Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study.

Background: Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use.

Methods: This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 (n = 5), 1 (n = 26) or none (n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program.

Results: Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)).

Variability in lung cancer response to ALK inhibitors cannot be explained by the diversity of ALK fusion variants.

Multiple laboratory evidences indicate that distinct variants of ALK translocations differ in their biochemical properties and responsiveness to ALK tyrosine kinase inhibitors (TKIs). These data are supported by some clinical studies, which showed improved responses to crizotinib in non-small cell lung cancer (NSCLC) patients carrying particular variants of ALK translocation. We retrospectively considered 64 Russian patients with ALK-rearranged NSCLC, who were treated by crizotinib (n = 23), ceritinib (n = 39) or alectinib (n = 2).

[Antibodies to neuroleptics and their role in the mechanisms of the development of drug resistance in psychopharmacotherapy of patients with paranoid schizophrenia].

A study was made of the content of drug antibodies (DAT) to chlorpromazine, triphthazine and haloperidol in the blood sera of 112 patients with paranoid schizophrenia (acute period, curable exacerbation associated with the chronic course, and a group of therapeutically resistant subjects). Antibodies to neuroleptics were demonstrable in all the patients' groups. However, the rate of positive reactions and the content of DAT in the therapeutically resistant patients differed significantly from the characteristics in "acute" patients and in the group of "nonresistant" ones.