CYCLOPHOSPHANUM (Cyclophospha-num; synonym: Cyclophosphamidum,
Cyclophosphamide, Cytoxan, Endo-xan, Genoxal, Procytox, Sendoxan, Mitoxan, NSC-26271, B-518-ASTA;
joint venture. A) — antineoplastic means from group of the alkylating connections.] M '-bis-(r-Aether chloratus)-Р^ '-0-trimetilenovy ether of diamide of phosphoric acid:
White crystal powder, water soluble, easily alcohol-soluble, it is difficult — in isotonic solution of sodium chloride.
In the mechanism of action of C. reaction of alkylation is important (see), as a result a cut are damaged nucleinic to - you and proteins, including enzymes of tumor cells. In vitro Cyclophosphanum maloaktiven. In an organism it is activated by hl. obr. in a liver with release bis f-Aether chloratus) - amine. At intravenous administration the period of its semi-removal from blood makes 6g/2 hour. Drug is removed generally through kidneys.
202 CILIARY BODY
of C. it is effective at ovarian cancer (see), a mammary gland (see), small-celled cancer of a lung (see Lungs), a seminoma of a small egg (see the Seminoma), primary reticulosarcoma of a bone (see the Reticulosarcoma of a bone primary) and Ewing's sarcoma (see Ewing a tumor), an angiosarcoma (see), a lymphosarcoma (see), a lymphogranulomatosis (see), hron. a lymphoid leukosis (see Leukoses), a neuroblastoma (see) and Vilms's tumors at children (see Vilms a tumor), polycythemias (see), a multiple myeloma (see) and various paraproteinemias, in particular at Valdenstrem's disease (see Val-denstrem a disease), a makrofolliku-lyarny lymphoma (see the Lymphoma gigan-tofolltskulyarny), a lymphoma of Berkit-ta (see Berkitt a lymphoma). Unlike other alkylating drugs C. it is effective at acute leukoses at children and adults. Efficiency of C. at various malignant new growths fluctuates over a wide range depending on a form and degree of prevalence of process.
C. apply as one of the main components of the majority of combinations of antineoplastic means. Drug has immunodepressive property (see Yim mu but depressive substances).
Drug is used inside, entered intravenously, intramusculary, and also (at indications) inside-plevralno and intraperitoneally. Solutions are prepared just before the use: 0,2 g of Cyclophosphanum dissolve in 10 ml of sterile water for injections. Priment several modes: on 50 — 200 mg (1 — 3 mg/kg) inside daily; on 200 mg (3 mg/kg) daily or on 400 mg (6 mg/kg) every other day intravenously or intramusculary; on 1 g (15 mg/kg) intravenously
1 time in 5 days; on 2 — 3 g (30 — 45 mg/kg) intravenously 1 time in 2 — 3 weeks. In the course of treatment the modes of use of C. it is possible to change. E.g., after introduction of a high single dose (3 g or 45 mg/kg) in 2 weeks treatment can be continued on 1 g once in 5 days or on 400 mg every other day. Use of C. in high single doses (2 — 3 g or 30 — 45 mg/kg) allows to receive in some cases more expressed to lay down. effect, than its use in мень^ shy doses. One of the main advantages of use of high single doses is the possibility of rendering acute management by that patient, at to-rykh weight of a state is caused by a prelum of vitals the tumor sensitive to Cyclophosphanum. Duration of treatment and a total dose depend on portability of drug and its efficiency. Usually total dose on a course of treatment makes 6 — 14 g. In the absence of objective effect after introduction of 3 — 5 g of Cyclophosphanum its further use is considered inexpedient. After the termination of a basic course the maintenance therapy Cyclophosphanum on 0,1 — 0,2 g intravenously or intramusculary 2 times a week or on 0,05 — 0,1 g in 2 times a day can be appointed. During the use of C. as immuno depressive means it is appointed on 50 — 100 mg (1 — 1,5 mg/kg) inside daily (at good tolerance the daily dose is raised to 3 — 4 mg/kg). In the presence of metastasises of a tumor in serous covers of C. it is possible to enter inside-plevralno and intraperitoneally in a dose of 0,4 — 1 g as addition to system use of drug.
At treatment of C., especially at use of high single and total doses, by-effects can be observed. C. causes oppression of a leukopoiesis. At a sharp leukopenia transfuse blood or leukocyte weight, appoint stimulators of a hemopoiesis. Often there are nausea and vomiting. For reduction or prevention of vomiting appoint antiemetics (see). Toxic damage of a liver is noted extremely seldom. Sometimes the phenomena of aseptic hemorrhagic cystitis develop. One of frequent by-effects — a hair loss on the head. The hyperpegmentation of skin, cross striation of nails, dizziness, temporary deterioration in sight and hearing are sometimes observed. The listed by-effects, as a rule, have reversible character.
C. it is contraindicated at the expressed anemia, a leukopenia (less than 3000 leukocytes in 1 mkl to blood), a serious illness of a liver and kidneys, a cachexia.
Form of release: ampoules on 0,2 g of drug; tablets on 0,05 g, coated. Storage: in dry, cool (not higher than 10 °), the place protected from light.
See also Antineoplastic means.
Bibliography: And r and A. M. N and P e r e in about d-
h and to about in and N. I. Problems of modern chemotherapy of tumors, Vestn. USSR Academy of Medical Sciences, No. 12, page 55, 1982; e r sh and N island and p M. L. Complications at himio-and hormonal therapy of malignant tumors, M., 1982; Treatment of generalized forms of tumoral diseases, under the editorship of H. N. Blochina and Sh. Ekhardta, M., 1976; Transfer chikovan. I. Clinical chemotherapy of tumoral diseases, M., 1976; Chemotherapy of malignant tumors, under the editorship of H. N. Blochina, M., 1977; Atkins H.L., Gregg H. G. and. N at m a n G. A. Clinical apprai-sal of cyclophosphamide in malignant neoplasms, Cancer, v. 15, p. 1076, 1962;
S e 1 1 e i C., E with k h a r d t S. N e-m e t h L. Chemotherapy of neoplastic diseases, Budapest, 1970. BB. H. Falcons.