DOSE-EFFECT STUDY OF CARBOPLATIN IN OVARIAN-CANCER - A DANISH OVARIAN-CANCER GROUP-STUDY

Purpose: To elucidate the effect of a doubled carboplatin dose-intensi ty in epithelial ovarian cancer in combination with a fixed dose of cy clophosphamide. Patients and Methods: A total of 222 patients with epi thelial ovarian cancer stages II to IV were included in the study. Fol lowing surgery, patients were randomly assigned to receive carboplatin at an area under the concentration-versus-time curve (AUG) of 4 (AUC4 ) or carboplatin at an AUC of 8 (AUC8) and cyclophosphamide 500 mg/m(2 ) given every 4 weeks for six courses. The AUC was calculated accordin g to Calvert's formula, In 123 patients, the carboplatin AUC was also measured based on a single-sample method and the results were compared with the calculated AUC. The end points of the trial were complete pa thologic remission (CPR) and crude survival. Results: Approximately 50 % of patients in both arms underwent second-look surgery. The frequenc y of CPR was 32% and 30%, respectively, The survival curves showed no significant difference (P = .84), The dose-intensity of cyclophosphami de was almost identical in the two arms,whereas that of carboplatin wa s different. In the AUC8 arm, the dose-intensity was 1.86 times that o f the AUC4 arm. The results also demonstrated good agreement between t he calculated and the measured AUC in most patients. Bone marrow toxic ity wets significantly higher in the AUC8 arm. Conclusion: A doubling of the carboplatin dose-intensity did not result in any significant im provement of pathologic remission or survival. Calvert's formula can b e used to give a fairly accurate estimate of the carboplatin AUC. Bone marrow toxicity increased with higher dose-intensity, and a further i ncrease of dose is only feasible with growth-factor or stem-cell suppo rt. (C) 1997 by American Society of Clinical Oncology.