Seminars in oncology
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Seminars in oncology · Oct 1999
Multicenter Study Clinical TrialCHOP plus rituximab chemoimmunotherapy of indolent B-cell lymphoma.
Indolent (low-grade) B-cell lymphomas are responsive to single-agent and combination chemotherapy agents, but unfortunately possess an incurable, relapsing nature. Novel agents and innovative treatment approaches need to be evaluated in these patients, with the ultimate goals of maintaining good quality of life and prolonging overall survival. Novel combinations of chemotherapeutic agents, monoclonal antibodies (both unlabeled and radiolabeled), and anti-idiotypic vaccine therapies are currently being evaluated. ⋯ A 95% overall response (55%, complete remission; 40%, partial remission) rate using strict definitions for complete remission and extensive staging studies was achieved in a 40-patient intent-to-treat group. In addition, seven of seven patients with follicular histologies achieving complete remission also had clearing of BCL-2 (chromosome 14;18 translocation) positivity from blood and marrow by sensitive polymerase chain reaction assay, suggesting the eradication of subclinical minimal residual disease. Based on its single-agent efficacy, excellent toxicity profile, and ability to be successfully combined with combination chemotherapy (ie, CHOP), rituximab is currently undergoing extensive investigation in a large number of worldwide clinical trials to determine its optimal use in the treatment of CD20-positive neoplasms.
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Seminars in oncology · Aug 1999
ReviewNonclinical studies addressing the mechanism of action of trastuzumab (Herceptin).
HER2 is a ligand-less member of the human epidermal growth factor receptor or ErbB family of tyrosine kinases. In normal biological systems, HER2 functions as a co-receptor for a multitude of epidermal growth factor-like ligands that bind and activate other HER family members. HER2 overexpression is observed in a number of human adenocarcinomas and results in constitutive HER2 activation. ⋯ Trastuzumab treatment of mouse xenograft models results in marked suppression of tumor growth. When given in combination with standard cytotoxic chemotherapeutic agents, trastuzumab treatment generally results in statistically superior antitumor efficacy compared with either agent given alone. Taken together, these studies suggest that the mechanism of action of trastuzumab includes antagonizing the constitutive growth-signaling properties of the HER2 system, enlisting immune cells to attack and kill the tumor target, and augmenting chemotherapy-induced cytotoxicity.
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Seminars in oncology · Aug 1999
Clinical TrialPhase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer.
The HER2/neu proto-oncogene is overexpressed in 25% to 30% of patients with breast cancer. Trastuzumab (Herceptin; Genentech, San Francisco, CA), a recombinant humanized monoclonal antibody with high affinity for the HER2 protein, inhibits the growth of breast cancer cells overexpressing HER2. In this phase II study the efficacy and toxicity of weekly administration of trastuzumab was evaluated in 46 patients with metastatic breast cancer whose tumors overexpressed HER2. ⋯ Minor responses (seen in 2 patients) and stable disease (14 patients) lasted for a median of 5.1 months. These results demonstrate that trastuzumab is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers who have received extensive prior therapy. The regression of human cancer through the targeting of putative growth factor receptors such as HER2 warrants further evaluation of trastuzumab in the treatment of breast cancer.
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Seminars in oncology · Aug 1999
Clinical Trial Controlled Clinical TrialHealth-related quality of life in women with metastatic breast cancer treated with trastuzumab (Herceptin).
The measurement of health-related quality of life (HRQL) was an important component of clinical trials of trastuzumab (Herceptin; Genentech, San Francisco, CA) in women with progressive HER2-overexpressing metastatic breast cancer who may or may not have had prior chemotherapy. Health-related quality of life was measured at baseline and specified intervals during therapy using the European Organization for Research and Treatment of Cancer core Quality of Life Questionnaire (QLQ-C30, version 1.0). Five domains were chosen a priori for analysis: global quality of life, physical, role and social functioning, and fatigue. ⋯ However, comparison of on-treatment scores with baseline in patients receiving chemotherapy alone indicated mild worsening of physical and role functioning and of fatigue throughout the duration of treatment, whereas a similar comparison of those receiving chemotherapy with trastuzumab revealed mild worsening of role functioning at weeks 8 and 20 and of fatigue only at week 8. These results suggest that trastuzumab may be associated with an amelioration of the deleterious effects of chemotherapy alone. In summary, in the doses and schedules used in these studies, trastuzumab is not associated with worsening of HRQL.