Randomized Phase II trial of two high-dose chemotherapy regimens with stem cell transplantation for the treatment of advanced ovarian cancer in first remission or chemosensitive relapse: a Southwest Oncology Group study.
OBJECTIVE
To evaluate response rates, progression-free survival (PFS), overall survival (OS), and toxicity of two high-dose chemotherapy regimens with stem cell rescue used to treat patients with recurrent or persistent stage III/IV ovarian cancer, with the goal of taking one forward into a Phase III comparison with conventional therapy.


METHODS
Patients under 65 with clinically or pathologically persistent disease after initial chemotherapy or those relapsing >6 months after a complete remission (CR) were randomized to CMC carboplatin (1500 mg/m(2)), mitoxantrone (75 mg/m(2)), and cyclophosphamide (120 mg/kg)], or CTC: [cisplatin (165 mg/m(2)), thiotepa (600 mg/m(2)), and cyclophosphamide (5625 mg/m(2))] with stem cell rescue.


RESULTS
Of 67 randomized, the 32 and 26 eligible in the CMC and CTC arms were matched including age (median 49), maximum tumor diameter, and disease status at transplant. Low-risk disease (maximum diameter disease <or= 0.5 cm and platinum sensitivity) was demonstrated in only approximately one-half of the patients. There were two treatment-related deaths in each arm. The median PFS was 13 and 8 months, respectively, for the CMC and CTC arms. The median OS was 29 and 22 months for the CMC and CTC arms. In a multivariate analysis of PFS, normal CA125 at transplant and CR to primary therapy were significant; for OS, normal CA125 and platinum sensitivity were significant.


CONCLUSIONS
The CMC regimen was the superior regimen. However, few patients were long-term progression-free survivors. A clinical CR to primary therapy and a normal CA125, seen in a minority of patients, were requirements for a favorable outcome.
Stiff
Patrick J
PJ
Loyola University Stritch School of Medicine, Maywood, IL 60153, USA. pstiff@lumc.edu
Shpall
Elizabeth J
EJ
Liu
P Y
PY
Wilczynski
Sharon P
SP
Callander
Natalie S
NS
Scudder
Sidney A
SA
Jazieh
Abdul-Rahman
AR
Samlowski
Wolfram
W
McCoy
Jason
J
Alberts
David S
DS
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D013852:Thiotepa / Q000008:administration & dosage
D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin; D008942:Mitoxantrone