The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy

Department of Gynecology and Obstetrics, Johann Wolfgang Goethe-University, Frankfurt am Main.
Annals of Oncology (Impact Factor: 6.58). 08/2012; 23(10):2605-2612. DOI: 10.1093/annonc/mds203
Source: PubMed

ABSTRACT Background Despite recent progress in the treatment of ovarian cancer, the majority of patients eventually relapse. There is little information on the effectiveness of chemotherapy in higher treatment lines. Patients and methods Characterization of the second to sixth line therapy and its effects on survival was carried out, based on data of n = 1620 patients from three large randomized phase III trials investigating primary therapy. Results Median progression-free survival (PFS) after the first, second, third, fourth and fifth relapse was 10.2 [95% confidence interval (CI) 9.6-10.7], 6.4 (5.9-7.0), 5.6 (4.8-6.2), 4.4 (3.7-4.9) and 4.1 (3.0-5.1) months, respectively. Median overall survival (OS) after the first, second, third, fourth and fifth relapse was 17.6 (95% CI 16.4-18.6), 11.3 (10.4-12.9), 8.9 (7.8-9.9), 6.2 (5.1-7.7) and 5.0 (3.8-10.4) months, respectively. The most frequent second and third line chemotherapy was platinum combination (n = 313, 24.5%) and topotecan (n = 118, 23.6%), respectively. Relapse treatment improved PFS and OS at the second to fourth recurrence, although frequently not performed according to the standard of care. In multivariate analysis, platinum sensitivity and optimal primary tumor debulking were revealed as independent prognostic factors for PFS up to third relapse. Conclusion A maximum of three lines of subsequent relapse treatment seems to be beneficial for patients with recurrent ovarian cancer. Optimal primary tumor debulking and platinum sensitivity remain independent prognostic factors even after more frequent relapses.

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    • "In women with a diagnosis of ovarian cancer, disease recurrence will eventually occur in 60 to 85% of cases within five years after primary treatment [1]. Intravenous chemotherapy with platinum compounds, taxanes, anthracyclines, gemcitabine, topotecan, and trabectedin in various combinations and sequences are the mainstay of recurrence treatment with median survival rates between 4 and 10 months [2]. Intraperitoneal chemotherapy (IPC) in the clinical setting of recurrent ovarian cancer is an experimental approach. "
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    ABSTRACT: To assess the activity of laparoscopic Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in women with recurrent, platinum-resistant ovarian cancer. Prospective case series using repeated courses q 28-42days of PIPAC containing cisplatin 7.5mg/m(2) and doxorubicin 1.5mg/m(2) at 12mmHg and 37°C for 30min. Objective tumor response was defined as tumor regression on histology and peritoneal carcinomatosis index (PCI) improvement on repeated video-laparoscopy. 34 PIPAC procedures were performed in 18 women, in 8 instances combined with cytoreductive surgery (CRS). Eight women had repeated PIPAC and objective tumor response was observed in 6 (complete remission:1; partial remission: 2; stable disease: 3). Five adverse events WHO grade ≥2 were noted, 3 of them after combined CRS. No perioperative mortality occurred. Median follow-up was 192days (min. 13 - max. 639). Cumulative survival after 400days was 62% and mean actuarial survival time was 442days. In a multivariable regression analysis with objective tumor response (yes vs. no) as the dependent variable and PIPAC (1 vs. >1), patient age (<75 vs. ≥75years), serum CA-125 (<1000 vs. >1000 U/mL), and presence of ascites (yes vs. no) as independent variables, PIPAC independently predicted objective tumor response. PIPAC has activity in women with recurrent, platinum-resistant ovarian cancer and should be investigated in prospective clinical trials.
    Gynecologic Oncology 11/2013; 132(2). DOI:10.1016/j.ygyno.2013.11.022 · 3.69 Impact Factor
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    ABSTRACT: Abstract Antiangiogenic and antilymphangiogenic gene therapy with soluble vascular endothelial growth factor receptor-2 (VEGFR-2) and soluble VEGFR-3 in combination with chemotherapy is a potential new treatment for ovarian carcinoma. We evaluated the safety, toxicology, and biodistribution of intravenous AdsVEGFR-2 and AdsVEGFR-3 combined with chemotherapy in healthy rats (n=90) before entering a clinical setting. The study groups were: AdLacZ and AdLacZ with chemotherapy as control groups, low dose AdsVEGFR-2 and AdsVEGFR-3, high dose AdsVEGFR-2 and AdsVEGFR-3, combination of low dose AdsVEGFR-2 and AdsVEGFR-3 with chemotherapy, combination of high dose AdsVEGFR-2 and AdVEGFR-3 with chemotherapy, and chemotherapy only. The follow-up time was 4 weeks. Safety and toxicology were assessed by monitoring the clinical status of the animals and by histological, hematological, and clinical chemistry parameters. For the biodistribution studies, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used. Low dose (2×10(10) vp) AdsVEGFR-2 and AdsVEGFR-3 gene therapy was well tolerated, even when gene therapy was combined with chemotherapy. Notably, only transient elevation of liver enzymes and mild regenerative changes were seen in liver after the gene transfer in the groups that received high doses (2×10(11) vp) of AdsVEGFR-2 and AdsVEGFR-3 with or without chemotherapy. No life-threatening adverse effects were noticed in any of the treatment groups. The highest protein concentration of soluble VEGFR-2 (sVEGFR-2) in circulation was seen 1 week after the gene transfer. The combination of chemotherapy to gene therapy seemed to prolong the time of detectable transgene protein at least 1 week in the circulation. The expression of AdsVEGFR-2 and AdsVEGFR-3 transgenes was mainly seen in the liver and spleen as detected by qRT-PCR. According to these results, AdsVEGFR-2 and AdsVEGFR-3 gene therapy combined with chemotherapy is safe and can be brought to clinical testing in ovarian cancer patients.
    03/2013; 24(1):29-37. DOI:10.1089/humc.2013.006
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