Concern over decreased training in embryology and developmental/reproductive toxicology.
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Biology↗
Biomedical subjects
Gary Kimmel
Publications and source records attributed to Gary Kimmel.
Phase II study of trastuzumab plus gemcitabine in chemotherapy-pretreated patients with metastatic breast cancer.
We evaluated the efficacy and toxicity of trastuzumab plus gemcitabine in patients with HER2-positive metastatic breast cancer (MBC). Sixty-four patients were enrolled, the majority of whom (95%) had been treated with an anthracycline and a taxane before study enrollment. Eligible women were treated with gemcitabine (1200 mg/m(2) weekly for 2 weeks with the third week off on a 21-day cycle) plus weekly doses of trastuzumab (4-mg/kg loading dose; 2 mg/kg thereafter) until disease progression. The median patient age was 55 years, and the median number of previously administered (including adjuvant) chemotherapy regimens was 3. Twenty-two patients were scored as 2+ for HER2 expression by immunohistochemistry; 39 patients scored 3+. Three patients were assessed as HER2-negative on central pathology review and were ineligible for evaluation. Fifty-nine of the 61 patients remained evaluable for response. The objective response rates were 38% in the intent-to-treat population (23 of 61) and 44% among the 39 patients with HER2 3+ expression. The median response duration was 5.8 months, median overall survival was 14.7 months, and median time to disease progression was 5.8 months. Trastuzumab plus gemcitabine was well tolerated. No cases of clinical congestive heart failure occurred. Grade 3/4 toxicities included asthenia in 4 patients, fever in 4, neutropenia in 18, dyspnea in 6, abdominal or back pain in 3, and edema and nausea in 1 patient each. The combination of trastuzumab plus gemcitabine appears to be well tolerated and effective for patients with HER2-positive MBC previously treated with chemotherapy.
Adult↗
Risk assessment.
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Abnormalities, Drug-Induced↗
Phase II trial of gemcitabine plus trastuzumab in metastatic breast cancer patients previously treated with chemotherapy: preliminary results.
Preliminary results of a phase II study of gemcitabine plus trastuzumab in previously treated (up to 3 previous regimens) metastatic breast cancer patients are presented. Patients had histologically confirmed metastatic breast cancer, with 2+ or 3+ tumor HER2 expression. Treatment consisted of gemcitabine 1200 mg/m2 over 30 minutes intravenously on days 1 and 8 every 21 days, and trastuzumab 4 mg/kg over 90 minutes, followed by 2 mg/kg infused over 30 minutes weekly. Treatment was continued until disease progression or unacceptable toxicity occurred. Preliminary results are available on the first 38 patients enrolled. Median patient age was 53 years, 53% had estrogen receptor/progesterone receptor-positive disease, and HER2 staining was 2+ in 39% and 3+ in 61% of patients. There was a median of 3 previously administered (including adjuvant) chemotherapy regimens, and a median of 4.5 treatment cycles per patient has been administered so far. Twelve patients (32%) have had an objective partial response, with a median response duration of 8.6 months. Median time to disease progression is 6.7 months to date, with a median overall survival of 10.2 months. No unexpected toxicities or grade 4 nonhematologic toxicities have been observed; 2 patients developed grade 4 neutropenia and 1 patient had febrile neutropenia. Thus, gemcitabine/ trastuzumab resulted in an encouraging 32% response rate, given the heavily pretreated patient population. Tolerability was good overall, with no unexpected side effects observed.
Antibodies, Monoclonal↗
Overview: Using mode of action and life stage information to evaluate the human relevance of animal toxicity data.
A complete mode of action human relevance analysis--as distinct from mode of action (MOA) analysis alone--depends on robust information on the animal MOA, as well as systematic comparison of the animal data with corresponding information from humans. In November 2003, the International Life Sciences Institute's Risk Science Institute (ILSI RSI) published a 2-year study using animal and human MOA information to generate a four-part Human Relevance Framework (HRF) for systematic and transparent analysis of MOA data and information. Based mainly on non-DNA-reactive carcinogens, the HRF features a "concordance" analysis of MOA information from both animal and human sources, with a focus on determining the appropriate role for each MOA data set in human risk assessment. With MOA information increasingly available for risk assessment purposes, this article illustrates the further applicability of the HRF for reproductive, developmental, neurologic, and renal endpoints, as well as cancer. Based on qualitative and quantitative MOA considerations, the MOA/human relevance analysis also contributes to identifying data needs and issues essential for the dose-response and exposure assessment steps in the overall risk assessment.
Aging↗