mitopodozide and Neoplasms

Pre-clinical studies indicate that cisplatin encapsulated in STEALTH((R))liposomes (SPI-77) retains anti-tumour activity, but has a much reduced toxicity, compared to native cisplatin. A phase I study was conducted to determine the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m(-2)by intravenous infusion every 4 weeks. Blood samples taken during, and up to 3 weeks after, administration and plasma and ultrafiltrate were prepared immediately. Urine was collected, when possible, for 3 days after administration. SPI-77 administration was well tolerated with the major toxicity being an infusion reaction which responded to modification of the initial infusion rate of SPI-77. Limited haematological toxicity and no nephrotoxicity were observed. No responses to treatment were seen during the course of this phase I study. Measurement of total plasma platinum showed that cisplatin was retained in the circulation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable doses of cisplatin. Comparison of plasma and whole blood indicated that cisplatin was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administered over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies are required to address the issue of reformulation of liposomally bound cisplatin.

Topics: Adolescent; Antineoplastic Agents; Area Under Curve; Child; Child, Preschool; Cholesterol; Cisplatin; Dose-Response Relationship, Drug; Female; Humans; Infant; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Liposomes; Male; Neoplasms; Podophyllin; Podophyllotoxin; Time Factors; Triglycerides

The cancer risk was studied by comparison of 305 rheumatoid arthritis (RA) patients exposed to Proresid during a mean time of 22 months and 305 RA patients exposed to sodium aurothiomalate during a mean time of 19 months with the regional cancer register. The mean observation time was 6.9 years (2,117 person-years) for the Proresid-treated and 7.5 years (2,293 person-years) for the gold-treated patients. No increased risk of total malignancies was observed for either group. However, looking at separate tumours, an increased risk of lymphoma and leukemia was found although only significant in the gold-treated group. It was not correlated to dosage or duration of either therapy. The increased risk is consistent with earlier reports of an increased risk of hematopoietic malignancies in RA patients. Marginal over and underreporting, particularly of hematopoietic malignancies, were observed, mainly due to clinicians' failure to report and to recall false reports.

Topics: Antineoplastic Agents; Arthritis, Rheumatoid; Cohort Studies; Female; Gold Sodium Thiomalate; Humans; Infusions, Parenteral; Male; Morbidity; Neoplasms; Podophyllin; Podophyllotoxin; Risk Factors; Sweden

Proresid, mainly consisting of podophyllotoxin derivatives and two glycosides thereof, has been used as a disease-modifying antirheumatic drug in Sweden since the late 1960s. A life-table analysis of Proresid treatment averaging 41 months (range 4-144) in 79 rheumatoid arthritis patients showed a termination rate of 40, 56, 75 and 85% after 1/2, 1, 2 and 4 years, respectively. Dominant reasons for discontinuing therapy were inefficacy (37%) and gastrointestinal symptoms (35%). The risk of discontinuation of therapy due to inefficacy was constant over time, while the risk due to other causes, including side effects, gradually decreased. A comparison with injectable gold therapy showed, after adjusting for confounding factors, that the total termination incidence was higher (p < 0.05) in the Proresid-treated patients. A comparison with the regional cancer register of 334 patients exposed to Proresid for a mean time of 2.2 years showed no increased cancer risk after a mean observation time of 6.1 years.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Cohort Studies; Female; Gold; Humans; Incidence; Injections; Life Tables; Male; Middle Aged; Neoplasms; Patient Compliance; Patient Dropouts; Podophyllin; Podophyllotoxin; Prognosis; Risk Factors; Treatment Outcome

Topics: Aged; Amyloidosis; Arthritis; Diarrhea; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Neoplasms; Podophyllin; Podophyllotoxin

Topics: Female; Humans; Hydrazines; Male; Neoplasms; Podophyllin; Podophyllotoxin; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms

Topics: Antineoplastic Agents; Biomedical Research; Drug Therapy; Hydrazines; Injections, Intra-Arterial; Neoplasms; Podophyllotoxin; Podophyllum; Toxicology