Chemosensitivity testing in gynecologic oncology--dream or reality?

Cell culture and animal models have played an essential role in the research of new principles of therapy. Many methods for the individualized testing of therapy sensitivity and resistance have been developed, for example, the clonogenic assay. Presently, the ATP-TCA is commercially available as a testing kit. This review gives an overview of the tumor samples that were tested in the oncologic laboratory in the Department of Obstetrics and Gynecology, Munich Grosshadern between 1993 and 2001. All target parameters show a clear trend in favor of sequential, dose-intensified Epirubicin/Paclitaxel therapy. If this trend remains valid for the total number of patients, a significant impact of this new principle of therapy can be expected. By individualized planning of therapy with ATP-TCA testing, therapy in the individual patient could already be performed by the examination of sensitivity in the preoperative biopsy specimen.

Dose-dense and sequential strategies in adjuvant breast cancer therapy.

Several attempts have been made to improve the survival rates of breast cancer patients. The benefit of adjuvant chemotherapy was clearly shown, but the absolute difference of 2% to 11% in overall survival, depending on the patient group, is disappointingly small. In particular, high-risk patients, such as those with > or = 10 involved lymph nodes, extracapsular spread, or vascular invasion, still have an excessive risk of recurrence even after standard adjuvant chemotherapy. To increase the survival rates after adjuvant therapy, new chemotherapeutic agents and new strategies of application are currently being evaluated in clinical trials. Chemotherapy with cyclophosphamide (Cytoxan, Neosar), methotrexate, and fluorouracil (CMF) seems to be safe and effective in patients with breast cancer. In addition, in metastatic patients, dose-intensified chemotherapy is being investigated. The introduction of epirubicin (Ellence), an agent less cardiotoxic and equally active compared to doxorubicin, enabled the escalation of anthracyclines in adjuvant therapy without serious cardiotoxic effects. The combination of dose-intensified chemotherapy and sequential application in the treatment of breast cancer is reviewed.

Correlation of drug response with the ATP tumorchemosensitivity assay in primary FIGO stage III ovarian cancer.

OBJECTIVE: Our purpose was to: (a) study the in vitro chemosensitivity of primary epithelial ovarian cancer to drug combinations with cisplatin (CDDP), carboplatin (CBDCA), paclitaxel (PTX), epirubicin (EPI), or cyclophosphamide (CTX) utilizing the ATP tumorchemosensitivity assay (ATP-TCA); (b) correlate the test results with clinical response in patients with FIGO stage III ovarian cancer; and (c) analyze the most useful parameters for interpretation of test results. METHODS: CBDCA/CTX, CBDCA/PTX, CDDP/PTX, and EPI/PTX were tested in 93 fresh human primary epithelial ovarian cancer specimens. Correlations of in vitro drug sensitivity/resistance and clinical response were performed in 38 patients with FIGO stage III disease utilizing Fisher's exact test and by comparison of progression-free (PFS) and overall survival (OS) between those testing as sensitive or resistant. A progression-free interval of more than 12 months following surgery was classified as clinical response. ATP-TCA results were analyzed using the median effective dose, area under the curve, or a defined sensitivity index. RESULTS: Evaluable test results were achieved in 83 of 93 patients (89%). EPI/PTX had the highest in vitro activity (P < 0.001). In the clinical correlation, 29 of 38 patients (76%) were classified as in vitro sensitive (sensitivity index [SI] <250) and 9 patients as in vitro resistant (SI >250). The SI was superior for interpretation of test results. Patients testing as chemosensitive had a significantly longer mean PFS (28.5 vs 12.6 months, P = 0.033) and OS (46.1 vs 17.6, P = 0.03) compared to those patients predicted to be resistant. The assay demonstrated a sensitivity, specificity, and positive and negative predictive value of 95, 44, 66, and 89%, respectively (Fisher's exact test, P = 0. 007). CONCLUSION: The observed in vitro efficacy of EPI/PTX in primary epithelial ovarian cancer specimens warrants further clinical evaluation. The high evaluability rate and the observed correlation with PFS and OS, within the limitations of a nonrandomized study, support the use of the ATP chemosensitivity assay in future prospective assay-directed trials.