A phase I study of daily everolimus plus low-dose weekly cisplatin for patients with advanced solid tumors

Fury, Matthew G.; Sherman, Eric J.; Haque, Sofia; Korte, Susan; Lisa, Donna; Shen, Ronglai; Wu, Nian; Pfister, David G.

doi:10.1007/s00280-011-1734-5

Cited by 48 publications

(36 citation statements)

References 34 publications

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“…Other regimens with reported efficacy in pulmonary carcinoid include liposomal doxorubicin + capecitabine (case report of a single patient with typical carcinoid and a partial response) [11], everolimus + cisplatin (of 3 patients with metastatic pulmonary carcinoid, partial response was seen in 2 patients with atypical disease and 1 patient had stable disease) [12], and navitoclax [25]. …”

Section: Discussionmentioning

confidence: 99%

“…stage IIB/IIIA) based on data showing a response rate of 20% to any chemotherapy [8], although this approach has been questioned by others who feel the role of systemic treatment is limited [9]. Regimens showing antitumor activity against pulmonary carcinoid tumors include octreotide [10], doxorubicin/capecitabine [11], everolimus + cisplatin [12], everolimus + octreotide [13], and etoposide + cisplatin [8]. The efficacy of adjuvant treatment for stages II and III resected typical and atypical carcinoid tumors is extrapolated from these response rates in metastatic disease, and the efficacy of adjuvant chemotherapy in resected stage II and III non-small cell lung cancer trials [14], [15] and [16].…”

Section: Introductionmentioning

confidence: 99%

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Chemotherapy for locally advanced and metastatic pulmonary carcinoid tumors

et al. 2014

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Objectives The optimal management of locally advanced and metastatic pulmonary carcinoid tumors remains to be determined. Materials and methods A retrospective review was conducted on patients with typical and atypical pulmonary carcinoid tumors treated at our institutions between 1990 and 2012. Results 300 patients were identified with pulmonary carcinoid, (80 patients with atypical carcinoid), of whom 29 presented with metastatic disease (16 atypical). Of evaluable patients, 26 (41%) with stages I–III atypical carcinoid tumors recurred at a median time of 3.7 years (range, 0.4–32), compared to 3 (1%) patients with typical carcinoid (range, 8–12.3). 39 patients were treated with chemotherapy, including 30 patients with metastatic disease (27 atypical), and 7 patients were treated with adjuvant platinum–etoposide chemoradiation (6 atypical, 1 typical, 6 stage IIIA, 1 stage IIB). At a median follow-up of 2 years there were 2 recurrences in the 7 patients receiving adjuvant treatment. Median survival after diagnosis of metastatic disease for patients with atypical pulmonary carcinoid was 3.3 years with a 5-year survival of 24%. Treatment regimens showing efficacy in pulmonary carcinoid include 15 patients treated with octreotide-based therapies (10% response rate (RR), 70% disease control rate (DCR), 15 month median progression-free survival (PFS)), 13 patients treated with etoposide + platinum (23% RR, 69% DCR, 7 month median PFS), and 14 patients treated with temozolomide-based therapies (14% RR, 57% DCR, 10 month median PFS). 8 of 10 patients with octreotide-avid disease treated with an octreotide-based regimen experienced disease control (1 partial response, 7 stable disease) for a median of 18 months (range 6–72 months). Conclusions These results support our previous finding that a subset of pulmonary carcinoid tumors are responsive to chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chemotherapy for locally advanced and metastatic pulmonary carcinoid tumors

et al. 2014

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“…We recently completed a phase I study of everolimus plus low-dose weekly cisplatin for patients with advanced solid tumors [11]. The favorable toxicity profile in that study suggests that it should be feasible to add paclitaxel to the mTORC1 inhibitor ?…”

Section: Introductionmentioning

confidence: 99%

A phase I study of temsirolimus plus carboplatin plus paclitaxel for patients with recurrent or metastatic (R/M) head and neck squamous cell cancer (HNSCC)

