Cost-effective treatment of women with advanced ovarian cancer by cytoreductive surgery and chemotherapy directed by an in vitro assay for drug resistance.
OBJECTIVE
Epithelial ovarian cancer is the fourth leading cause of cancer-related death in women. Five-year survival is about 25%, and new approaches to the treatment of this disease are dearly warranted. This study was designed to determine the feasibility of using an in vitro assay for drug resistance to guide treatment after cytoreductive surgery. We present preliminary results of this study after a median follow-up of 24 months.


METHODS
We treated 66 patients with advanced ovarian cancer by use of a combination of cytoreductive surgery and chemotherapy. Patient inclusion criteria included histologic confirmation of epithelial ovarian cancer, International Federation of Gynecology and Obstectrics (FIGO) stage III, no prior chemotherapy or radiation therapy, no coexisting neoplasm, and optimal residual disease (< 2 cm). Malignant tissue from the involved ovary of each patient was tested in vitro for drug resistance, and chemotherapy was directed individually by assay results. On the basis of the assay we treated 19 patients with platinum/paclitaxel (TP) and 47 with platinum/cyclophosphamide (CP).


RESULTS
Three-year survival (Kaplan-Meier estimate) was 69%; the 95% confidence interval was 58% to 80%. There was no difference in 3-year survival between the 19 patients treated with TP (66%) and the 47 patients treated with CP (74%). The cost-effectiveness of each treatment option was determined. It cost $4615 to achieve 3-year survival for patients receiving CP and $17,988 to obtain a similar survival with TP. The cost-effectiveness of assay-directed therapy was $9768.


CONCLUSIONS
Because of the high recurrence rate and the poor long-term survival of women with advanced ovarian cancer, improved therapies for this disease are needed. After surgical debulking, we used results of an in vitro assay for drug resistance to individually select chemotherapy for the patients in this study. Although the 3-year survival of 69% obtained in the present study appears good compared with previously published studies of optimally debulked patients, the results must be viewed with caution. Patients were not randomized, and differences in prognostic factors, such as tumor grade, patient age, and performance status, could account in part for the higher survival found in the current study compared with previously published studies. Treatment with either CP or TP resulted in equivalent 3-year survival. The cost to achieve 3-year survival with this protocol, including the cost of the drug resistance assay, was $9768. We believe that consideration of costs avoided by the elimination of ineffective treatments, needless toxicity, and loss of quality of life would likely increase the cost-effectiveness of assay-directed therapy compared with conventional therapy. This study demonstrates that it is feasible to use an in vitro assay in routine clinical practice to eliminate ineffective chemotherapeutic agents.
Orr
J W
JW
Patty Berg Cancer Center, Southwest Florida Regional Medical Center, Fort Myers 33901, USA.
Orr
P
P
Kern
D H
DH
D000970:Antineoplastic Agents / Q000191:economics / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003362:Cost-Benefit Analysis; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000191:economics / Q000401:mortality / Q000601:surgery*; D011446:Prospective Studies; D016019:Survival Analysis
D000970:Antineoplastic Agents