stilbenes and Thrombocytopenia

Preclinical evidence of synergy led to a phase I trial employing combretastatin A-4 phosphate (CA4P), a novel tubulin-binding antivascular drug, in combination with carboplatin.. Based on preclinical scheduling studies, patients were treated on day 1 of a 21-day cycle. Carboplatin was given as a 30-minute i.v. infusion and CA4P was given 60 minutes later as a 10-minute infusion.. Sixteen patients with solid tumors received 40 cycles of therapy at CA4P doses of 27 and 36 mg/m(2) together with carboplatin at area under the concentration-time curve (AUC) values of 4 and 5 mg min/mL. The dose-limiting toxicity of thrombocytopenia halted the dose escalation phase of the study. Four patients were treated at an amended dose level of CA4P of 36 mg/m(2) and carboplatin AUC of 4 mg min/mL although grade 3 neutropenia and thrombocytopenia were still observed. Three lines of evidence are adduced to suggest that a pharmacokinetic interaction between the drugs results in greater thrombocytopenia than anticipated: the carboplatin exposure (as AUC) was greater than predicted; the platelet nadirs were lower than predicted; and the deviation of the carboplatin exposure from predicted was proportional to the AUC of CA4, the active metabolite of CA4P. Patient benefit included six patients with stable disease lasting at least four cycles.. This study of CA4P and carboplatin given in combination showed dose-limiting thrombocytopenia. Pharmacokinetic/pharmacodynamic modeling permitted the inference that altered carboplatin pharmacokinetics caused the increment in platelet toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Carboplatin; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Nausea; Neoplasms; Neutropenia; Stilbenes; Thrombocytopenia; Treatment Outcome; Vomiting

Topics: Adult; Antioxidants; Female; Humans; Melanosis; Neurocutaneous Syndromes; Platelet Count; Resveratrol; Stilbenes; Thrombocytopenia

Within a period of four years 35 patients with metastatic breast cancer were treated with tamoxifen. One third had objective remissions, average duration of complete remission being 30.6 months and of partial remission 13.7 months. Mean survival time from start of tamoxifen treatment in five patients with complete remission was 30.6 months while in seven with partial remission it was 20.4 months. Nine patients with unresponsive metastases had a mean survival time of 24.3 months, the remaining 14 patients who deteriorated surviving for 11.7 months. Ten of the 12 patients who responded well were over 60 years old. Lymph-node and lung or pleural metastases were significantly reduced by treatment in four of eight and six of 15 cases, respectively. Satisfactory regression of bony metastases was never seen. Because of this, combined tamoxifen (10 mg twice daily) and methandrostenolone (1 mg twice daily) was given to an additional five patients, with one of them responding. Side effects included thrombocytopenia and hypercalcaemia.

Topics: Adult; Age Factors; Bone Neoplasms; Breast Neoplasms; Female; Humans; Hypercalcemia; Lung Neoplasms; Lymphatic Metastasis; Methandrostenolone; Middle Aged; Neoplasm Metastasis; Pleural Neoplasms; Remission, Spontaneous; Stilbenes; Tamoxifen; Thrombocytopenia; Time Factors