Fury

Sherman

et al. 2012

Cancer Chemother Pharmacol

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“…Por esta razão, diversos autores tem estudado os efeitos da inibição da via do mTOR em tumores de cabeça e pescoço (Fury et al, 2012;Molinolo et al, 2012;Sun et al, 2012), com resultados promissores. Em estudo clínico conduzido por Fury e colaboradores, a ação do inibidor de mTOR everolimus foi avaliada em uma série de pacientes com diferentes tipos de tumores sólidos, incluindo CECs de cabeça e pescoço.…”

Section: Discussionunclassified

“…Em estudo clínico conduzido por Fury e colaboradores, a ação do inibidor de mTOR everolimus foi avaliada em uma série de pacientes com diferentes tipos de tumores sólidos, incluindo CECs de cabeça e pescoço. Foi observada uma atividade anti-tumoral significativa neste grupo de pacientes, com redução ou estabilidade tumoral (Fury et al, 2012 Lippman e colaboradores, determinaram que para que um biomarcador possa ser considerado uma boa ferramenta diagnóstica, alguns fatores devem ser levados em consideração como a habilidade de se verificar a diferença entre um tecido normal e de alto risco; a possibilidade da identificação do mesmo em amostras com pequena dimensão; a capacidade de se estabelecer graduações ou padrões, e por fim, estudos preliminares clínicos que avaliem a relação destas proteínas com os agentes estudados (Lippman et al, 1990;Lee et al, 1992;Clark et al, 2010).…”

Section: Discussionunclassified

Análise comparativa da expressão imuno-histoquímica da via PI3K-AKT-mTOR em displasias epiteliais, lesões irritativas e carcinomas espinocelulares

Martins¹

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Clinical information regarding sex, age of the patient and location of the lesions were compiled. The slides (HE staining) were observed by two pathologists and all cases were re-evaluated under light microscope. The proteins investigated were: pAKT, pmTOR, PS6, and p4EBP1. The staining pattern of the antibodies was quantified by acquiring images using a photomicroscope. In the captured image (400x magnification), the total of counted labeled cells, were divided by the total number of cells present in the field captured. The staining pattern was classified into positive and negative and also divided into degrees starting from "0" to "3". The study variables were evaluated by chi-square test, ANOVA F and univariate logistic regression analysis. Among all the cases of MN, positivity was found only for pS6(50% of cases); in FH cases immunoreactivity was observed in pS6 (54.8% of cases) and 4EBP1 (22.6% of cases). In LRD immunoreactivity was observed in pS6 (67.4% of cases), pAKT (56.2% of cases), p4EBP1 (41.7% of cases) and pmTOR (29.2% of cases), while for HRD cases positivity was found for pS6 (74% of cases), pAKT (68% of cases), p4EBP1 (44% of cases) and pmTOR (28% of cases). In SCCs cases positivity was found for pAKT (83.3% of cases), PS6 (77.4% of cases), p4EBP1 (50% of cases) and pmTOR (50% of cases). Statistically significant differences were observed in all positive study groups for the proteins pAKT, pmTOR and p4EBP.After the evaluation of SCC and the oral dysplasia groups, there were statistically significant differences for the study groups that showed imunorretivity for the proteins pAKT and pmTOR. Therefore, we conclude that all the proteins of the study are good biomarkers to differentiate normal tissue from OD and SCC, but only pAKT and pmTOR proteins could be related to carcinogenesis.

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A phase I study of daily everolimus plus low-dose weekly cisplatin for patients with advanced solid tumors

Cited by 48 publications

References 34 publications

Chemotherapy for locally advanced and metastatic pulmonary carcinoid tumors

Chemotherapy for locally advanced and metastatic pulmonary carcinoid tumors

A phase I study of temsirolimus plus carboplatin plus paclitaxel for patients with recurrent or metastatic (R/M) head and neck squamous cell cancer (HNSCC)

Análise comparativa da expressão imuno-histoquímica da via PI3K-AKT-mTOR em displasias epiteliais, lesões irritativas e carcinomas espinocelulares

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