Phase II trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma
| Autor: | Ian Quirt, Reinhard Lohmann, Elizabeth Eisenhauer, Wendy Walsh, Richard Tozer, Susan Burdette-Radoux, Nancy Wainman, A. Dimitrios Colevas, D. Scott Ernst |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Diarrhea Male medicine.medical_specialty Maximum Tolerated Dose Vomiting Nausea medicine.medical_treatment Antineoplastic Agents Anorexia Gastroenterology Piperidines Internal medicine medicine Humans Pharmacology (medical) Neoplasm Metastasis Infusions Intravenous Melanoma Fatigue Aged Flavonoids Pharmacology business.industry Immunotherapy Middle Aged medicine.disease Cyclin-Dependent Kinases Surgery Regimen Treatment Outcome Oncology Toxicity Female medicine.symptom business Adjuvant |
| Zdroj: | Investigational New Drugs. 22:315-322 |
| ISSN: | 1573-0646 0167-6997 |
| Popis: | Purpose: To test the activity of the cyclin dependent kinase (cdk) inhibitor flavopiridol in malignant melanoma, a disease with frequent abnormalities of the cyclin dependent kinase system. Patients and methods: Patients had histologically proven, unidimensionally measurable malignant melanoma, incurable by standard therapy. Prior adjuvant immunotherapy was allowed, but patients were otherwise untreated for advanced disease. Flavopiridol was administered at a dose of 50 mg/m2 IV over 1 hour daily × 3 days every 3 weeks. Patients were assessed for response every 2 cycles. Results: 17 patients were accrued over 5 months. No objective responses were documented in the 16 patients evaluable for response. Seven patients (44%) had stable disease after 2 cycles, with a median of 2.8 months (range 1.8–9.2). The most common treatment-related non-hematologic toxicities were diarrhea (82%), nausea (47%), fatigue (41%), anorexia (35%) and vomiting (29%). Most treatment-related toxicities were mild, except for diarrhea (grade 3 in 3 patients, grade 4 in 1 patient), nausea (grade 3 in 1 patient) and tumor pain (grade 3 in 1 patient). Hematologic toxicities were minimal, none worse than grade 2. Eighty-eight percent of patients received ≥90% planned dose intensity; 2 patients had dose reductions for gastrointestinal (GI) toxicity. Conclusions: Flavopiridol is well tolerated at the dose regimen used in this study, with an acceptable (primarily GI) toxicity profile. Although 7 of the 16 patients had stable disease ranging from 1.8 to 9.2 months in duration, there was no evidence of significant clinical activity in malignant melanoma by objective response criteria. |
| Databáze: | OpenAIRE |
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