Hensley M L, Hoppe B, Leon L, Sabbatini P, Aghajanian C, Chi D, Spriggs D R
Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.
Gynecol Oncol. 2001 Sep;82(3):464-9. doi: 10.1006/gyno.2001.6299.
In clinical practice, chemotherapy agents demonstrating modest second-line activity against platinum-refractory epithelial ovarian cancer (PROC) are frequently used in patients who have received multiple prior chemotherapy agents. Whether the response rates reported in selected patients can be expected in heavily pretreated patients is not known. Similarly, the costs of palliative chemotherapy are not known. We sought to determine the response, survival, and predictors of response in an unselected cohort of PROC patients receiving liposomal doxorubicin (LD) for relapsed disease, and the overall costs of delivering liposomal doxorubicin in this setting.
In a cohort of 62 consecutive patients who initiated LD as second- or greater-line therapy for PROC, the following variables were examined: age, number of prior regimens for relapse disease, duration of first clinical remission, time from last prior treatment, dose intensity of LD received, response/clinical benefit, time to progression, toxic effects, and survival. Multivariate analyses were used to identify predictors of clinical benefit and overall survival. Direct medical charges were calculated and converted to costs, and major cost drivers determined.
Sixty-two patients received a total of 174 cycles of LD. The mean number of cycles per patient was 2 (range, 1-8); the median number of prior regimens for recurrent PROC was 2 (range, 0-8); and the median duration of the first clinical remission was 6 months. Median dose intensity of LD delivered was 11.4 mg/m(2)/week (range, 2.8-16.7 mg/m(2)/week). Nine of sixty-two patients (14.5%) had an objective clinical response by CA-125 and/or CT scan (95% confidence interval, 6-23%). Grade 3/4 toxicity occurred in 11% of patients. In the full cohort, median time to progression was 2.2 months, and median overall survival, 9.6 months (range, 0.2-26 months). Dose intensity was the only independent predictor of overall response. Duration of first clinical remission and number of prior salvage regimens were associated with longer overall survival. The mean total direct medical cost per cycle of LD was $5763, and the major cost drivers were hospitalizations and drug acquisition/delivery costs.
LD is an active agent in PROC, even when used as greater-than-second-line therapy. Among heavily pretreated patients, delivering a dose intensity of at least 9.0 mg/m(2)/week was associated with a higher probability of response. The cost per cycle of LD is driven by hospitalizations and drug acquisition/delivery costs.
在临床实践中，对铂耐药上皮性卵巢癌（PROC）显示出适度二线活性的化疗药物常用于接受过多种先前化疗药物治疗的患者。目前尚不清楚在经过大量预处理的患者中是否能预期在选定患者中报告的缓解率。同样，姑息性化疗的费用也不清楚。我们试图确定在一组未选择的接受脂质体阿霉素（LD）治疗复发性疾病的PROC患者中的缓解情况、生存率及缓解预测因素，以及在这种情况下提供脂质体阿霉素的总体费用。
在一组62例连续将LD作为PROC二线或更高级别治疗起始方案的患者中，检查了以下变量：年龄、复发疾病的先前治疗方案数量、首次临床缓解持续时间、距上次先前治疗的时间、接受的LD剂量强度、缓解/临床获益情况、疾病进展时间、毒性作用和生存率。采用多变量分析来确定临床获益和总生存的预测因素。计算直接医疗费用并换算为成本，确定主要成本驱动因素。
62例患者共接受了174个周期的LD治疗。每位患者的平均周期数为2个（范围1 - 8个）；复发性PROC的先前治疗方案中位数为2个（范围0 - 8个）；首次临床缓解的中位数持续时间为6个月。LD的中位剂量强度为11.4mg/m²/周（范围2.8 - 16.7mg/m²/周）。62例患者中有9例（14.5%）通过CA - 125和/或CT扫描获得客观临床缓解（95%置信区间，6 - 23%）。11%的患者发生3/4级毒性反应。在整个队列中，疾病进展的中位时间为2.2个月，总生存的中位时间为9.6个月（范围0.2 - 26个月）。剂量强度是总体缓解的唯一独立预测因素。首次临床缓解持续时间和先前挽救治疗方案数量与更长的总生存相关。LD每个周期的平均总直接医疗成本为5763美元，主要成本驱动因素是住院费用和药品采购/配送成本。
LD在PROC中是一种有效的药物，即使用作二线以上治疗。在经过大量预处理的患者中，给予至少9.0mg/m²/周的剂量强度与更高的缓解概率相关。LD每个周期的成本由住院费用和药品采购/配送成本驱动。
