Improved progression free survival (PFS), and rapid, sustained decrease in tumor perfusion among patients with advanced carcinoid treated with bevacizumab

Yao, J. C.; Ng, Chaan S.; Hoff, P. M.; Phan, Alexandra; Hess, Ken; Chen, H.; Wang, X.; Abbruzzese, J. L.; Ajani, Jaffer A.

doi:10.1200/jco.2005.23.16_suppl.4007

Cited by 39 publications

(15 citation statements)

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“…Efficacy varied by tumour histology with an ORR of 2% (1/41) among CT vs 13% (8/61) among ICC. In another phase II study where 44 patients with CT were randomised to bevazucimab or pegylated interferon, the former showed superior activity (4/22 vs 0/22 confirmed PR), reduction in tumour perfusion and improvement in PFS at 18 weeks (96% vs 68%) (Yao et al, 2005). However, neither of these two latter trials required evidence of progressive disease before study entry, therefore the patient populations are likely different from ours.…”

Section: Discussionmentioning

confidence: 72%

A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas

et al. 2006

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Standard cytotoxic treatments for neuroendocrine tumours have been associated with limited activity and remarkable toxicity. A phase II study was designed to evaluate the efficacy, safety and pharmacodynamics of temsirolimus in patients with advanced neuroendocrine carcinoma (NEC). Thirty-seven patients with advanced progressive NEC received intravenous weekly doses of 25 mg of temsirolimus. Patients were evaluated for tumour response, time to progression (TTP), overall survival (OS) and adverse events (AE). Twenty-two archival specimens, as well as 13 paired tumour biopsies obtained pretreatment and after 2 weeks of temsirolimus were assessed for potential predictive and correlative markers. The intent-to-treat response rate was 5.6% (95% CI 0.6 -18.7%), median TTP 6 months and 1-year OS rate 71.5%. The most frequent drug-related AE of all grades as percentage of patients were: fatigue (78%), hyperglycaemia (69%) and rash/desquamation (64%). Temsirolimus effectively inhibited the phosphorylation of S6 (P ¼ 0.02). Higher baseline levels of pmTOR (phosphorylated mammalian target of rapamycin) (P ¼ 0.01) predicted for a better response. Increases in pAKT (P ¼ 0.041) and decreases in pmTOR (P ¼ 0.048) after treatment were associated with an increased TTP. Temsirolimus appears to have little activity and does not warrant further single-agent evaluation in advanced NEC. Pharmacodynamic analysis revealed effective mTOR pathway downregulation.

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Section: Discussionmentioning

confidence: 72%

A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas

et al. 2006

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“…Bevacizumab, a mAbtargeting VEGF, and SU11248, a small-molecule tyrosine kinase inhibitor targeting the VEGF receptor, have both recently been shown to have single-agent activity in neuroendocrine tumors (28,29). Moreover, thalidomide was associated with apparent disease stabilization in a small phase II study of patients with metastatic neuroendocrine tumors (30).…”

Section: Discussionmentioning

confidence: 99%

Comparative Toxicity and Efficacy of Combined Radioimmunotherapy and Antiangiogenic Therapy in Carcinoembryonic Antigen–Expressing Medullary Thyroid Cancer Xenograft

