Adjuvant treatment for early ovarian cancer: a randomized phase III trial of intraperitoneal 32P or intravenous cyclophosphamide and cisplatin--a gynecologic oncology group study.
OBJECTIVE
To conduct a prospective study of intraperitoneal radioactive chromic phosphate (32P) versus cyclophosphamide-cisplatin (CP) in women with early ovarian cancer at high risk for recurrence (International Federation of Gynecology and Obstetrics stage Ia or Ib grade 3 or Ic or stage II, no macroscopic residual disease) and to compare cumulative incidence of recurrence, overall survival, and relative toxicity.


METHODS
A total of 251 patients were randomly assigned to treatment with 32P or CP. Twenty-two (8.7%) were ineligible following centralized pathology review. Of the 229 patients included in the analysis, 110 received 32P, and 119 received CP.


RESULTS
The cumulative incidence of recurrence at 10 years was 35% (95% CI, 27% to 45%) for patients receiving 32P and 28% (95% CI, 21% to 38%) for those receiving CP. Patients receiving CP had a recurrence rate 29% lower than that of those receiving 32P (P =.15, two-tail test). The death rate for patients treated with CP was 17% lower than that for patients treated with 32P (difference not significant). Combining both arms, the 10-year cumulative incidence of recurrence for all stage I patients was 27% (95% CI, 20% to 34%) compared with 44% (95% CI, 32% to 56%) for stage II patients (P =.01). Both regimens were reasonably well tolerated, but problems with inadequate distribution (7%) and small-bowel perforation (3%) make the otherwise less toxic 32P less acceptable.


CONCLUSIONS
Although there are no statistically significant differences in survival, the lower cumulative recurrence seen with CP and complications of 32P administration make platinum-based combinations the preferred adjuvant therapy for early ovarian cancer patients at high-risk for recurrence.
Young
Robert C
RC
Gynecologic Oncology Group, Administrative Office, Four Penn Center, 1600 John F. Kennedy Blvd, Suite 1020, Philadelphia, PA 19103, USA. rc_young@fccc.edu
Brady
Mark F
MF
Nieberg
Roberta K
RK
Long
Harry J
HJ
Mayer
Allan R
AR
Lentz
Samuel S
SS
Hurteau
Jean
J
Alberts
David S
DS
D002288:Adenocarcinoma, Mucinous / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018269:Carcinoma, Endometrioid / Q000401:mortality / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D017608:Chromium Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018284:Cystadenocarcinoma, Serous / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D010710:Phosphates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010761:Phosphorus Radioisotopes; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
D017608:Chromium Compounds; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D003520:Cyclophosphamide; C509369:chromic phosphate; D002945:Cisplatin