Early stage ovarian cancer: a randomized clinical trial comparing whole abdominal radiotherapy, melphalan, and intraperitoneal chromic phosphate: a National Cancer Institute of Canada Clinical Trials Group report.

Abstract

Two hundred fifty-seven eligible patients with stage I, IIA "high risk" ovarian carcinoma and IIB, IIIO (disease confined to pelvis), were randomized to either total abdominal radiotherapy (arm A) 2,250 rad in 20 fractions (107 patients), melphalan (arm B) 8 mg/m2/d X 4 every 4 weeks X 18 courses (106 patients), or intraperitoneal chromic phosphate (arm C) 10 to 20 mCi (44 patients). All patients were initially treated with pelvic radiotherapy; arm A, 2,250 rad in ten fractions; and arms B and C, 4,500 rad in 20 fractions. Entry to arm C was discontinued early because of toxicity. In a multifactor analysis using proportional hazards models, no significant difference in survival was observed although there was a marginally significant difference in disease-free survival (P = .015) with arm B being superior to arm A. Stage (P less than .0001), grade (P less than .0001), and histology (P less than .008) were predictors of survival in the multifactor analysis. Performance status, age, and residual disease were significant predictors in the single factor analysis but were not predictive when correction was made for the effects of stage, grade, and histology. Five-year survival rates are 62% for arm A, 61% for arm B, and 66% for arm C. Median duration of follow-up is 8 years. Long-term complications of radiotherapy were seen in 19 patients on arm A, 11 on arm B, and 11 on arm C. Four patients who had received melphalan developed either a myelodysplastic syndrome or acute leukemia. Violations in covering the whole abdominal target volume were correlated with survival.

Coexpression of rat glutathione S-transferase A3 and human cytidine deaminase by a bicistronic retroviral vector confers in vitro resistance to nitrogen mustards and cytosine arabinoside in murine fibroblasts

“…Chlorambucil and Ara-C are part of an effective regimen for the treatment of low-grade non-Hodgkin's lymphomas; 34 high-dose melphalan and high-dose Ara-C are both active in advanced non-Hodgkin's lymphomas; 35,36 and finally, melphalan and gemcitabine are active against ovarian and breast cancers. [37][38][39][40] In addition, Ara-C, a drug that inhibits DNA repair, has been reported to enhance the cytotoxic activity of melpha-lan. 41 Hence, conferring chemoprotection against the hematotoxicity produced by nitrogen mustards and cytosine nucleoside analogs could potentially allow the safe use of desirable drug combinations that might otherwise cause unacceptable hematopoietic toxicity.…”

Systematic review of adjuvant therapy for early stage (epithelial) ovarian cancer

“…A surgical staging procedure was not described in the protocol of five trials and these studies have been excluded from the meta-analysis (15)(16)(17)(18)(19) (Table 2).…”

Adjuvant32P in the treatment of ovarian carcinoma

“…Those who had extensive adhesions at surgery were treated with whole abdominopelvic RT rather than 32 P. The overall incidence of bowel obstruction requiring surgery was 5%. The National Cancer Institute (NCI) Canada study [18] demonstrated significant bowel toxicity in patients who were treated with pelvic RT and 32 P; 9% of patients experienced small bowel obstruction, resulting in early closure of the treatment arm.…”