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We aimed to examine the use of circulating tumor cells (CTCs) as an effective measure of treatment efficacy and immune system function in metastatic breast cancer patients. CTCs are believed to be indicators of residual disease and thus pose an increased risk of metastasis and poorer outcomes to those patients who are CTC-positive. We obtained peripheral blood samples from 45 patients previously diagnosed with metastatic disease originating in the breast. Using TLR agonists that bind TLR ligands and upregulate immune effects versus unstimulated cells, we calculated a percent specific lysis using chromium-51 assay to illustrate the functional abilities of patient natural killer (NK) cells. We found those with greater than 5 CTCs per 7.5 mL blood had significantly decreased responses by their immune cells when compared with those patients who had 5 CTCs or less. We furthermore found a correlation between disease progression and CTC-positive patients, indicating that those who have a positive test should be closely monitored by their clinician. CTCs represent an exciting new clinical opportunity that will ideally utilize their low invasiveness and quick turnaround time to best benefit clinical scenarios.

Although significant advances have been made in the treatment of breast cancer using chemotherapy, less than half of the patients treated for localized breast cancer benefit from adjuvant chemotherapy and most patients with metastatic cancer eventually develop disease that is chemotherapy resistant. Targeted agents, such as inhibitors of tyrosine kinases, offer the opportunity to reverse chemotherapy resistance and enhance response in patients with localized and advanced breast cancer. Such combined approaches have been established for the treatment of advanced breast cancer and are now demonstrating benefit in the adjuvant arena. This review summarizes the results of several trials involving the use of tyrosine kinase inhibition in combination with chemotherapy for the treatment of breast cancer and discusses future directions for breast cancer biotherapy.

Breast cancer continues to be a major health problem despite a decrease in mortality rates over the past 2 decades. Although many advances have been made in the treatment of breast cancer, drug therapy for the disease continues to evolve as more is learned about cell biology and cellular signaling pathways. The development of targeted agents offers the hope of new therapies with better efficacy and tolerability. Biologic therapy has been a cornerstone of targeted therapy for the treatment of advanced breast cancer and is now entering the adjuvant arena. This review summarizes the results of several adjuvant studies and discusses future directions for breast cancer biotherapy.

3061 Background: We have studied our recent experience in the MDACC Clinical Translational Research Center (CTRC), the Phase I Program, and the Dept. of Thoracic/Head & Neck Medical Oncology to compare the extent of regulatory and other requirements for current phase I and II cancer clinical trials. Methods: We developed a comprehensive database, together with a Microsoft Excel spreadsheet matrix to analyze the number and extent of diagnostic and therapeutic requirements for each protocol. We then examined the demands for pharmacokinetic (PK) sampling as well as electrocardiography (ECG) in the first cycle of a protocol as a surrogate for study complexity. Results: Since October, 2002, 250 protocols have been conducted in the CTRC; 54.6% were Phase I clinical trials. We reviewed 65 trials, approximately one quarter of the total. Of these, 48 were phase I trials carried out by the Phase I Program. For comparison, we identified 17 phase II trials managed by the Dept. of Thoracic/Head & Neck Medical Oncology during the same time period. In the phase I trials there were significantly more PKs (mean ± SE = 16.69 ± 1.93) than in the phase II trials (mean ± SE = 1.82 ± 1.17) (p No significant financial relationships to disclose.

Purpose The development of new, targeted, less toxic agents is one of the highest priorities for progress in cancer treatment. Many of these new agents have fewer severe side effects but may require more detailed and subtle testing to assess biologic effects. Recent literature has focused on the cost and intensity of late phase II and III clinical trials, but little has been written about the requirements of current early-phase drug development. We are carrying out a study of our recent experience in the M.D. Anderson Cancer Center Clinical Translational Research Center (CTRC) and the Phase I Program to document the extent of regulatory and other requirements for current developmental cancer clinical trials. Methods We have developed an access database of virtually all studies, together with a Microsoft Excel spreadsheet matrix for each study that defines the number and extent of the diagnostic and therapeutic requirements for each protocol. RESULTS We initially analyzed demands for pharmacokinetic (PK) sampling in the first 4 weeks of a protocol as a representative marker for study complexity. Since October 2002, over 250 protocols have been conducted in the CTRC and the Phase I Program; 54.6% were phase I clinical trials. We picked a random sample of 67 trials, which is approximately a quarter of the total. Twenty-seven of these were phase I, 12 phase I/II, 24 later phase II, and four phase III trials. Our analysis demonstrates that in phase I trials, there was a median of 23 (range 1-58) PKs per patient. Phase I/II protocols had a median of 18.5 (range 8-53) PKs per patient. In contrast, later phase II studies had a median of 12 (range 1-51) samples per patient. Conclusions PK collection in phase I trials is complex and labor intensive and reflects just the tip of the iceberg, with increasingly complicated correlates and monitoring (electrocardiograms, physical examinations, and other tests). We will present an overview of this issue, as analyzed by our database. Successful and accurate phase I clinical trials will require resources and commitment for research infrastructure considerably greater than later-phase studies.