Sustained response to bevacizumab in refractory well-differentiated ovarian neoplasms

Bidus, Michael A.; Webb, Joel C.; Seidman, Jeffrey D.; Rose, G. Scott; Boice, Charles R.; Elkas, John C.

doi:10.1016/j.ygyno.2006.03.048

Cited by 40 publications

(26 citation statements)

References 14 publications

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“…13 Of interest is the reported efficacy of bevacizumab in platinum-refractory ovarian carcinoma patients. 14,15 In our study, only a minority of patients (5.6%) received anti-VEGF therapy; further analysis of this small subgroup would be inadequate to determine any difference in benefit.…”

Section: Discussionmentioning

confidence: 87%

Modern systemic chemotherapy in surgically unresectable neoplasms of appendiceal origin

Shapiro¹,

Chase²,

Wolff³

et al. 2009

Cancer

111

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BACKGROUND: Appendiceal neoplasms include tumors ranging from benign-appearing cells with widespread mucin deposits to aggressive poorly differentiated signet ring cell adenocarcinomas. Traditionally, these tumors are treated with cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy. For some patients, cytoreductive surgery is not an option, and minimal published data exist in the management and outcome of these patients. A retrospective analysis was conducted to determine the benefit of modern systemic chemotherapy in patients with disseminated appendiceal neoplasm who were not considered optimal candidates for cytoreductive surgery. METHODS: A retrospective review was conducted using The University of Texas M. D. Anderson Cancer Center tumor registry between January 2000 and July 2005. Response was determined by radiographic response and/or overall clinical benefit. RESULTS: Of 186 patients diagnosed with appendiceal neoplasm, 54 (29%) patients considered to be suboptimal surgical candidates received 2 cycles of systemic chemotherapy. Thirty (55.6%) patients had a disease control rate noted as a complete response, partial response, or stable disease. After a median follow-up of 24 months, the median progression-free survival (PFS) and overall survival were determined to be 7.6 months (95% confidence interval [CI], 4-11) and 56 months (95% CI, 36-not applicable), respectively. CONCLUSIONS: Systemic chemotherapy has a role in appendiceal neoplasm patients who are suboptimal candidates for cytoreductive surgery. The intermediate PFS indicates the challenges that exist for appendiceal neoplasm patients in this setting. Prospective randomized trials including systemic chemotherapy are needed to provide further insight into this malignancy, for which no standard exists. Cancer 2010;116:316-22.

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Section: Discussionmentioning

confidence: 87%

Modern systemic chemotherapy in surgically unresectable neoplasms of appendiceal origin

Shapiro¹,

Chase²,

Wolff³

et al. 2009

Cancer

111

View full text Add to dashboard Cite

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“…Non-cytotoxic lowering of tumor cell apoptotic thresholds may prove uniquely useful in such clinical contexts [131]. For example, targeted attenuation of PI3K-Akt pathway signaling-not only via direct VEGF blockade [132] but via related growth factor receptor cascades, such as those mediated by EGF or HER2 [85]-may restore sensitivity to agents that have become ineffective after initial response. Notoriously resistant tumor types such as renal cell carcinoma [133]-as well as newer candidates including soft-tissue sarcoma [134], hepatocellular carcinoma [135], melanoma [94] and mesothelioma [136]-are therefore prime candidates for trials of anti-VEGF-containing drug cocktails.…”

Section: Chemosensitizationmentioning

confidence: 99%

VEGF signaling inhibitors: More pro-apoptotic than anti-angiogenic

Epstein

2007

Cancer Metastasis Rev

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The vascular endothelial growth factor (VEGF) family of polypeptide growth factors regulates a family of VEGF receptor (VEGFR) tyrosine kinases with pleiotropic downstream effects. Angiogenesis is the best known of these effects, but additional VEGF-dependent actions include increased vascular permeability, paracrine/autocrine growth factor release, enhancement of cell motility, and inhibition of apoptosis. In theory, therapeutic inhibition of angiogenesis should reduce tumor perfusion and thus increase tumor hypoxia and chemoresistance, but in clinical practice the VEGF antibody bevacizumab acts as a broad-spectrum chemosensitizer. Since VEGFR expression occurs in many tumor types, such chemosensitization is more readily explained by direct inhibition of tumor cell survival signals than by indirect stromal/vascular effects. The emerging model of anti-VEGF drug action being mediated primarily by tumoral (as distinct from endothelial) VEGFRs has clinically important implications for optimizing the anti-metastatic efficacy of this expanding drug class.

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“…126 Altretamine has a 14% response rate 127 and ifosfamide a 12% response rate, 128 although less information is available regarding their use in patients who are refractory to paclitaxel. Bevacizumab is also active (21%) in both platinum-sensitive and platinum-resistant patients, [129][130][131][132][133] although it may cause arterial thrombosis or intestinal perforation. Several trials are assessing combination therapy with bevacizumab for recurrent ovarian cancer (i.e., OCEANS, AURELIA).…”

Section: Recurrent Diseasementioning

confidence: 99%