A phase II trial of high-dose mitoxantrone, carboplatin, and cyclophosphamide with autologous bone marrow rescue for recurrent epithelial ovarian carcinoma: analysis of risk factors for clinical outcome.
Despite high initial response rates to platinum-based chemotherapy, most patients with advanced ovarian carcinoma die of drug-resistant disease. Drug resistance can be overcome in the hematologic malignancies and lymphomas with high-dose therapy and bone marrow transplantation (BMT) when used early, suggesting that this therapy may also be of value in ovarian carcinoma. As a prelude to the use of high-dose chemotherapy with BMT early in the management of advanced ovarian carcinoma, we evaluated a new high-dose regimen in patients with relapsed/refractory ovarian carcinoma to define toxicities and responses. Thirty patients were treated, of whom 20 were platinum resistant and 22 had > 1 cm maximum diameter disease. They received mitoxantrone (75 mg/m2), carboplatin (1500 mg/m2), and cyclophosphamide (120 mg/kg), followed by an autologous BMT. Overall, 89% responded, with clinical complete responses seen in 88 vs 47% (P = 0.06) of platinum-sensitive vs -resistant disease. There was only one early death (3.3%) due to Aspergillus pneumonia. Median survival for all 30 patients was 29 months, and at 3 years 23% are alive without disease. There was a 10.1- vs 5.1-month progression-free survival for patients with platinum-sensitive versus -resistant disease, and at a median follow-up of 12 months, 80% of the platinum-sensitive patients are alive. This regimen is safe, and for platinum-sensitive disease appears superior to other salvage therapies. Its use should be explored earlier in the management of advanced ovarian carcinoma.
Stiff
P
P
Department of Medicine, Loyola University Stritch School of Medicine, Maywood, Illinois 60153, USA.
Bayer
R
R
Camarda
M
M
Tan
S
S
Dolan
J
J
Potkul
R
R
Loutfi
S
S
Kinch
L
L
Sosman
J
J
Peace
D
D
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000628:therapy*; D011379:Prognosis; D012307:Risk Factors; D016879:Salvage Therapy; D016896:Treatment Outcome
D003520:Cyclophosphamide; D016190:Carboplatin; D008942:Mitoxantrone