Oral VP-16-213 in advanced bronchogenic carcinoma and toxic effects when combined with methotrexate.

Anderson, G. Brooke; Bowyer, Frank P.; Williams, L

doi:10.1136/thx.36.6.462

Cited by 8 publications

(1 citation statement)

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“…Studies attempting to measure mediators of bronchoconstriction have identified increases in arterial plasma histamine levels measured at the time of maximal airway narrowing to exercise (Anderson et al, 1981). Leukotriene E 4 (LTE 4 ) or the metabolite of prostaglandin D 2 , 9α,11β-PGF 2 , a marker of mast cell release, are measured in urine (Reiss et al, 1997; O’Sullivan et al, 1998b; Mickleborough et al, 2003) and sputum (Hallstrand et al, 2005) following EIB.…”

Section: Indirect Bronchial Provocation Testsmentioning

confidence: 99%

Airway Hyperresponsiveness in Asthma: Mechanisms, Clinical Significance, and Treatment

Brannan¹,

Lougheed²

2012

Front. Physio.

124

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Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of asthma. Bronchial provocation tests (BPTs) are objective tests for AHR that are clinically useful to aid in the diagnosis of asthma in both adults and children. BPTs can be either “direct” or “indirect,” referring to the mechanism by which a stimulus mediates bronchoconstriction. Direct BPTs refer to the administration of pharmacological agonist (e.g., methacholine or histamine) that act on specific receptors on the airway smooth muscle. Airway inflammation and/or airway remodeling may be key determinants of the response to direct stimuli. Indirect BPTs are those in which the stimulus causes the release of mediators of bronchoconstriction from inflammatory cells (e.g., exercise, allergen, mannitol). Airway sensitivity to indirect stimuli is dependent upon the presence of inflammation (e.g., mast cells, eosinophils), which responds to treatment with inhaled corticosteroids (ICS). Thus, there is a stronger relationship between indices of steroid-sensitive inflammation (e.g., sputum eosinophils, fraction of exhaled nitric oxide) and airway sensitivity to indirect compared to direct stimuli. Regular treatment with ICS does not result in the complete inhibition of responsiveness to direct stimuli. AHR to indirect stimuli identifies individuals that are highly likely to have a clinical improvement with ICS therapy in association with an inhibition of airway sensitivity following weeks to months of treatment with ICS. To comprehend the clinical utility of direct or indirect stimuli in either diagnosis of asthma or monitoring of therapeutic intervention requires an understanding of the underlying pathophysiology of AHR and mechanisms of action of both stimuli.

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Section: Indirect Bronchial Provocation Testsmentioning

confidence: 99%

Airway Hyperresponsiveness in Asthma: Mechanisms, Clinical Significance, and Treatment

Brannan¹,

Lougheed²

2012

Front. Physio.

124

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Phase II study of oral VP-16-213 in small cell lung cancer

Matsui

Oshima

Kado

et al. 1987

Cancer

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The soft, gelatin capsule of VP-16-213 (etoposide) was given orally and evaluated in a Phase II study of 56 patients with histologically confirmed small cell lung cancer. The drug was given in a dose of 200 mg/body/day orally for 5 consecutive days, and the courses were repeated every 3 to 4 weeks depending upon the individual patient recovery from myelosuppression. An overall objective response was obtained in 17 patients (30%), five previously treated (23%) and 12 untreated (35%). The median days for response after the start of treatment was 14 d (range, 5 to 64), and the median duration of response was 62 days (range, 28 to 278). The dose-limiting factor was leukopenia, while thrombocytopenia was also experienced. Gastrointestinal reactions to toxicity and alopecia were also observed, but they were not overwhelming. The study demonstrated that the VP-16-213 soft gelatin capsule given orally is effective against small cell lung cancer without clinical cross-resistance to other cytotoxic agents. Its usefulness in combination chemotherapy is thus suggested.

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Ergebnisse und Möglichkeiten der Behandlung beim kleinzelligen Bronchialkarzinom

Niederle¹

1985

Interdisziplinäre Therapie Des Bronchialkarzinoms

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Oral VP-16-213 in advanced bronchogenic carcinoma and toxic effects when combined with methotrexate.

Abstract: Forty-six patients with histologically confirmed lung cancer received treatment with the cytotoxic drug

Cited by 8 publications

References 1 publication

Airway Hyperresponsiveness in Asthma: Mechanisms, Clinical Significance, and Treatment

Airway Hyperresponsiveness in Asthma: Mechanisms, Clinical Significance, and Treatment

Phase II study of oral VP-16-213 in small cell lung cancer

Ergebnisse und Möglichkeiten der Behandlung beim kleinzelligen Bronchialkarzinom

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