Platinum-based chemotherapy is the cornerstone of treatment for patients with advanced ovarian cancer. A clinically important dose-response relationship has been demonstrated with platinum compounds. However, the delivery of high-dose carboplatin regimens has been limited by severe myelosuppression, particularly thrombocytopenia. The overall purpose of this study is to find the maximal tolerated dose of high-dose carboplatin in combination chemotherapy using peripheral blood stem cell (PBSC) support in previously untreated patients with advanced disease. The specific goals of this study are 1) Determine the safety and feasibility of dose-intense platinum-based chemotherapy in patients with advanced ovarian cancer. 2) Determine if PBSC support can ameliorate the hematologic toxicity encountered with high-dose carboplatin regimens. 3) Develop a regimen to be used in phase II trials. Data using stem cell support and high-dose chemotherapy in patients with ovarian cancer is scanty and mostly derived from heavily pretreated patients. In contrast, in the proposed trial, the patients will be previously untreated. The regimen will be further tested in future trials in patients with minimal disease after cytoreductive surgery and will form the basis for subsequent trials-involving high-dose carboplatin-taxol combinations. Additionally, laboratory studies are planned to: 1) Examine the correlation of CD34 + cells and granulocyte-macrophage colony-forming unit which serve as markers for stem cells. 2)Determine if the rapidity of data retrieval using flow cytometry would facilitate best timing of stem cell collection and replace clonogenic assays as the standard method of stem cell enumeration. 3) Establish the dose of CD34+ cells which predicts for rapid recovery of hematologic function as measured by days to recovery of white blood cells, granulocytes, platelets and hemoglobin. Other parameters will include the number of red blood cell and platelet transfusions and hospitalized days. Once it has been established that high-dose therapy can be safely administered, prospective randomized trials will be necessary to determine the effect upon survival.
| Schilder, R J; Johnson, S; Gallo, J et al. (1999) Phase I trial of multiple cycles of high-dose chemotherapy supported by autologous peripheral-blood stem cells. J Clin Oncol 17:2198-207 |
| Kotz, K W; Schilder, R J (1995) High-dose chemotherapy and hematopoietic progenitor cell support for patients with epithelial ovarian cancer. Semin Oncol 22:250-62 |
