Phase I trial of homoharringtonine administered by prolonged continuous infusion. 1986

J A Neidhart, and D C Young, and E Kraut, and B Howinstein, and E N Metz

Cephalotaxine alkaloids have been extensively used in the Peoples Republic of China for treatment of acute leukemias and solid tumors (Yu-hua, L., Shu-fen, G., Fu-ying, Z., Shu-zhi, X., and Hui-lin, Z. Chin. Med. J., 96: 303-305, 1983). Several Phase I trials of homoharringtonine have been completed in the United States using either bolus administration or continuous infusion over a 5-day period. The major toxicities have been hypotension following rapid administration and myelosuppression when lower doses are infused over 5 to 7 days. None of these studies, however, reproduce the schedule used in China which is i.v. infusion of approximately 1 mg/day over 4-8 h for a period of 14-28 days or more, followed by a rest period of approximately 7-14 days. This study more closely reproduces that schedule as a Phase I trial by decreasing the daily dose of homoharringtonine and using a continuous infusion schedule to allow escalation of total days of treatment. Forty-eight patients entered the study. The final recommended dose of homoharringtonine is 1 mg/m2/day for 30 days followed by a 2-week rest period. The dose limiting toxicity of myelosuppression was severe and prolonged in some patients. Nonhematological toxicities were minimal and generally well tolerated. Patients should be followed with at least weekly blood counts and treatment interrupted pending full marrow recovery if the granulocyte count falls below 1,000/mm3 or the platelet count falls below 100,000/mm3.

UI MeSH Term Description Entries
D007263 Infusions, Parenteral The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping. Intra-Abdominal Infusions,Intraperitoneal Infusions,Parenteral Infusions,Peritoneal Infusions,Infusion, Intra-Abdominal,Infusion, Intraperitoneal,Infusion, Parenteral,Infusion, Peritoneal,Infusions, Intra-Abdominal,Infusions, Intraperitoneal,Infusions, Peritoneal,Intra Abdominal Infusions,Intra-Abdominal Infusion,Intraperitoneal Infusion,Parenteral Infusion,Peritoneal Infusion
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D004341 Drug Evaluation Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. Evaluation Studies, Drug,Drug Evaluation Studies,Drug Evaluation Study,Drug Evaluations,Evaluation Study, Drug,Evaluation, Drug,Evaluations, Drug,Studies, Drug Evaluation,Study, Drug Evaluation
D005260 Female Females
D006248 Harringtonines Tetracyclic spiro-BENZAZEPINES isolated from the seeds of CEPHALOTAXUS. They are esters of the alkaloid cephalotaxine and may be effective as antineoplastic agents. Cephalotaxine Alkaloids,Cephalotaxus Alkaloids,Alkaloids, Cephalotaxine,Alkaloids, Cephalotaxus
D006410 Hematopoiesis The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY). Hematopoiesis, Medullary,Haematopoiesis,Medullary Hematopoiesis
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077863 Homoharringtonine Semisynthetic derivative of harringtonine that acts as a protein synthesis inhibitor and induces APOPTOSIS in tumor cells. It is used in the treatment of MYELOID LEUKEMIA, CHRONIC. Ceflatonin,Cephalotaxine,Homoharringtonine (3(R))-isomer,Omacetaxine,Omacetaxine Mepesuccinate,Synribo

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