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ABSTRACT: Background
Suppression of neoangiogenesis and pegylated liposomal doxorubicin (PLD) each contribute to the management of platinum-resistant/refractory ovarian cancer. The aim of this study is to test the combination of bevacizumab and PLD in women with resistant or refractory ovarian cancer.Methods
Eligibility criteria were no more than two prior treatments with platinum-containing regimens and one additional regimen, without anthracyclines. Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m(2)). The primary end point was progression-free survival (PFS) at 6 months; the secondary end points included side-effects, overall response rates (ORR) and survival (OS).ResultsForty-six patients were enrolled. The average number of courses administered was 7. The median PFS was 6.6 months (range 1-24.6 months) according to Gynecologic Cancer Intergroup Committee (GCIC) criteria and 7.8 months (range 2-13.3 months) according to Response Evaluation Criteria in Solid Tumors (RECIST). The median OS was 33.2 months (range 3-37.5+ months). The ORR was 30.2% [95% confidence interval (CI) 17.2-46.1] and the clinical benefit rate (CBR) was 86.1% (95% CI 72.1-94.7). Adverse events included mucosal and dermal erosions (30% grade 3) and asymptomatic cardiac dysfunction. Additional toxic effects included hypertension, headache, renal dysfunction and proteinuria, wound healing delay, and one episode each of central nervous system (CNS) ischemia and hemolytic uremic syndrome.ConclusionPLD with bevacizumab has improved activity in recurrent ovarian cancer with increased toxicity.
Annals of Oncology 07/2012; · 6.43 Impact Factor
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C F Verschraegen,
H Arias-Pulido,
S-J Lee,
S Movva,
L A Cerilli,
S Eberhardt,
B Schmit,
R Quinn, C Y Muller,
I Rabinowitz,
M Purdy,
D Snyder,
T Bocklage
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ABSTRACT: To assess the response of patients with soft tissue sarcoma (STS) to the combination of docetaxel, bevacizumab, and gemcitabine. Vascular endothelial growth factor (VEGF)-A levels and expression of VEGF-A and VEGF receptors 1 and 2 were evaluated.
Thirty-eight chemotherapy-naive patients with STS were enrolled. A dose-finding study for gemcitabine from 1000, 1250, then 1500 mg/m(2) was done in nine patients (three cohorts), followed by an expansion cohort of 27 patients. Dose of docetaxel was 50 mg/m(2), bevacizumab was 5 mg/kg, and gemcitabine was 1500 mg/m(2), every 2 weeks. Serum VEGF-A was measured by enzyme-linked immunosorbent assay and tissue VEGF-A and its receptors by immunohistochemistry.
The median follow-up was 36 months. The overall response rate observed was 31.4%, with 5 complete and 6 partial responses, and 18 stable diseases lasting for a median of 6 months. There was no significant hematologic toxicity. The adverse events with the highest grade were attributed to bevacizumab. There was no correlation of VEGF pathway biomarkers with outcome.
The combination of gemcitabine, docetaxel, and bevacizumab is safe and effective in patients with STS. The most concerning adverse events were consequences of bevacizumab administration. The benefit of bevacizumab in this patient population remains unclear.
Annals of Oncology 07/2011; 23(3):785-90. · 6.43 Impact Factor
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ABSTRACT: Epidermal growth factor receptor (EGFR) is overexpressed in the majority of cervical cancers (CCs). Somatic mutations of EGFR have been associated with clinical response to tyrosine kinase inhibitors (TKIs) in lung cancer patients. This study was designed to establish the frequency of EGFR point mutations in patients diagnosed with high-grade squamous intraepithelial lesions (HSIL) and CC. Nine cell lines derived from CC were screened for EGFR mutations in exons 18 through 21. Eighty-nine patient samples derived from invasive CC (n = 80) and HSIL (n = 9) were analyzed for the presence of EGFR mutations in exons 19 and 21. We found no mutations affecting the EGFR kinase domain in exons 18 through 21 in all cell lines tested, and no EGFR mutations were detected in exons 19 and 21 in all 89 human neoplastic samples analyzed. These data indicate that mutations in the EGFR kinase domain are very rare in CC and HSIL. Our results suggest, therefore, that treatment of CC patients with TKIs may not have the same efficacy as seen in patients with lung cancer, and that targeting the EGFR with other inhibitors may be more appropriate.
International Journal of Gynecological Cancer 11/2007; 18(4):749-54. · 1.65 Impact Factor
