Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

53 patients with advanced and measurable cancerr were treated with vindesine in doses of 3 mg/m2 (pretreated) and 4 mg/m2 (non pretreated) i.v. once weekly. 48 patients are evaluable for response: of 14 patients with squamous cell carcinoma of the lung, 1 partial remission (PR), 1 minor response (MR) and 1 no change (NC) were observed. In 5 patients with large cell carcinoma of the lung: 1 NC. In 3 with adenocarcinoma of the lung: 1 MR. One patient with nasopharyngeal carcinoma had progressive disease. Stable disease was observed in a patient with carcinoma of the tongue and in a patient with adenocarcinoma of the esophagus. Four patients with colorectal carcinoma had progressive disease. One MR was observed in a patient with breast cancer, while all of the other 3 patients had progressive disease. One carcinoma of the penis was stable. One MR was observed in a patient with Hodgkin's disease. One PR was observed in a case with no-Hodgkin's lymphoma. A patient with acute leukemia had progressive disease. Among 9 patients with malignant melanoma, 3 had an MR and 1 patient had stable disease. A patient with fibrosarcoma had progressive disease. Observed toxicity included leukopenia, thrombocytopenia, anemia, paresthesias, constipation, jaw pain, nausea, stomatitis, alopecia, loss of taste, pruritus and skin rash, weakness and fatigue.
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PMID:[Phase-II-study with vindesine (desacetyl-vinblastine-amide-sulfate) in advanced malignant diseases]. 742 51

AE-941 (Neovastat), an antiangiogenic component extracted from cartilage, selectively competes for the binding of vascular endothelial growth factor to its receptor, inhibits matrix metalloproteinases, stimulates tissue plasminogen activator enzymatic activities, and induces apoptotic activities in endothelial cells. A phase I/II study was conducted to obtain information on its safety and efficacy in patients with advanced cancer refractory to treatment or for which no standard treatments were available. Eighty patients with histologically confirmed lung cancer were enrolled in a multicenter, open-label, dose-escalation study of AE-941 (30, 60, 120, or 240 mL/day) administered orally b.i.d. as monotherapy. No dose-limiting toxicity was reported. The most frequent adverse events were nausea (9%), pruritus (5%), anorexia (4%), and vomiting (4%). All adverse events were grade 1/2 except grade 3 constipation (n = 1). A survival analysis was conducted in the 48 patients with unresectable stage IIIA, IIIB, or IV non-small-cell lung cancer. A significant survival advantage was observed for patients receiving doses > 2.6 mL/kg/day (which correspond to approximately 180 mL/day in a 70-kg patient) compared to patients receiving lower doses (median, 6.1 months vs. 4.6 months; P = 0.026). No tumor responses were observed. On the other hand, 26% of the patients in the high-dose group had stable disease compared to 14% in the low-dose group. AE-941 is well tolerated in patients with advanced lung cancer. The higher dose of AE-941 explored in this phase I/II trial may confer a survival benefit.
Clin Lung Cancer 2003 Jan
PMID:Phase I/II trial of the safety and efficacy of AE-941 (Neovastat) in the treatment of non-small-cell lung cancer. 1462 12

Pemetrexed has recently been approved for use in combination with cisplatin as first-line chemotherapy for malignant pleural mesothelioma (MPM). Radiation therapy is frequently administered to the thoracic orifices and no data are available about the interactions between radiotherapy and pemetrexed. We report the first case of radiation recall dermatitis occurring after pemetrexed chemotherapy in a patient with MPM previously treated with radiation therapy to the thoracoscopy and drainage orifices. The patient received chemotherapy with pemetrexed and cisplatin 19 days after completion of chest wall radiation therapy delivering 21 gray in 3 days. Conventional premedication by folic acid and intramuscular administration of Vitamin B12 and prednisolone was correctly performed. Twelve days later, confluent erythematous and pruritus rash of the irradiated skin was observed. The toxicity grade of this lesion was evaluated at 2 according to the Acute Radiation Morbidity Scoring Criteria proposed by the Radiation Therapy Oncology Group. Pemetrexed challenge was performed without worsening of skin lesions. Three weeks later, skin cicatrisation was observed after a desquamative phase. Persistent hyperpigmentation was seen in the irradiated skin. Pemetrexed could also act as a radiosensitizing agent that should be used with care for several weeks after radiotherapy.
Lung Cancer 2005 Nov
PMID:Radiation recall dermatitis with pemetrexed. 1611 84

