Orr J W, Orr P, Kern D H
Patty Berg Cancer Center, Southwest Florida Regional Medical Center, Fort Myers 33901, USA.
Cancer J Sci Am. 1999 May-Jun;5(3):174-8.
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.
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).
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.
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.
上皮性卵巢癌是女性癌症相关死亡的第四大主要原因。五年生存率约为25%，因此迫切需要治疗该疾病的新方法。本研究旨在确定使用体外耐药性检测来指导肿瘤细胞减灭术后治疗的可行性。我们报告了这项研究在中位随访24个月后的初步结果。
我们采用肿瘤细胞减灭术和化疗相结合的方法治疗了66例晚期卵巢癌患者。患者纳入标准包括上皮性卵巢癌的组织学确诊、国际妇产科联盟（FIGO）III期、既往未接受过化疗或放疗、无并存肿瘤以及最佳残留病灶（<2 cm）。对每位患者受累卵巢的恶性组织进行体外耐药性检测，并根据检测结果个体化指导化疗。根据检测结果，我们对19例患者采用铂类/紫杉醇（TP）方案治疗，对47例患者采用铂类/环磷酰胺（CP）方案治疗。
三年生存率（Kaplan-Meier估计值）为69%；95%置信区间为58%至80%。接受TP方案治疗的19例患者与接受CP方案治疗的47例患者的三年生存率无差异。确定了每种治疗方案的成本效益。接受CP方案治疗的患者实现三年生存的成本为4615美元，而接受TP方案治疗获得相似生存的成本为17,988美元。检测指导治疗的成本效益为9768美元。
由于晚期卵巢癌女性的高复发率和较差的长期生存率, 需要改进针对该疾病的治疗方法。在手术减瘤后，我们使用体外耐药性检测结果为该研究中的患者个体化选择化疗方案。尽管与先前发表的关于最佳减瘤患者的研究相比，本研究中获得的69%的三年生存率似乎较好，但结果必须谨慎看待。患者未进行随机分组，肿瘤分级、患者年龄和体能状态等预后因素的差异可能部分解释了本研究中观察到的生存率高于先前发表研究的原因。采用CP或TP方案治疗的三年生存率相当。采用该方案实现三年生存的成本，包括耐药性检测的成本，为9768美元。我们认为，考虑到通过消除无效治疗、不必要的毒性和生活质量下降所避免的成本，与传统治疗相比，检测指导治疗的成本效益可能会增加。这项研究表明，在常规临床实践中使用体外检测来排除无效化疗药物是可行的。
