Phase I Study of Stealth Liposomal Doxorubicin in Combination With Gemcitabine in the Treatment of Patients With Metastatic Breast Cancer
| Autor: | E, Rivera, V, Valero, L, Syrewicz, Z, Rahman, F J, Esteva, R L, Theriault, M M, Rosales, D, Booser, J L, Murray, R C, Bast, G N, Hortobagyi, F L, Esteva |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Oncology Cancer Research medicine.medical_specialty Neutropenia Fever medicine.drug_class medicine.medical_treatment Phases of clinical research Breast Neoplasms Deoxycytidine Antimetabolite chemistry.chemical_compound Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Doxorubicin Aged Chemotherapy Dose-Response Relationship Drug business.industry Middle Aged medicine.disease Gemcitabine Metastatic breast cancer Surgery chemistry Liposomes Female business medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 19:1716-1722 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | PURPOSE: We conducted a single-institution phase I clinical trial to determine the maximum-tolerated dose (MTD) and define the toxic effects of stealth liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer. PATIENTS AND METHODS: Patients were eligible if they had disease progression with no limit on prior number of chemotherapy regimens. Prior treatment with liposomal doxorubicin and/or gemcitabine was not allowed. The starting dose of liposomal doxorubicin was 20 mg/m2 on day 1 only with a 20% dose escalation of the previous mg/m2 dose until MTD was reached. Gemcitabine was given as a fixed dose of 800 mg/m2 on days 1 and 8 every 3 weeks. RESULTS: We treated 27 patients of whom six had never received chemotherapy for their disease. Most had had visceral involvement as their dominant site of disease. The dose-limiting toxicity was myelosuppression, which included neutropenia and thrombocytopenia. However, neither neutropenic fever nor episodes of bleeding were major occurrences. Significant antitumor activity was also observed with a total of two complete and seven partial responses. The recommended phase II dose is liposomal doxorubicin 24 mg/m2 on day 1 and gemcitabine 800 mg/m2 on days 1 and 8 every 21 days. CONCLUSION: The combination of liposomal doxorubicin and gemcitabine is an active and well tolerated regimen when administered on a 21-day schedule. Myelosuppression limited further dose escalation, however, it did not increase the incidence of neutropenic fever. Significant antitumor activity seen in heavily and minimally pretreated patients warrants further evaluation of this combination. |
| Databáze: | OpenAIRE |
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