients with hematological malignancies.…”

Lessons learned from a decade of clinical trials of high-dose chemotherapy in ovarian cancer

“…A very similar study was performed by Frickhofen et al (18) in 48 women with newly diagnosed FIGO stage III or IV disease and more than 1 cm residual disease after surgery. Two cycles of induction/mobilization with cyclophosphamide (250 mg/m 2 ) and paclitaxel (250 mg/m 2 ) were given with collection of PBSC.…”