Phase I and II Study of Exisulind in Combination With Capecitabine in Patients With Metastatic Breast Cancer
| Autor: | Francisco J. Esteva, Terry L. Smith, W. Fraser Symmans, Edgardo Rivera, Gabriel N. Hortobagyi, W. Joseph Thompson, Lajos Pusztai, James L. Murray, Kimberly M. Nealy, Vicente Valero, Jim Hou Zhen, Banu Arun, Daniel J. Booser, Amy Gibbs, Clark M. Whitehead |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Adult
Oncology Antimetabolites Antineoplastic Cancer Research medicine.medical_specialty Anthracycline medicine.medical_treatment Breast Neoplasms Deoxycytidine Capecitabine chemistry.chemical_compound Sulindac 3' 5'-Cyclic-GMP Phosphodiesterases Exisulind Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Prodrugs Neoplasm Metastasis Adverse effect Aged Cyclic Nucleotide Phosphodiesterases Type 5 Chemotherapy Taxane Phosphoric Diester Hydrolases business.industry Middle Aged medicine.disease Cyclic Nucleotide Phosphodiesterases Type 2 Immunohistochemistry Metastatic breast cancer Surgery chemistry Concomitant Female Fluorouracil business medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 21:3454-3461 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2003.02.114 |
| Popis: | Purpose: We studied the safety and clinical activity of exisulind in combination with capecitabine in 35 patients with metastatic breast cancer (MBC). Patients and Methods: All patients had received previous anthracycline and taxane chemotherapies. Two dose levels of exisulind were explored, 125 and 250 mg orally bid as continuous daily therapy, concomitant with capecitabine 2,000 mg/m2 for 14 days in 21-day cycles. In the phase I study, the dose-limiting toxicities were hand-foot syndrome and diarrhea. The 125-mg bid dose was selected for phase II testing. Results: The most common nonhematologic grade 2 to 3 adverse events were hand-foot syndrome (57%) and fatigue (48%). The most frequent grade 2 to 3 laboratory abnormality was granulocytopenia. No death, unexpected adverse events, or cumulative toxicity were encountered. One complete and four partial responses were achieved (objective response rate, 16%) in the 31 patients assessable for response. The median duration of response was 31 weeks; three patients experienced stable disease longer than 26 weeks. Overall clinical benefit (complete response, partial response, or stable disease > 26 weeks) was 23%. Fourteen specimens were available for immunohistochemical assessment of phosphodiesterase-5 isoenzyme (PDE-5) and PDE-2 expression, which are the targets of exisulind. Eighty percent of tumors showed some expression of PDE-5 in the invasive cancer cells including 35% that showed moderate or strong staining. PDE-2 showed moderate or strong staining in 78% of tumors. There was no apparent association between tumor response and staining intensity. Conclusion: Exisulind (125 mg orally bid) in combination with capecitabine is well tolerated and the combination has anticancer activity similar to that of capecitabine alone in heavily pretreated patients with MBC. |
| Databáze: | OpenAIRE |
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