Long term follow-up of patients with recurrent ovarian cancer after Ad p53 gene replacement with SCH 58500
Long term follow-up of patients with recurrent ovarian cancer after Ad p53 gene replacement with SCH 58500
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DOI：
10.1038/sj.cgt.7700473
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发表时间：
2002-07-01
影响因子：
6.4
通讯作者：
Pegram, M
中科院分区：
文献类型：
--
作者：
Buller, RE;Shahin, MS;Pegram, M
目的：我们之前报道了用腺病毒载体SCH 58500替代p53基因治疗复发性卵巢癌患者的安全性、有效性和良好的CA125应答。本研究的目的是评估这些重度预处理患者在服用SCH 58500后的长期随访情况。方法：患者（n=36）在I期研究中接受单剂量SCH 58500治疗，或在I/II期研究中接受SCH 58500多个周期的多次闭合（MD）联合铂基化疗治疗。5例患者最初在单剂量组接受治疗，并重新入组MD组。在没有重新入组患者的情况下，MD组分别被评估为MD1组（n=19）和MD2组（n=24），其中包括MD组患者。仅接受单剂量组治疗的患者被指定为SD （n=12）。大多数患者在试验结束后接受了医生的额外化疗。目前的分析是回顾性序贯队列生存分析。结果：第一位患者于1997年3月治疗，最后一位患者于1998年9月完成SCH 58500。在诊断年龄、Karnofsky状态、诊断至SCH 58500间隔时间、既往化疗周期或方案、无铂间隔时间、铂难治性患者百分比、预处理CA125或最大肿瘤体积方面，组间无差异。两组在SCH 58500前的无化疗间隔均比SD组稍长。接受MD SCH 58500联合化疗的患者中位生存期为12-13.0个月，而接受SD SCH 58500治疗的患者中位生存期仅为5个月。MD治疗复发性疾病后20个月以上有10例长期存活，而SD SCH 58500治疗后只有2例长期存活。结论：在大量预处理的复发性卵巢癌患者中，12- 13.0个月的中位生存期优于在该疾病初始复发时接受紫杉醇治疗的个体的16个月中位生存期，并且是姑息性放疗或紫杉醇失败的5个月生存期的两倍以上。这些数据表明，对SCH58500的进一步研究是明确的。
Objective: We have previously reported the safety, efficient gene transfer, and favorable CA125 responses of individuals with recurrent ovarian cancer treated by p53 gene replacement with the adenoviral vector SCH 58500. The purpose of the present investigation was to evaluate the long-term follow-up of these heavily pretreated patients subsequent to SCH 58500 dosing. Methods: Patients (n=36) were treated with either single-dose SCH 58500 in the phase I study or with multiple closes (MD) of SCH 58500 over multiple cycles in combination of platinum-based chemotherapy in the phase I/II portion of the study. Five patients were initially treated in the single-dose group and re-enrolled in the MD group. The MD group was evaluated both without the re-enrolled patients as MD1 (n=19), and as MD2 (n=24), which included them. Patients who were only treated on the single-dose arm were designated as SD (n=12). Most patients received additional chemotherapy at the discretion of their physicians on completion of the trial. The current analysis is a retrospective sequential cohort survival analysis. Results: The first patient was treated in March 1997 and the last patient completed SCH 58500 in September 1998. There was no difference in age at diagnosis, Karnofsky performance status, interval between diagnosis to SCH 58500, prior cycles or regimen of chemotherapy, platinum-free interval, percent platinum refractory patients, pretreatment CA125, or largest tumor volume between groups. Both MD groups had a slightly longer chemotherapy-free interval before SCH 58500 than the SD group. Median survival of individuals who received MD SCH 58500 with chemotherapy was 12-13.0 months, compared to only 5 months for those treated with SD SCH 58500. There are 10 long-term survivors more than 20 months after MD treatment for recurrent disease compared to only 2 long-term survivors after SD SCH 58500. Conclusion: The 12- to 13.0-month median survival in a heavily pretreated population with recurrent ovarian cancer compares favorably to the 16-month median survival for individuals treated with paclitaxel at the time of initial recurrence of this disease and is more than double the 5-month survival seen with palliative radiotherapy or paclitaxel failure. These data suggest that further study of SCH58500 is clearly indicated.