A multicentre phase II trial of bryostatin-1 in patients with advanced renal cancer
| Autor: | Andrew Protheroe, David Propper, Barry W. Hancock, Cheng Han, Srinivasan Madhusudan, Frances R. Balkwill, Adrian L. Harris, Helena M. Earl, Paul A. Vasey, Pippa Corrie, A Turner, S F Hoare |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
myalgia
Adult Male Cancer Research medicine.medical_specialty Bryostatin 1 medicine.medical_treatment Antineoplastic Agents Gastroenterology Clinical Lactones Internal medicine Medicine Humans phase II trial Infusions Intravenous Carcinoma Renal Cell Aged Chemotherapy business.industry Interleukin-6 Cancer kidney cancer Middle Aged medicine.disease Bryostatins Nephrectomy bryostatin-1 Kidney Neoplasms Endocrinology Treatment Outcome Oncology Female Hormone therapy Macrolides medicine.symptom business Kidney cancer Kidney disease protein kinase C |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Protein kinase C (PKC) has a critical role in several signal transduction pathways, and is involved in renal cancer pathogenesis. Bryostatin-1 modulates PKC activity and has antitumour effects in preclinical studies. We conducted a multicentre phase II clinical trial in patients with advanced renal cancer to determine the response rate, immunomodulatory activity and toxicity of bryostatin-1 given as a continuous 24 h infusion weekly for 3 out of 4 weeks at a dose of 25 mug m(-2). In all, 16 patients were recruited (11 males and five females). The median age was 59 years (range 44-68). Patients had been treated previously with nephrectomy (8) and/or interferon therapy (9) and/or hormone therapy (4) and/or radiotherapy (6). Eight, five and three patients had performance statuses of 0, 1 and 2, respectively. A total of 181 infusions were administered with a median of 12 infusions per patient (range 1-29). Disease response was evaluable in 13 patients. Three patients achieved stable disease lasting for 10.5, 8 and 5.5 months, respectively. No complete responses or partial responses were seen. Myalgia, fatigue, nausea, headache, vomiting, anorexia, anaemia and lymphopenia were the commonly reported side effects. Assessment of biological activity of bryostatin-1 was carried out using the whole-blood cytokine release assay in six patients, two of whom had a rise in IL-6 levels 24 h after initiating bryostatin-1 therapy compared to pretreatment values. However, the IL-6 level was found to be significantly lower at day 28 compared to the pretreatment level in all six patients analysed. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|