Activity of JM9 in advanced ovarian cancer: a phase I-II trial. 1985

V H Bramwell, and D Crowther, and S O'Malley, and R Swindell, and R Johnson, and E H Cooper, and N Thatcher, and A Howell

Thirty-nine patients with advanced solid tumors, including 28 with ovarian cancer, were entered in a phase I-II trial of a new platinum analog, JM9. Twenty-three patients had received prior chemotherapy which did not include cisplatin. Based on preliminary information from an ongoing study, our starting dose was 180 mg/m2. The total dose of JM9 was administered in 1 L of saline infused over 1 hour, with no additional hydration or electrolyte supplementation. Courses were repeated at 3-week intervals or after full recovery from thrombocytopenia. One hundred thirty-nine courses (range, one to six per patient) were administered at four dose levels: 180 mg/m2 (13 courses); 240 mg/m2 (64 courses); 300 mg/m2 (45 courses); and 350 mg/m2 (17 courses). The dose-limiting toxic effect was thrombocytopenia, which was dose-related and cumulative. Median platelet count nadirs were 50, 47, 25, and 28 X 10(9)/L for previously treated patients at dose levels of 180, 240, 300, and 350 mg/m2, respectively. For patients who had not received prior chemotherapy, the corresponding values were 403, 61, 44, and 36 X 10(9)/L. The nadir was predictable at Day 14 with recovery by Day 21 in earlier courses, but with delay of recovery to Days 28-42 in later courses and at higher dose levels. Twenty-five courses of chemotherapy in 15 patients were associated with a platelet count nadir of less than 20 X 10(9)/L, but despite this, serious hemorrhage was rare. Leukopenia was dose-related and mild; the median wbc count (X 10(9)/L) was 2.2 (range, 1.0-7.3) at the highest dose level of 350 mg/m2. The leukocyte count nadir was later than that for the platelet count (Days 21-28), and recovery was often not complete by the time of retreatment. All patients showed a progressive rise in mean corpuscular volume in successive courses, often accompanied by a fall in hemoglobin. Transfusions were required in 14 patients, 12 of whom had received prior chemotherapy. Nausea and vomiting, starting within 1 hour of drug administration, occurred in all patients, but appeared to be less severe and prolonged compared to that occurring with cisplatin. Diarrhea occurred in most patients at the two higher dose levels. There was no evidence of significant renal impairment, electrolyte disturbance, hearing loss, or peripheral neuropathy. Two patients had mild allergic reactions shortly after drug infusion and two others developed vasculitic rashes which were self-limiting.(ABSTRACT TRUNCATED AT 400 WORDS)

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
D009944 Organoplatinum Compounds Organic compounds which contain platinum as an integral part of the molecule. Compounds, Organoplatinum
D010051 Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS. Cancer of Ovary,Ovarian Cancer,Cancer of the Ovary,Neoplasms, Ovarian,Ovary Cancer,Ovary Neoplasms,Cancer, Ovarian,Cancer, Ovary,Cancers, Ovarian,Cancers, Ovary,Neoplasm, Ovarian,Neoplasm, Ovary,Neoplasms, Ovary,Ovarian Cancers,Ovarian Neoplasm,Ovary Cancers,Ovary Neoplasm
D010976 Platelet Count The number of PLATELETS per unit volume in a sample of venous BLOOD. Blood Platelet Count,Blood Platelet Number,Platelet Number,Blood Platelet Counts,Blood Platelet Numbers,Count, Blood Platelet,Count, Platelet,Counts, Blood Platelet,Counts, Platelet,Number, Blood Platelet,Number, Platelet,Numbers, Blood Platelet,Numbers, Platelet,Platelet Count, Blood,Platelet Counts,Platelet Counts, Blood,Platelet Number, Blood,Platelet Numbers,Platelet Numbers, Blood
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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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