Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PTK787/ZK 222584 (PTK/ZK) is an oral angiogenesis inhibitor targeting vascular endothelial growth factor (VEGF) receptor tyrosine kinases, including VEGFR-1/Flt-1, VEGFR-2/KDR, VEGFR-3/Flt-4, the platelet-derived growth factor receptor tyrosine kinase and the c-kit protein tyrosine kinase. The objective of this Phase I study was to evaluate the safety, tolerability, biologic activity and pharmacologic profile of PTK/ZK administered orally, twice daily, on a continuous dosing schedule in patients with primary refractory or relapsed acute myeloid leukemia (AML), secondary AML, poor-prognosis de novo AML or advanced myelodysplastic syndrome (MDS). Acute myeloid leukemia patients for whom PTK/ZK monotherapy was ineffective could receive PTK/ZK combined with standard induction chemotherapy. Sixty-three patients received PTK/ZK at doses of 500-1000 mg orally b.i.d. Safety and pharmacokinetic data were collected. Responses were evaluated according to standard bone marrow and peripheral blood criteria. At 1000 mg b.i.d., dose-limiting toxicities of lethargy, hypertension, nausea, emesis and anorexia were observed. Other adverse events related to PTK/ZK were dizziness, weakness, fatigue, diarrhea and pruritus; these were generally mild and reversible. Pharmacokinetic data showed that steady state was reached by day 14, there was no accumulation with repeat dosing and there was no significant increase in exposure at steady state beyond the maximum tolerated dose (MTD). Complete remission was observed in five of 17 AML patients treated with PTK/ZK combined with chemotherapy. In conclusion, the MTD of PTK/ZK is 750 mg orally b.i.d. The drug is generally well tolerated and can be given in combination with chemotherapy for patients with MDS and AML.
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PMID:Phase 1 study of PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor, for the treatment of acute myeloid leukemia and myelodysplastic syndrome. 1661 23

Background: Brain radiotherapy is the standard treatment option for multiple brain metastases (BMs) from non-small cell lung cancer (NSCLC), especially in the absence of a driver mutation. However, the prognosis for such patients remains poor. Apatinib is a potent antiangiogenic compound directed at the vascular endothelial growth factor receptor-2 (VEGFR-2); however, to date, there are no investigations of apatinib concurrent with brain radiotherapy for NSCLC patients with BMs. We report a case of EGFR wild-type and ALK-negative lung adenocarcinoma patient with multiple symptomatic BMs, who received apatinib together with brain radiation therapy. A favorable oncologic outcome was achieved for both brain metastatic lesions and the primary pulmonary tumor. Case Presentation: A 61-year-old female (never smoker) who initially presented with headache and dizziness was diagnosed with lung adenocarcinoma with multiple brain metastasis (cT2aN3M1b stage IV), and was negative for EGFR and ALK. The patient refused to receive chemotherapy and was only amenable to brain radiotherapy and targeted therapy. After approval from the institutional ethics committee, she underwent concurrent oral apatinib (500 mg/day) with whole brain radiation therapy (WBRT) (37.5Gy) with simultaneous in-field boost (49.5Gy) in 15 fractions with image guided intensity-modulated radiotherapy. Three weeks later, neurologic symptoms entirely ceased and a partial response (PR) for the BMs with near-complete resolution of peritumoral brain edema was achieved. Chest CT performed at the same time and showed shrinkage of the lung primary with a PR. The patient suffered grade III oral mucositis one week after brain radiotherapy and refused further apatinib. At 12 months after brain radiotherapy, the brain tumors remained well controlled. Conclusions: This is the first known documentation of a rapid clinical response of apatinib concurrent with brain radiotherapy in a lung adenocarcinoma patient with symptomatic multiple BMs. Apatinib combined with brain radiotherapy could be an alternative treatment option for BMs from NSCLC, especially for those without a driver mutation. Further clinical trials are required to corroborate this discovery.
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PMID:Clinical Response to Apatinib Combined With Brain Radiotherapy in EGFR Wild-Type and ALK-Negative Lung Adenocarcinoma With Multiple Brain Metastases. 3235 94