zithromax and Lymphoma--B-Cell--Marginal-Zone

In view of the antineoplastic effects of the macrolide clarithromycin in mucosa associated lymphatic tissue (MALT)-lymphoma, we performed a pilot study assessing levels of azithromycin in plasma, peripheral blood mononuclear cells (PBMC) and polymorphonuclear leukocytes (PMN) of MALT-lymphoma patients to determine the pharmacokinetics and potential influences of respective concentrations on the therapeutic outcome. In total 16 patients with MALT-lymphoma received 1.5 g of oral azithromycin once-weekly over 6 months. Blood was sampled directly prior to the following dose every 4 weeks during treatment. Drug levels were analysed by high performance liquid chromatography in plasma and intracellularly in PBMC and PMN. They were correlated with patients' age, weight and body-mass-index and compared between patients responsive or unresponsive to treatment. Mean azithromycin plasma levels of all patients were 58.97 ± 30.48 ng/ml, remaining stable throughout the treatment period. Correlation analysis of plasma azithromycin showed no significance. Intracellular PBMC concentrations were 6648 ± 8479 ng/ml, without any significant difference between responders and non-responders. Mean PMN levels were 39,274 ± 25,659 ng/ml and significantly higher in patients unresponsive to treatment (t = 2.858, p = 0.017). Our drug regime led to continuously high plasma and exceedingly high intracellular concentrations of azithromycin in PBMC and PMN. Age, weight or body-mass-index had no significant influence on plasma levels and thence should not be considered in dosage finding. High AZM levels in PBMC did not lead to a better treatment response, whereas enrichment in PMN suggested a poorer outcome. The threshold for immunomodulatory effects on lymphoma cells might not have been reached. Additionally, the finding of stable plasma and intracellular concentrations over months with high-dose azithromycin administered in intervals might also be important for the further design of azithromycin-based trials against MALT-lymphoma.Trial registration: EudraCT 2016-001521-13, 14/06/2016.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Female; Humans; Leukocytes, Mononuclear; Lymphoma, B-Cell, Marginal Zone; Male; Middle Aged

The macrolide clarithromycin has been reported as active for therapy of mucosa associated lymphoid tissue (MALT) lymphoma. Pharmacokinetic properties, however, require continuous daily intake over a prolonged period of time. As the macrolide azithromycin is characterized by a long half-life as well as potential antineoplastic activity in vitro, we have performed a phase II trial of long-term once-weekly oral azithromycin for treatment of MALT lymphoma. In a 2-stage-design, 16 patients (10 f/6 m) with histologically verified and measurable MALT lymphoma were included in the first phase of the trial, which could be expanded to a maximum of 46 patients depending on remissions in the first phase. Patients were given oral azithromycin 1500 mg once-weekly 4 times a month, and restaging was performed after 3 and 6 months. Two patients had gastric and 14 extragastric MALT lymphoma; 12/16 patients were treatment-naive and received azithromycin as first line treatment. Tolerance of this regimen was excellent, and 14/16 patients received 6 months of treatment as scheduled, while 1 patient each discontinued after 4 (progressive disease) and 1 cycle (personal reasons), respectively. The most commonly observed side effects were mild nausea (n = 8) and diarrhea (n = 4). Efficacy, however, was low as only 4/16 patients (25%) responded, with 2 complete and 2 partial remissions, 9 patients (56%) had stable disease, and 3 patients 19%) were rated as progressive disease. As the predefined activity of more than 7/16 patients responding was not reached, the study was stopped after 16 patients. Although long-term once-weekly oral azithromycin showed some antilymphoma activity, the response rate was below the predefined threshold of interest. However, based on our data, one cannot rule out suboptimal dosing in our study; attempts to study azithromycin at a different mode of application might be warranted in the future.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Agents; Azithromycin; Drug Administration Schedule; Female; Humans; Lymphoma, B-Cell, Marginal Zone; Male; Middle Aged; Retreatment; Treatment Outcome