Many novel targeted agents have emerged against a variety of malignancies. Although papulopustular rash is the most commonly observed side effect associated with many of these agents, several non-rash skin toxicities have been identified that frequently result in the delay or discontinuation of anticancer therapy. These toxicities include skin hyperpigmentation, xerosis, pruritus, hair growth and color abnormalities, periungual and nail alterations, and hand-foot skin reaction. It is important to recognize these toxicities, so that they can be diagnosed early and treatment or dose modification can be initiated, if necessary. This review discusses several non-rash dermatologic toxicities observed with targeted therapeutic agents and guidelines for their diagnosis and treatment.
Clin Lung Cancer 2006 Dec
PMID:Non-rash skin toxicities associated with novel targeted therapies. 1723 89

Chronic inflammation has been strongly associated with tumor progression, but the underlying mechanisms remain elusive. Here we demonstrate that E3 ligase Itch and deubiquitinase Cyld formed a complex via interaction through 'WW-PPXY' motifs. The Itch-Cyld complex sequentially cleaved Lys63-linked ubiquitin chains and catalyzed Lys48-linked ubiquitination on the kinase Tak1 to terminate inflammatory signaling via tumor necrosis factor. Reconstitution of wild-type Cyld but not the mutant Cyld(Y485A), which cannot associate with Itch, blocked sustained Tak1 activation and proinflammatory cytokine production by Cyld(-/-) bone marrow-derived macrophages. Deficiency in Itch or Cyld led to chronic production of tumor-promoting cytokines by tumor-associated macrophages and aggressive growth of lung carcinoma. Thus, we have identified an Itch-Cyld-mediated regulatory mechanism in innate inflammatory cells.
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PMID:The E3 ligase Itch and deubiquitinase Cyld act together to regulate Tak1 and inflammation. 2208 10

Erlotinib is a selective epidermal growth factor receptor(EGFR)tyrosine kinase inhibitor, which shows favorable antitumor activity against chemorefractory lung carcinoma, especially with EGFR gene mutations. We experienced a case in which oxy- genation and performance status improved in with low-dose erlotinib of 100mg/day administered every other day incidental- ly, although a dose of erlotinib 150mg/day daily is encouraged by the RECIST guideline. A 77-year-old male was diagnosed with bronchioloalveolar carcinoma(BAC)and given first-line combination chemotherapy of carboplatin and pemetrexed. However, antitumor activity was not satisfactory. His performance status(PS)was scored as 2 and home oxygen therapy (HOT)was introduced. As second-line chemotherapy, erlotinib was administered 100mg/day daily. However, the patient took the medication every other day at his own discretion, due to severe eruption and itching sensation. Since this case is classified as a nonmeasurable lesion according to the RECIST guideline, it was difficult to measure antitumor activity by tumor size. But improvement of oxygenation, with a performance status score of 0 and normalization of serum CEA level suggested that erlonitib administration of 100mg/day every other day showed antitumor activity.
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PMID:[A case of bronchioloalveolar carcinoma successfully treated with low-dose, alternate-day administration of erlotinib]. 2242 74

