Pulmonary toxicity from novel antineoplastic agents

Dimopoulou, Ioanna; Bamias, Aristotle; Lyberopoulos, Panagiotis; Dimopoulos, Meletios Α.

doi:10.1093/annonc/mdj057

Cited by 120 publications

(91 citation statements)

References 105 publications

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“…Acute and chronic distal symmetrical paresthesias (occasionally with autonomic and motor dysfunctions) characterize paclitaxel-induced neuropathic pain [2] , but the underlying etiologies and mechanisms are poorly elucidated. The concept that paclitaxel can activate mast cell and basophils is based on clinical observations of pruritus and allodynia in 30%-40% patients during the early use of paclitaxel [2,3] .…”

Section: Introductionmentioning

confidence: 99%

Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1

et al. 2016

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Aim: Severe painful sensory neuropathy often occurs during paclitaxel chemotherapy. Since paclitaxel can activate mast cell and basophils, whereas quercetin, a polyphenolic flavonoid contained in various plants, which can specifically inhibit histamine release as a mast cell stabilizer. In this study we explore whether quercetin could ameliorate paclitaxel-induced neuropathic pain and elucidated the underlying mechanisms. Methods: Quercetin inhibition on histamine release was validated in vitro by detecting histamine release from rat basophilic leukemia (RBL-2H3) cells stimulated with paclitaxel (10 μmol/L). In the in vivo experiments, rats and mice received quercetin (20, 40 mg·kg -1 ·d -1 ) for 40 and 12 d, respectively. Meanwhile, the animals were injected with paclitaxel (2 mg/kg, ip) four times on d 1, 3, 5 and 7. Heat hyperalgesia and mechanical allodynia were evaluated at the different time points. The animals were euthanized and spinal cords and dorsal root ganglions were harvested for analyzing PKCε and TRPV1 expression levels. The plasma histamine levels were assessed in rats on d 31. Results: Pretreatment with quercetin (3, 10, 30 μmol/L) dose-dependently inhibited excessive histamine release from paclitaxelstimulated RBL-2H3 cells in vitro, and quercetin administration significantly suppressed the high plasma histamine levels in paclitaxeltreated rats. Quercetin administration dose-dependently raised the thresholds for heat hyperalgesia and mechanical allodynia in paclitaxel-treated rats and mice. Furthermore, quercetin administration dose-dependently suppressed the increased expression levels of PKCε and TRPV1 in the spinal cords and DRGs of paclitaxel-treated rats and mice. Moreover, quercetin administration may inhibited the translocation of PKCε from the cytoplasm to the membrane in the spinal cord and DRG of paclitaxel-treated rats. Conclusion: Our results reveal the underlying mechanisms of paclitaxel-induced peripheral neuropathy and demonstrate the therapeutic potential of quercetin for treating this side effect.

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Section: Introductionmentioning

confidence: 99%

Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1

et al. 2016

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“…As lesões pulmonares por quimioterápicos acometem o parênquima pulmonar e as vias aéreas, porém a incidência da toxicidade pulmonar ainda é questionável devido às co-morbidades pulmonares que podem estar presentes, o uso concomitante ou prévio de outros medicamentos, o aspecto nodular gerado como efeito adverso que pode ser confundido com metástases e o fato do comprometimento intersticial apresentar padrão radiológico semelhante à carcinomatose linfática. 6,13 Geralmente o início de sinais e sintomas são semelhantes, entretanto há casos em que podem ocorrer de forma aguda ou vigorosa. Segundo Dimopoulou et al as manifestações clínicas mais frequentes consistem em dispneia e doença intersticial pulmonar.…”

Section: Discussionunclassified

“…Segundo Dimopoulou et al as manifestações clínicas mais frequentes consistem em dispneia e doença intersticial pulmonar. 13 As alterações fisiopatológicas advindas da quimioterapia ocorrem a partir do terceiro ciclo quimioterápico, por essse motivo, em nosso estudo, a amostra foi avaliada em média no quarto ciclo. 14 Em estudo de revisão de literatura, foi evidenciado que os aspectos clinicos, diagnósticos e terapêuticos das principais pneumopatias induzidas por fármacos, especificamente pela ciclofosfamida, mitomicina e o metotrexate, resultam em um padrão ventilatório restritivo associado à redução da difusão de monóxido de carbono.…”

Section: Discussionunclassified

Avaliação da função pulmonar em pacientes com câncer submetidos à quimioterapia

Vione

Wagner

Benelli

et al. 2016

Rev Epidemiol Control Infect

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Avaliação da função pulmonar em pacientes com câncer submetidos à quimioterapia Evaluation of the lung function in cancer patients undergoing to chemotherapy ABSTRACTBackground and Objective: Some neoplastic agents used in cancer treatment cause pulmonary toxicity and other important adverse effects, therefore, the present study aimed to evaluate the presence of obstructive lung disease (OLD), restrictive lung disease (RLD) or mixed in patients

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“…Patterns of DI-ILD are non-specific interstitial pneumonia, eosinophilic pneumonia, hypersensitivity pneumonitis, pulmonary fibrosis, or organizing pneumonia [9]. Early withdrawal of the causative drug will often lead to improvement or even cure of the ILD.…”

Section: Discussionmentioning

confidence: 99%

Life-threatening interstitial lung disease associated with trastuzumab: case report

Pepels

Boomars

Kimmenade

et al. 2008

Breast Cancer Res Treat

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A female patient with HER2 positive, metastatic breast cancer presented with pulmonary infiltrates, and a plural effusion dyspnoea after several months of trastuzumab treatment. She had been treated without complications with six courses of docetaxel and trastuzumab in combination with dexamethasone with partial remission of disease. Malignancy, infection and cardiomyopathy were excluded as causes of dyspnoea. Pleural and broncheoalveolar fluid analyses (BAL) showed eosinophils. A diagnosis of trastuzumab-induced pneumonitis was made. After treatment with steroids there was gradual clinical improvement and disappearance of infiltrates. Although a causative association between trastuzumab and this patient's pulmonary syndrome was not proven, the potential for this toxicity should be considered.

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Pulmonary toxicity from novel antineoplastic agents

Abstract: Clinicians should be aware of the potential of most novel antineoplastic agents to cause lung toxicity. A high index of suspicion is required if these are combined with other cytotoxic drugs or radiation.

Cited by 120 publications

References 105 publications

Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1

Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1

Avaliação da função pulmonar em pacientes com câncer submetidos à quimioterapia

Life-threatening interstitial lung disease associated with trastuzumab: case report

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