In February 2007, a 13-year old boy presented with a livid tumour in the lower conjunctival fornix of the left eye. OPHTHALMOLOGICAL FINDINGS: The tumor was salmon-coloured, bulging and elastic and filled the whole lower conjunctival fornix of the left eye. There was no other pathological finding in the left eye. Uncorrected visual acuity was 20/20. Intraocular pressure was 12 mmHg. The eye was fully motile.. Incisional biopsy was performed in February 2007. The tumor was histologically an extranodal MALT lymphoma. DNA testing for Chlamydophila trachomatis and Chlamydophila pneumonia was negative. Systemic treatment was started with doxycycline (200 mg daily). After six weeks, the tumour was slightly smaller. Azithromycin 500 mg once a week was added. 18 months after initiation of the treatment, the tumour had completely regressed. A second sample taking in the former tumor area showed tumor-free conjunctiva and subconjunctival tissue. As a precaution, the combined antibiotic therapy was continued for 10 months and the patient was followed for five more years. The lymphoma did not relapse in the conjunctiva and orbit or in the whole body.. We showed that extranodal MALT lymphomas of the conjunctiva can be successfully treated with antibiotics alone. At the start of therapy, the child was 13 years old. To our knowledge, this patient is the first child in Germany and one of the first in the world with ocular adnexal lymphoma who could be successfully treated with combined antibiotic therapy and who could be followed up for 5 years without relapse. Thus, we could avoid radiotherapy or chemotherapy in childhood and eliminate the risk of a therapy-induced secondary malignancy.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Conjunctival Neoplasms; Doxycycline; Drug Therapy, Combination; Follow-Up Studies; Humans; Longitudinal Studies; Lymphoma, B-Cell, Marginal Zone; Male; Recurrence; Treatment Outcome

Helicobacter pylori infection is highly prevalent and may cause disease in 10% to 15% of infected individuals: duodenal and gastric ulcer, gastric cancer and gastric lymphoma. Guidelines for a test-and-treat policy have been published by the European H. pylori working group in Maastricht.. To assess the current approach to H. pylori-related diseases, indications for testing and eradication therapy, among internists and surgeons of a University affiliated medical center.. A 15-items questionnaire was formulated according to the Maastricht II test-and-treat recommendation and distributed among the physicians of 6 internal medicine departments and the department of surgery. The questionnaires were completed anonymously at the department's staff meeting, under the supervision of the head of the department. All questions required a yes/no answer; the maximum possible score was 15. The relative ratio (RR) of correct answers was calculated for every question and by subgroups as follows: all participants, internists, surgeons, experts and residents in internal medicine and surgery.. The response rate was 68% (55 out of 80 physicians). Total score for all participants was 10.9 (RR = 0.73), significantly lower than the maximum score of 15 (RR = 1.00). The internists had significantly higher average score than the surgeons for 2 questions: causative agent in gastric cancer (p = 0.003) or gastric lymphoma (p = 0.003), 1 question about triple therapy, PPI, penicillin and azythromycin being not recommended (p = 0.022), and for 1 question of test-and-treat policy: should this strategy apply to family members of gastric cancer patients (p = 0.045). Only 56% of the internists and 21% of surgeons knew what MALToma is, and the correlation with H. pylori infection.. Knowledge of Surgeons and Internists regarding infection and correlation with diseases or test and treat policy should be improved.

Topics: Academic Medical Centers; Anti-Bacterial Agents; Azithromycin; Data Collection; Drug Therapy, Combination; Gastritis; General Surgery; Guideline Adherence; Health Knowledge, Attitudes, Practice; Helicobacter Infections; Helicobacter pylori; Humans; Internship and Residency; Israel; Lymphoma, B-Cell, Marginal Zone; Penicillins; Peptic Ulcer; Practice Guidelines as Topic; Referral and Consultation; Stomach Neoplasms