Cis-platinum and ovarian carcinoma. In vitro chemosensitivity of cultured tumour cells from patients receiving high dose cis-platinum as first line treatment

Abstract

A study on the in vitro sensitivity of tumour cells from patients with ovarian cancer has been carried out in parallel with a clinical study designed to evaluate the role of high-dose cis-platinum (CIS) as first-line chemotherapy. A total of 50 samples from 102 patients have been successfully cultured and screened for in vitro chemosensitivity to 7 drugs, including CIS. The malignant nature of cells growing in culture was confirmed using a combination of karyology, morphology and immunohistochemical staining with HMFG2. Tumours were graded as sensitive (less than 40% of control 3H-leucine incorporation), intermediate (41-60% of control) or resistant (greater than 61% of control) to CIS. Correlation of in vitro sensitivity to cis-platinum with clinical response to cis-platinum assessed using CT scan and second-look laparotomy, showed positive correlation in 9/11 (89%) patients (8 = S/S; 1 = R/R); positive correlation between in vitro sensitivity to phosphoramide mustard and clinical response was also found in 4/6 patients receiving cyclophosphamide (3 = S/S; 1 = R/R). All patients with sensitive tumours showed a clinical response to cis-platinum. Comparison of cis-platinum sensitivity with sensitivity to phosphoramide mustard and melphalan showed that some tumours were sensitive only to cis-platinum; resistance to cis-platinum and sensitivity to phosphoramide mustard/melphalan was an infrequent occurrence. Some tumours which were resistant to cis-platinum showed sensitivity to adriamycin and bleomycin, particularly those from untreated patients. Sensitivity to 5-fluorouracil and resistance to cis-platinum was found in approximately equal proportions of tumours in both the treated and untreated groups.