[Combined chemo- and hormone-therapy in advanced ovarian carcinoma--theoretical, experimental foundations and clinical results].

Abstract

The dissatisfying results achieved in the therapy of ovarian carcinoma with an unchanging low rate (between 10% and 30%) of five-year-survival were the reason for efforts to develop a new treatment scheme combining chemotherapy with hormone therapy for epithelial ovarian carcinoma in FIGO stages III and IV. Basic theoretical and experimental reflections: Although in many cases patients may show good response to standard chemotherapy containing cisplatin, a large percentage (70% to 90%) suffers a relapse due to the fact that single tumour cells are resistant to chemotherapy. In order to counteract this resistance we developed a method of therapy (in accordance with the ideas of Coldman and Goldie) based on the sequential application of various non cross-resistant cytostatic agents. This new regimen, comprised of Doxorubicin, Cisplatin, Vincristine, Cyclophosphamide and Methotrexate (AP-VC-MTX), was compared to two standard types of chemotherapy (Doxorubicin/Cyclophosphamide or Doxorubicin/Cisplatin) in a prospective, randomised study. The AP-VC-MTX regimen showed equal therapeutical results but had a significantly lower level of nephrotoxicity and gastrointestinal toxicity than the combined Doxorubicin/Cisplatin therapy. As a result of these studies we chose the AP-VC-MTX method as standard therapy for patients suffering from advanced stage ovarian carcinoma. Hormone therapy was tested in numerous phase II studies on patients who had previously received cytostatics and was found to be an effective alternative. One of the substances that was most closely studied was Medroxyprogesterone acetate (MPA). Its therapeutic value was established in in vitro tests which showed direct cytotoxicity in ovarian carcinoma and is based on the theory that, on the one hand, the MPA is attached to the progesterone receptor and impairs growth in a similar way to endometrium and breast carcinoma and, on the other hand, the MPA reduces the level of gonadotropin and estrogen, which may be factors, which stimulate tumour growth in ovarian cancer. Furthermore, the myeloprotective effect and the corticoid-like effect of the MPA usually result in lower bone marrow toxicity and an increase in weight. 81 in vitro chemosensitivity tests carried out on tumour-cell cultures of 25 patients suffering from ovarian carcinoma, showed sensitivity to Cisplatin in 38%, Doxorubicin in 44%, 4-OOH-Cyclophosphamide (the in vitro active metabolite of Cyclophosphamide) in 50%, Vincristine in 53%, MTX in 19% and MPA in 36%.(ABSTRACT TRUNCATED AT 400 WORDS)