Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients
| Autor: | H Nakashima, Carmen J. Allegra, Nancy Harold, Ronald Lieberman, Chris H. Takimoto, Frank Grollman, Michael D. Liang, J M Hamilton, William L. Dahut, Jean L. Grem, W. Corse, Susan G. Arbuck, M Sorensen, Alice P. Chen |
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| Rok vydání: | 1996 |
| Předmět: |
Adult
Male Cancer Research Neutropenia Nausea medicine.medical_treatment Antineoplastic Agents Drug Administration Schedule Pharmacokinetics Neoplasms Granulocyte Colony-Stimulating Factor Medicine Humans Infusions Intravenous Aged Chemotherapy biology business.industry Topoisomerase Middle Aged medicine.disease Treatment Outcome Oncology Anesthesia biology.protein Vomiting Camptothecin Female Aminocamptothecin medicine.symptom business Perfusion |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 14(4) |
| ISSN: | 0732-183X |
| Popis: | PURPOSE To conduct a phase I and pharmacologic study of the new topoisomerase I inhibitor, 9-aminocamptothecin (9-AC). PATIENTS AND MATERIALS A 72-hour infusion of 9-AC was administered every 14 days to 48 solid-tumor patients at doses of 5 to 59 microg/m2/h without granulocyte colony-stimulating factor (G-CSF) and 47 to 74 microg/m2/h with G-CSF. RESULTS Without G-CSF, two of eight patients who received 47 microg/m2/h had dose-limiting neutropenia in their initial cycle, as did both patients who received 59 microg/m2/h (with a platelet count < 25,000/microL in one). With G-CSF, zero of seven patients treated with 47 microg/m2/h had dose-limiting neutropenia in their first cycle, while dose-limiting neutropenia occurred in six of 14 patients (with platelet count < 25,000/microL in five) entered at 59 microg/m2/h. Among 39 patients entered at > or = 25 microg/m2/h 9-AC with or without G-CSF, fatigue, diarrhea, and nausea/vomiting of grade 2 severity ultimately occurred in 54%, 30%, and 38%, respectively, while grade 3 toxicities of each type occurred in 8% of patients. Steady-state 9-AC lactone concentration (Css) increased linearly from 0.89 to 10.6 nmol/L, and correlated strongly with leukopenia ( r = .85). CONCLUSION The recommended phase II dose of 9-AC given by 72-hour infusion every 2 weeks is 35 microg/m2/h without G-CSF or 47 microg/m2/h with G-CSF support. Dose escalation in individual patients may be possible according to their tolerance. |
| Databáze: | OpenAIRE |
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