Kraeber-Bodéré¹,

Bodet-Milin²,

Niaudet³

et al. 2010

J Nucl Med

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A significant antitumor effect was previously observed with radioimmunotherapy using anti-carcinoembryonic antigen 131 I-F6 monoclonal antibody in medullary thyroid cancer-bearing nude mice. Nevertheless, no complete response was observed. As seen with chemotherapy, drugs targeting the tumor microenvironment might improve radioimmunotherapy efficacy. This study evaluated the toxicity and efficacy of combining radioimmunotherapy with thalidomide or a cyclopeptidic vascular endothelial growth inhibitor (CBOP11) in mice grafted with the TT human medullary thyroid cancer cell line. Methods: Six to 10 nude mice treated with 92.5 MBq of 131 I-F6 in association with 200 mg/kg/d of oral thalidomide during 20 d by force-feeding or 0.45 mg/kg/d of CBOP11 during 25 d using subcutaneous minipumps were compared with control mice receiving either treatment or naked F6 or nonspecific 131 I-734. Combined therapies included 131 I-F6 at day 0 followed by thalidomide between days 20 and 40, thalidomide between days 0 and 20 followed by 131 I-F6 at day 25, 131 I-F6 at day 0 and CBOP11 between days 0 and 25, CBOP11 between days 0 and 25 followed by 131 I-F6 at day 25, and 131 I-F6 at day 0 followed by CBOP11 between days 20 and 45. Animal weight, hematologic toxicity, tumor volume, and serum calcitonin were monitored for the following 3 mo. Improvement of 125 I-F6 tumor biodistribution by antiangiogenic drug was studied after pretreatment by thalidomide. Follow-up of the tumor after combined antiangiogenic and radioimmunotherapy therapies was performed by histology studies. Results: Combined associations, as compared with radioimmunotherapy alone, increased leukopenia but not thrombocytopenia. Tumor volume-quadrupling time (TVQT) was 22.8 6 3.3 d in the control group, 29.9 6 3.6 d in the group treated with thalidomide, 34.6 6 4.4 d in the group treated with CBOP11, and 51.0 6 2.8 d after radioimmunotherapy alone. As compared with radioimmunotherapy, TVQT was significantly longer (P , 0.01) after thalidomide followed by radioimmunotherapy (69.83 6 3.9), CBOP11 followed by radioimmunotherapy (71.3 6 6.1), and CBOP11-radioimmunotherapy in concomitance (64.2 6 6.1). Nevertheless, TVQT was not increased after radioimmunotherapy followed by thalidomide (48.8 6 4) and radioimmunotherapy followed by CBOP11 (56.8 6 4.8). Surprisingly, pretreatment by CBOP11 or thalidomide sensitized larger tumors (.300 mm 3 ) to radioimmunotherapy. Change in calcitonin levels confirmed morphologic tumor response. Tumor uptake 24 h after injection of 125 I-F6 was 4.5 6 0.6 percentage injected dose per gram (%ID/g) without pretreatment and 8.7 6 1.3 %ID/g with pretreatment by thalidomide. An increase of the antitumor effect observed using the antiangiogenic drug combined with radioimmunotherapy was correlated with a decrease of blood vessels shown by von Willebrand immunostaining. Conclusion: Pretreatment with antiangiogenic therapies improved radioimmunotherapy efficacy, with acceptable toxicity. Future investigations will be performed to understand how antia...

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“…22 Bevacizumab, SU11248, a small molecular weight tyrosine kinase inhibitor targeting the VEGF receptor and thalidomide have recently been shown to have single-agent activity in neuroendocrine tumors. [23][24][25] Angiogenesis probably plays an important prognostic role in MTC. Indeed, a pathology study assessing 53 MTC patients observed that the number of newly formed vessels was significantly associated with poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse model of medullary thyroid carcinoma

Salaun

Bodet-Milin

Frampas

et al. 2010

Cancer

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2,3‐Diaryl substituted maleimides as model compounds of conjugated maleimide polymers [poly(RMI‐alt‐Ar) and poly(RMI‐co‐Ar)] were synthesized from 2,3‐dibromo‐N‐substituted maleimide (DBrRMI) [R= cyclohexyl (DBrCHMI) and n‐hexyl (DBrHMI)] and aryl boronic acid using palladium catalysts. To clarify structures of conjugated polymer containing maleimide units at the main chain, 13C NMR spectra of 2‐aryl or 2,3‐diaryl substituted maleimides were compared with those of N‐substituted maleimide polymers. Copolymers obtained with DBrRMI via Suzuki‐Miyaura cross‐coupling polymerizations or Yamamoto coupling polymerizations were dehalogenated structures at the terminal end. This dehalogenation may contribute to the low polymerizability of DBrRMIs. On the other hand, the π‐conjugated compounds showed high solubility in common organic solvents. The N‐substituents of maleimide cannot significantly affect the photoluminescence spectra of 2,3‐diaryl substituted maleimides derivatives. The fluorescence spectra of poly(RMI‐alt‐Ar) and poly(RMI‐co‐Ar) varied with N‐substituents of the maleimide ring. When exposed to ultraviolet light of wavelength 352 nm, a series of 1,4‐phenylene‐ and/or 2,5‐thienylene‐based copolymers containing N‐substituted maleimide derivatives fluoresced in a yellow to blue color. It was found that photoluminescence emissions and electronic state of π‐conjugated maleimide derivatives were controlled by aryl‐ and N‐substituents, and maleimide sequences of copolymers. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

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Improved progression free survival (PFS), and rapid, sustained decrease in tumor perfusion among patients with advanced carcinoid treated with bevacizumab

Cited by 39 publications

References 0 publications

A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas

A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas

Comparative Toxicity and Efficacy of Combined Radioimmunotherapy and Antiangiogenic Therapy in Carcinoembryonic Antigen–Expressing Medullary Thyroid Cancer Xenograft

Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse model of medullary thyroid carcinoma

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