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Phase I trial of liposomal doxorubicin and ZD1839 in patients with refractory gynecological malignancies or metastatic breast cancer
- Source :
- International journal of clinical oncology. 15(4)
- Publication Year :
- 2009
-
Abstract
- Pegylated liposomal doxorubicin has activity in both breast and ovarian cancer. Preclinical data noted that ZD1839 acts synergistically with chemotherapy. Given the lack of cross-resistance between these two agents, a phase I trial was initiated examining the safety and efficacy of the combination of liposomal doxorubicin and ZD1839 in patients with recurrent gynecologic or metastatic breast cancer. Dose-limiting toxicity (DLT) was defined within the first two cycles of treatment. Escalating doses of liposomal doxorubicin were administered every 4 weeks with ZD1839. Pharmacokinetic analysis and correlative studies were performed. Thirty-five patients were enrolled in this study: six in each cohort. One DLT (febrile neutropenia) was observed in cohort 2. Dose level 3 was determined to be the maximum tolerated dose (MTD), and an additional ten patients were accrued. Serious adverse events (SAEs) included one patient with mental status changes believed secondary to disease progression and two central nervous system (CNS) bleeds believed to be unrelated to the combination of study agents. Toxicities were generally mild except for skin and gastrointestinal toxicity. No cardiac toxicity was observed. The best response to therapy included four partial responses and 20 patients with stable disease. Liposomal doxorubicin with ZD1839 is an active regimen but is associated with increased skin toxicity in patients with advanced breast and gynecologic cancer.
- Subjects :
- Oncology
Adult
medicine.medical_specialty
Time Factors
Maximum Tolerated Dose
Genital Neoplasms, Female
medicine.medical_treatment
Breast Neoplasms
Breast cancer
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Adverse effect
Aged
Neoplasm Staging
Aged, 80 and over
Salvage Therapy
Chemotherapy
business.industry
Gefitinib
Hematology
General Medicine
Middle Aged
medicine.disease
Metastatic breast cancer
Regimen
Treatment Outcome
Doxorubicin
Drug Resistance, Neoplasm
Toxicity
Quinazolines
Surgery
Female
Ovarian cancer
business
Febrile neutropenia
Boston
Subjects
Details
- ISSN :
- 14377772
- Volume :
- 15
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- International journal of clinical oncology
- Accession number :
- edsair.doi.dedup.....17f049a15f0ade0f2a5444d2843e33c2