Phase II trial of high-dose intravenous doxorubicin, etoposide, and cyclophosphamide with autologous stem cell support in patients with residual or responding recurrent ovarian cancer

Abstract

Summary:This study was performed in order to evaluate the toxicities, progression-free and overall survival of patients with responsive residual or recurrent ovarian cancer treated with high-dose chemotherapy. Twenty-seven patients were treated. Doxorubicin, 165 mg/m 2 over 96 h (days −12 to −8), etoposide 700 mg/m 2 every day ×3 (days −6 to −4), and cyclophosphamide 4.2 g/m 2 on d −3 was followed by stem cells and granulocyte colonystimulating factor. The median days of granulocyte count Ͻ500/ l was 14 (range 10-42) and platelets Ͻ20 000/ l was 13 (range 2-80). Median numbers of red cell and platelet transfusions were 15 (5-16) and 14 (4-103). Toxicity included mucositis requiring narcotic analgesia in all patients. Asymptomatic decreases in ejection fraction to values Ͻ50% were observed in four patients. No clinical congestive heart failure was observed. One death due to sepsis was observed. Median progression-free survival is 7.5 months (1.0-56 months); five patients remain alive, two of whom remain progression-free at 19.5 and 24.5 months post transplant. Median overall survival is 14.0 months (1-68 months). We conclude that high-dose anthracyclines may be safely administered to ovarian cancer patients. The short overall and progression-free survivals observed in our population suggest that this combination is not optimal. Bone Marrow Transplantation (2001) 28, 859-863.

Clinical Pharmacology of Cyclophosphamide and Ifosfamide

“…CPA is the most widely used alkylating agent in the treatment for hematological malignancies and a variety of solid tumors, including leukemia [12,13,285], breast cancer [286][287][288][289][290][291], lung cancer [292][293][294][295], lymphomas [296][297][298], prostate cancer [299,300], ovarian cancer [301][302][303][304][305][306], and multiple myeloma [307,308]. Although its role in the treatment for ovarian cancer and small-cell lung cancer is declining, CPA continues to be used in treatment of breast cancer as a critical component of the CMF, CEF (CPA, epirubicin, and 5-fluorouracil), MVC (mitoxantrone, vinblastine, and CPA) and TAC (docetaxel, doxorubicin and CPA) regimen [289,290,[309][310][311][312].…”

Post-operative sequential high-dose chemotherapy with haematopoietic stem cell support as front-line treatment in advanced ovarian cancer: a phase II multicentre study

“…HDC was originally developed in ovarian cancer as consolidation or salvage therapy in patients with prior conventional chemotherapy. 7,8,[23][24][25][26][27][28][29][30] Moreover, only a limited number of patients received this strategy as firstline treatment, essentially as consolidation after induction treatment. 8,13,23,28,31 Addressing this issue, the French GINECO group performed a randomised study evaluating the impact of a single course of HDC with autologous stem cell support as consolidation in AOC with low tumour burden following initial conventional chemotherapy, compared to 3 additional conventional chemotherapy cycles.…”

Evidence for a graft-versus-tumor effect in refractory ovarian cancer

“…Although up to 70% of patients with recurrent ovarian cancer achieve a second remission after HDT and autologous HSCT (Stiff et al 2000;Bojko et al 2001), the median progression-free survival was reported to be only 7-9 months (Morgan et al 2001;Rosti et al 2002;Bojko et al 2002). In summary, only 10-13% of patients transplanted for recurrent ovarian cancer remain longterm disease-free (Holmberg et al 1998;Shinozuka et al 1999;Stiff et al 2000).…”