romurtide and Neoplasms

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Anti-Bacterial Agents; Bacterial Infections; Cytokines; Drug Synergism; Hematopoiesis; Humans; Infections; Leukopenia; Mice; Mycoses; Neoplasms; Virus Diseases

We have reported that the bacterial cell-wall skeletons, such as mycobacteria, nocardia, corynebacteria, propionibacteria and listeria, had potent adjuvant activity on immune responses. It was reported that N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) was the minimum structural requirement of adjuvant activity of the bacterial cell-wall skeleton and a variety of MDP derivatives and related compounds were synthesized. Among the synthetic MDP derivatives, we have selected MDP-Lys(L18)(romurtide) as the immunostimulant, by using experimental models for non-specific host resistance against Escherichia coli in mice. Romurtide was shown to have host-stimulating activity against bacterial, fungal and viral infections, cytokine producing activity and the capacity to increase the number of leukocytes and platelets in experimental models. It was also shown that the clinical effectiveness of romurtide on the restoration of the number of leukocytes and platelets of cancer patients treated with chemotherapy or radiation therapy. The mechanism of action of romurtide is discussed.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Cytokines; Hematopoiesis; Humans; Infections; Leukopenia; Mice; Neoplasms

The most appropriate time for administration was studied based on examination of the total number of leukocytes, differential white blood count, and the number of platelets in 30 cases in which 200 micrograms Romurtide (Nopia) was injected subcutaneously on the day of radiotherapy, 5 times a week, for 2 weeks, totally 10 times because leukopenia was caused during treatment with radiotherapy. It was recognized that the number of leukocytes, mainly neutrophils, increased from 1 week after starting administration of Romurtide to after the completion of administration (2 weeks after administration), except 1 week after completion of administration. The increasing effect in the number of platelets was not recognized, and it had decreased from at the completion of administration to 1 week after the completion of administration of Romurtide. The rate of completion of radiotherapy was 100% without any serious adverse events, but there were 4 cases in which fever was observed. Therefore, it is not very favorable to administer Romurtide immediately after radiation, taking account of the treatment period of radiotherapy. It is also considered that it would be necessary to start radiation after sufficient recovery of the number of leukocytes or increase in their number by using G-CSF preparation in cases in which the leukocyte count has fallen since starting radiation due to the influence of the preceding chemotherapy.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Adult; Aged; Aged, 80 and over; Drug Administration Schedule; Female; Humans; Leukocyte Count; Leukopenia; Male; Middle Aged; Neoplasms; Time Factors

The effectiveness of thrice-weekly injection of Romurutide for leukocytopenia due to radiation therapy was analyzed. Twenty-two patients were randomly divided into two groups. Ten of group A cases were injected 3 times per week 10 times (3 weeks) and 12 of group B cases were injected 5 times per week 10 times (2 weeks). White blood cell counts and neutrophil numbers in group A were almost the same as in group B at day-3 and day-8, and those in group A were more than in group B at day-15 and day-22, although there were no statistical significances. Lymphocyte percentages, monocyte percentages and platelet cell counts between groups showed no differences. Injections were stopped in 3 cases due to fever (2 in group A, 1 in group B). The effects were recognized in nineteen cases (excluding above 3 cases). The effect of this thrice-weekly injection method during the injection period was the same or more than with 5 injections/week, and the period of the former was 50% longer. The 3 weekly injection method is more effective for prophylaxis of leukocytopenia.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Breast Neoplasms; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasms; Uterine Cervical Neoplasms

Muramyl dipeptide (MDP) and its synthetic derivatives which comes from the major constituent of bacterial cell wall has various biological activities as host defence mechanisms. One of the synthetic MDP derivatives, MDP-Lys (L 18), muroctasin has potent biological activities with less adverse reactions among various MDP derivatives. Muroctasin has proved to be safe to use clinically as the results of phase I clinical study. We attempted to evaluate its clinical usefulness and safety from the view point of restorative activity in leukopenia that was induced by cancer chemotherapy in patients with malignancies. It is concluded that muroctasin is effective as well as useful on the restorative activities against leukopenia in lung cancer patients after cancer chemotherapy, with the optimal daily dosage of 200 micrograms for six times by subcutaneous injections through phase II and phase III clinical cooperative studies in Japan. Supposed mode of action of muroctasin for granulocytosis may be the results of CSF production due to stimulation of macrophage by muroctasin. This first clinical success of restoration of leukopenia in patients with cancer receiving cancer chemotherapy by MDP derivative, muroctasin, might be not only advantageous for cancer chemotherapy and/or radiation therapy but also for preventing infections occurring in compromised host due to neutropenia in cancer patients by means of cytotoxic cancer chemotherapy or irradication.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Antineoplastic Agents; Humans; Leukopenia; Neoplasms

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adult; Aged; Female; Humans; Leukopenia; Male; Middle Aged; Neoplasms; Radiotherapy