Phase I and pharmacologic study of intermittent twice-daily oral therapy with capecitabine in patients with advanced and/or metastatic cancer
| Autor: | Stan B. Kaye, A. S. T. Planting, David Allman, Melanie Mackean, Osterwalder B, Bruno Reigner, T Griffin, Chris Twelves, Jan H.M. Schellens, Jaap Verweij |
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| Přispěvatelé: | Medical Oncology |
| Rok vydání: | 1998 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Abdominal pain medicine.medical_treatment Administration Oral Antineoplastic Agents Deoxycytidine Gastroenterology Drug Administration Schedule Metastasis Capecitabine SDG 3 - Good Health and Well-being Oral administration Neoplasms Internal medicine medicine Humans Aged Chemotherapy Leukopenia Dose-Response Relationship Drug business.industry Cancer Middle Aged medicine.disease Oncology Fluorouracil Anesthesia Female medicine.symptom business medicine.drug |
| Zdroj: | Journal of Clinical Oncology, 16(9), 2977-2985. American Society of Clinical Oncology |
| ISSN: | 1527-7755 0732-183X |
| Popis: | PURPOSE Capecitabine is an orally administered fluoropyrimidine carbamate selectively activated to fluorouracil (5-FU) in tumors. It passes through the intestinal mucosal membrane intact and is subsequently activated by a cascade of three enzymes that results in the preferential release of 5-FU at the tumor site. PATIENTS AND METHODS In this phase I study, capecitabine was administered twice daily as outpatient therapy, each cycle administered for 2 weeks followed by 1 week of rest. Thirty-four patients with solid tumors, all of whom except three patients were pretreated, were treated at dose levels from 502 to 3,514 mg/m2 daily. RESULTS The median treatment duration was four cycles (85 days; range, 14 to 833+ days). Two patients continue on treatment at 686 and 833+ days. Capecitabine 3,000 mg/m2 daily was not tolerable, with dose-limiting toxicities of diarrhea with hypotension, abdominal pain, and leukopenia. Palmar-plantar erythrodysesthesia (PPE) became evident at higher dose levels after prolonged treatment. Evidence of objective tumor response was reported in four patients at 2,510 mg/m2 daily and greater (one complete response [CR] and three partial responses [PRs]) with subjective minor tumor responses in a further seven patients. Pharmacokinetic studies showed rapid gastrointestinal absorption of capecitabine, followed by extensive conversion into 5'-deoxy-5-fluorouridine (5'-DFUR), with only low systemic 5-FU levels. CONCLUSION Capecitabine is a tolerable oral outpatient therapy that shows promising clinical activity in a variety of cancers. The recommended phase II dose is 2,510 mg/m2 daily administered by this intermittent schedule. |
| Databáze: | OpenAIRE |
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