The discovery of anaplastic lymphoma kinase (ALK) tyrosine kinase gene rearrangement mutations in non-small cell lung cancer (NSCLC) has driven continuous advancements in ALK-targeted therapies. The next generation of ALK tyrosine kinase inhibitor, Brigatinib, has demonstrated significant efficacy in patients with ALK-positive NSCLC, offering clinical benefits in deep response of tumor, treatment of brain metastases patients, quality of life, and long-term survival. This review will provide current advancements and exploratory directions for Brigatinib.
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Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Lung Neoplasms/enzymology* ; Pyrimidines/therapeutic use* ; Organophosphorus Compounds/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVETo investigate the efficacy of 153Sm-EDTMP in the treatment of bone metastasis of prostate cancer (PCa) by comparison with zoledronic acid.

METHODSWe assigned 55 PCa patients with bone metastasis to receive 153Sm-EDTMP (n = 31) and zoledronic acid (n = 24), the former injected intravenously at the dose of 37.0 MBq/kg body weight, and the latter administered by slow intravenous drip at 4 mg in 100 ml of 0.9% sodium chloride. We performed 99mTc-MDP bone scan before and 1 -2 months after the treatment.

RESULTSThe rate of pain relief was 83.9% in the 153Sm-EDTMP group and 58.3% in the zoledronic acid group (P = 0.035), and that of bone metabolism change was 64.5% in the former and 33.3% in the latter (P = 0.022).

CONCLUSION153Sm-EDTMP is an ideal agent for the treatment of prostate cancer with bone metastasis.

Aged ; Aged, 80 and over ; Bone Neoplasms ; drug therapy ; secondary ; Diphosphonates ; therapeutic use ; Humans ; Imidazoles ; therapeutic use ; Male ; Middle Aged ; Neoplasm Metastasis ; drug therapy ; Organometallic Compounds ; therapeutic use ; Organophosphorus Compounds ; therapeutic use ; Prostatic Neoplasms ; drug therapy ; pathology

Vascular disrupting agents (VDAs) have presented a new kind of anti-cancer drug in recent years. VDAs take advantage of the weakness of established tumor endothelial cells and their supporting structures. In contrast to anti-angiogenic therapy, which inhibits the outgrowth of new blood vessels, vascular targeting treatments selectively attack the existing tumor vasculature. Here we summarized the anti-tumor activities, mechanisms and clinical applications of small molecule VDAs.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; therapeutic use ; Animals ; Antineoplastic Agents ; chemistry ; pharmacology ; therapeutic use ; Bibenzyls ; chemistry ; pharmacology ; therapeutic use ; Diphosphates ; chemistry ; pharmacology ; therapeutic use ; Endothelial Cells ; drug effects ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; pathology ; Neovascularization, Pathologic ; Oligopeptides ; chemistry ; pharmacology ; therapeutic use ; Organophosphorus Compounds ; chemistry ; pharmacology ; therapeutic use ; Serine ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Stilbenes ; chemistry ; pharmacology ; therapeutic use ; Tubulin Modulators ; chemistry ; pharmacology ; therapeutic use ; Xanthones ; chemistry ; pharmacology ; therapeutic use

Adolescent ; Adult ; Atropine ; therapeutic use ; Female ; Foodborne Diseases ; drug therapy ; Humans ; Insecticides ; poisoning ; Male ; Muscarinic Antagonists ; therapeutic use ; Organophosphorus Compounds ; Pesticide Residues ; poisoning ; Pesticides ; poisoning ; Treatment Outcome

Adult ; Atropine ; therapeutic use ; Bronchodilator Agents ; therapeutic use ; Combined Modality Therapy ; Female ; Hemofiltration ; Humans ; Insecticides ; poisoning ; Male ; Middle Aged ; Organophosphorus Compounds ; Poisoning ; therapy ; Treatment Outcome

OBJECTIVEA certain fraction of patients failed palliative treatment of 153Sm- ethylenediaminetetramethy lenephosphate (153Sm-EDTMP) for painful skeletal metastases were reviewd. A comparative analysis was designed to identify the factors related to therapeutic response.

