Vincristine with dactinomycin

A variety of other agents with cytotoxic effects has been used to suppress the immune system. These drugs include chlorambucil (Leukeran), dactinomycin (Cosmegen), mercaptopurine (Purinethol), vinblastine (Velban), and vincristine (Oncovin, Vincasar).41 These... 

Therapeutic applications Dactinomycin is used in combination with surgery and vincristine (see p. 390) for the treatment of Wilm s tumor. With methotrexate (see p. 378) it is effective in the treatment of gestational choriocarcinoma. Some soft-tissue sarcomas also respond. 

Of 17 adult men who had been treated before puberty for sarcoma with high-dose pulse cyclophosphamide (median dose 20.5 m/m ) as part of regimens containing vincristine, dactinomycin, and cyclophosphamide, with or without doxorubicin, 10 had azoospermia, five had oligospermia, and only two had normal sperm counts (34). The authors concluded that a previous suggestion that puberty acts as a protection to infertihty was not borne out and that the risk of infertihty was proportional to the cumulative dose of cyclophosphamide. 

Green DM, Finklestein JZ, Norkool P, D Angio GJ. Severe hepatic toxicity after treatment with single-dose dactinomycin and vincristine. A report of the National Wilms Tumor Study. Cancer 1988 62(2) 270-3. 

Dactinomycin is used against ihabdomyasarcoma and Wilms tumor in children. It can be liicsaving for women with choriocarcinoma resistant to methotrexate. In combination with vincristine and cyclophosphamide, it has received some use in. solid tumors in children. Toxic reaction.s include anorexia, nausea, and vomiting. Bone marrow depression, resulting in pancytopenia, may occur within a week after therapy. Alopecia, erythema, and tissue injury may ixtcur at the injection site. 

Clinically important, potentially hazardous interactions with altretamine, amikacin, aminoglycosides, antineoplastics, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, corticosteroids, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin, estramustine, etoposide, fludarabine, fluorouracil, gemcitabine, gentamicin, hydroxyurea, idarubicin, ifosfamide, indomethacin, kanamycin, levamisole, lomustine, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, mitoxantrone, neomycin, pentostatin, plicamycin, procarbazine, streptomycin, streptozocin, thioguanine, thiotepa, tobramycin, tretinoin, uracil, vinblastine, vincristine, vinorelbine... 

Dactinomycin is an antineoplastic agent that is the principal component of the mixture of actinomycins produced by Streptomyces parvullus. It inhibits messenger RNA synthesis. Dactinomycin (0.5 mg/day IV for 5 days), in combination with vincristine, radiotherapy, and surgery, is used in Wilms tumor in conjunction with vincristine, cyclophosphamide, and doxorubicin, it is used in choriocarcinoma in combination with methotrexate, it is used in testicular carcinoma and in combination with cyclophosphamide and radiotherapy, it is used in Ewing s sarcoma. Dactinomycin inhibits messenger RNA synthesis by anchoring to a purine-pyrimidine (DNA) base pair by intercalation (see Figure 15). The toxicity of dactinomycin increases when combined with radiation therapy. 

The most important clinical use of dactinomycin is in the treatment of rhabdomyosarcoma and Wilms tumor in children, where it is curative in combination with primary surgery, radiotherapy, and other drugs, particularly vincristine and cyclophosphamide. Antineoplastic activity has been noted in Ewing s tumor, Kaposi s sarcoma, and soft-tissue sarcomas. Dactinomycin can be effective in women with advanced cases of choriocarcinoma in combination with methotrexate. Dactinomycin also has been used as an immunosuppressant in renal transplants. 

Items 80-81. A patient with metastatic choriocarcinoma was ti eated first with methotrexate plus dactinomycin and subsequently with a combination of cisplatin and vincristine. In both regimens, drug dosage was maximized to a toxicity limit of a 2-log decrease in blood platelets. The effects of chemotherapy were monitored by urinary chorionic gonadotropin (UCG, U/24 h), as shown in the data below. 

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