Maintenance therapy, commenced immediately after the completion of first-line chemotherapy, is a promising strategy for improving treatment outcomes in patients with non-small-cell lung cancer (NSCLC). The global phase III SequentiAl Tarceva in UnResectable NSCLC (SATURN) study evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib as maintenance treatment in NSCLC patients without progression after first-line chemotherapy. We report a retrospective subanalysis of Asian patients enrolled in SATURN. Patients with advanced NSCLC with no evidence of progression after four cycles of chemotherapy were randomized to receive erlotinib 150 mg/day or placebo, until progressive disease or limiting toxicity. The co-primary endpoints of SATURN were progression-free survival (PFS) in all patients and in those with positive EGFR immunohistochemistry (IHC) status. Secondary endpoints included overall survival (OS), disease control rate, safety, quality of life (QoL) and biomarker analyses. In total, 126 patients from East and South-East Asian centers were randomized (14% of the intent-to-treat population): 88 from Korea, 28 from China and 10 from Malaysia; one patient was excluded from this analysis due to Indian ethnicity. PFS was significantly prolonged in the erlotinib treatment arm, both overall (hazard ratio [HR]: 0.57; p=0.0067) and in patients with EGFR IHC-positive disease (HR=0.50; p=0.0057). There was a trend towards an increase in OS, which reached statistical significance in the EGFR IHC-positive subgroup (p=0.0233). The overall response rate was significantly higher with erlotinib compared with placebo (24% versus 5%; p=0.0025). Erlotinib was generally well tolerated and had no negative impact on QoL in this subpopulation. The most common treatment-related adverse events were rash, diarrhea and pruritus. Erlotinib was effective and well tolerated in Asian patients, producing benefits consistent with those observed in the overall SATURN population. Maintenance treatment with erlotinib appears to be a useful option for the management of Asian patients with advanced NSCLC without progression after first-line chemotherapy.
Lung Cancer 2012 Aug
PMID:Efficacy and safety of maintenance erlotinib in Asian patients with advanced non-small-cell lung cancer: a subanalysis of the phase III, randomized SATURN study. 2249 67

Paraneoplastic syndromes are a group of rare disorders involving non-metastatic systemic effects accompanying malignancies, and occur remotely from the tumor itself. Chronic pruritus lasting more than 6 weeks can be from paraneoplastic origin. A 65-year-old woman was admitted for generalized pruritus lasting for 1 month, despite treatment with prednisolone, levocetirizine and hydroxyzine. General examination was normal. Biological data and gastroscopy were normal. One month later, the patient was readmitted for worsening of her pruritus and walking impairment, revealing a severe sensory neuropathy. Blood anti-Hu antibodies returned positive at a level of 400 (normal <100). Bronchoscopy and bronchial biopsies revealed small-cell lung carcinoma. To our knowledge, the association of generalized pruritus and paraneoplastic neuropathy has been rarely reported. Our observation raises the question of a pathophysiological continuum between pruritus and neuropathy in a paraneoplastic context.
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PMID:Generalized pruritus preceding paraneoplastic neuropathy. 2663 89

Although substantial progress has been made in the treatment of non-small-cell lung cancer (NSCLC) patients with immune checkpoint inhibitors (ICIs), severe immune-related adverse events (irAEs) sometimes occur. Here, we report a case of severe refractory pruritus after Stevens-Johnson syndrome (SJS) in a patient with NSCLC treated with nivolumab. The patient was a 76-year-old Japanese woman with advanced NSCLC treated with nivolumab. After the second dose, she experienced severe rash with mucous involvement. We diagnosed SJS and started 50mg of oral prednisolone (1mg/kg). The rash completely resolved after prednisolone was started, but we could not manage the severe pruritus with emollients, antihistamines, and steroids. Finally, we administered aprepitant, an oral neurokinin-1 receptor antagonist, for her refractory pruritus. Her symptoms improved within 5days. Severe refractory pruritus can arise from ICIs, and aprepitant may be a useful treatment.
Lung Cancer 2017 07
PMID:Aprepitant for refractory nivolumab-induced pruritus. 2857 51

An 85-year-old man was being treated for advanced squamous cell lung carcinoma with nivolumab as a second-line treatment. From the beginning of the third course, erythema appeared on his trunk and gradually progressed. Around the start of the fifth course, erythema spread to the proximal part of all limbs in addition to the trunk and was accompanied by a strong itching sensation. He was diagnosed as having contact dermatitis by a dermatologist because his rash was observed only where the moisture-absorbing fiber material of his underwear made contact with the skin surface. After suspending treatment of nivolumab, changing his underwear to a cotton material, and using moisturizers and steroid ointments, his rash disappeared in about a month and the size of his lung tumors remained reduced. The patient developed contact dermatitis despite the use of similar underwear without any skin problems for several years. We speculated that nivolumab-induced T-cell activation may have occurred in his skin, making him more likely to develop contact dermatitis, whose onset is thought to involve T-cell activation. No cases of contact dermatitis have been reported previously although the frequency of eruption as an immune-related adverse event is relatively high. When using immune checkpoint inhibitors including nivolumab, clinicians need to pay attention to the occurrence of skin disorders related to T-cell activation.
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PMID:Nivolumab-induced contact dermatitis in a patient with advanced lung cancer. 3257 73


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