METHODSFrom a 3-year multi-center clinical trial, 51 cases were collected who did not respond to an intravenous injection of 153Sm-EDTMP at a dosage of 0.5-1.5 mCi/kg. The therapeutic efficacy was evaluated via changes of symptoms, general condition, consumption of analgesics, sum of effect product, and Karnofsky scores. The age, sex, history of treatment, tumor type, location of bony involvement, uptake ratio and number of metastases, and doses used by the patients were compared to those of the responders.

RESULTSIn 51 non-responders, 43 were male, 34 suffered from lung cancer, 41 had bone lesions in the vertebrae, 39 in the pelvis, and 24 had metastases in the lower extremities. Sex distribution, tumor type and location of the lesion differed significantly between responders and non-responders. No other factor showed differences between the two groups. Though patients of younger age, and lesions with lower uptake of radiopharmaceutical seemed to fail the treatment more easily as observed clinically, this was not confirmed by statistical analysis.

CONCLUSIONThe sex of the patients, certain types of primary tumors and metastases to lower parts of the body were found to influence the patients' response to a single dose of 153Sm-EDTMP palliation. Further exploration of a better way to determine dosage and predict response for each individual case is needed.

Adult ; Aged ; Aged, 80 and over ; Analgesics, Non-Narcotic ; therapeutic use ; Bone Neoplasms ; physiopathology ; radiotherapy ; secondary ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Organometallic Compounds ; therapeutic use ; Organophosphorus Compounds ; therapeutic use ; Palliative Care

OBJECTIVETo evaluate the measurement of Samarium-153 ethylenediaminetetramethylene phosphonic acid ((153)Sm-EDTMP) bone uptake rate using whole-body scintigraphy and analyze the relationship between bone uptake rate and therapeutic effect.

METHODSSixty-six patients with painful bony metastases from prostate (n = 15), lung (n = 20), breast (n= 18), nasopharyngeal carcinoma (NPC) (n=5), colon (n=2), kidney (n=2) and unknown cause (n=4) carcinoma were examined with whole-body scintigraphy 10 min and 5 h post administration of (153)Sm-EDTMP. Bone uptake rate was then calculated. (1 ) Complete response (CR): disappearance of > 2 metastases, Karnofsky Performance Score (KPS) increase > 20, moderate or complete remission of bone pain 7 d post injection of (153)Sm-EDTMP. (2) Partial response (PR): disappearance of 1-2 metastases, KPS increase 10-20, moderate remission of bone pain in 3 wk. (3) Non-response (NR): no disappearance or shrinkage of metastases, KPS increase < 10, no or slight remission of bone pain.

RESULTSThe range of bone uptake rate in 66 patients was 31 .9% - 86.6% (mean = 56. 0%). The bone uptake rate in the CR group (17 cases, 25.7%), PR group (24 cases, 36.4%), and NR group (25 cases, 37.9%) was 52.4% - 86.6% (mean = 68.7%), 43.7% - 70.4% (mean = 58.3%), and 31.9%- 51 .5% (mean = 41 . 0%) respectively. Statistical analysis showed that there was a significant difference between the CR and PR groups ( t = 4.258, P = 0.001 ) as well as between PR and NR groups ( t = 8.48,P = 0.001 ).

CONCLUSIONSUsing a simple and reliable whole-body scintigraphic technique to calculate prospectively the bone uptake rate, we have, for the first time in China, reported the relationship between bone uptake rate and therapeutic effect. This allows nuclear medicine physicians to calculate a safe and effective dose of (153)Sm-EDTMPin individual patients to palliate bone cancer pain without myelotoxicity.

Bone Neoplasms ; drug therapy ; secondary ; Bone and Bones ; metabolism ; Female ; Humans ; Male ; Organometallic Compounds ; pharmacokinetics ; therapeutic use ; Organophosphorus Compounds ; pharmacokinetics ; therapeutic use