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author:("oraz, Ruth")
1.  Phase I Study of Bryostatin 1, a Protein Kinase C Modulator, Preceding Cisplatin in Patients with Refractory Non-hematologic Tumors 
Purpose
Preclinical data suggested that bryostatin-1 (bryo) could potentiate the cytotoxicity of cisplatin when given prior to this drug. We designed a phase I study to achieve tolerable doses and schedules of bryo and cisplatin in combination and in this sequence.
Methods
Patients with non-hematologic malignancies received bryo followed by cisplatin in several schedules. Bryo was given as an 1 hour and a 24 hour continuous infusion, while cisplatin was always given over 1 hour at 50mg/m2 and 75mg/m2; the combined regimen was repeated on an every 3-week and later on an every 2-week schedule. Bryo doses were escalated until recommended phase II doses were defined for each schedule. Patients were evaluated with computerized tomography every 2 cycles.
Results
53 patients were entered. In an every 2-week schedule, the 1 hour infusion of bryo became limited by myalgia that was clearly cumulative. With cisplatin 50 mg/m2 its recommended phase II dose was 30 mcg/m2. In the 3-week schedule, dose-limiting toxicities were mostly related to cisplatin effects while myalgias were tolerable. Pharmacokinetics unfortunately proved to be unreliable due to bryo’s erratic extraction. Consistent inhibition of PKC isoform eta (η) in peripheral blood mononuclear cells was observed following bryo.
Conclusions
Bryo can be safely administered with cisplatin with minimal toxicity;, however, only 4 patients achieved an objective response. Modulation of cisplatin cytotoxicity by bryo awaits further insight into the molecular pathways involved.
doi:10.1007/s00280-009-0931-y
PMCID: PMC3901370  PMID: 19221754
2.  Impact of a Commercial Reference Laboratory Test Recurrence Score on Decision Making in Early-Stage Breast Cancer 
Journal of Oncology Practice  2007;3(4):182-186.
Purpose
To investigate whether recurrence score (RS) as determined using a commercial reference laboratory test influences clinicians' treatment recommendations and eventual treatment in patients with early-stage breast cancer.
Methods
A retrospective analysis was performed on 74 patients from a community-based oncology practice with estrogen receptor (ER) –positive, lymph node (LN) –negative stage I or II breast cancer for which RS was obtained. Demographic and pathology information was extracted from medical records. Ten-year relapse-free survival was calculated using Adjuvant! Online. Treatment recommendations before the RS knowledge were compared with treatment recommendations after RS knowledge and to the treatment eventually administered.
Results and Conclusion
A weak correlation was found between RS and both patient age and tumor size, modest correlation between RS and tumor grade, and modest correlation between RS and 10-year recurrence as determined by Adjuvant! Online. For 21% and 25% of patients, knowledge of the RS changed the clinicians' treatment recommendations and eventual treatment, respectively. The decision to change from hormone therapy to chemotherapy (with or without hormone therapy) was generally associated with high RS (high distant recurrence risk as determined by the commercial reference laboratory test), whereas the decision to change from chemotherapy to hormone therapy was generally associated with low RS (low distant recurrence risk as determined by the commercial reference laboratory test). Knowledge of the RS changed treatment recommendations and eventual treatment in patients with ER-positive/LN-negative early-stage breast cancer. Use of genomic-based prognosis may result in more accurate estimates of true recurrence risk than currently possible with commonly used prognostic factors (such as patient age, tumor size, and tumor grade) alone and thus lead to an increase in appropriate adjuvant therapy decision making.
doi:10.1200/JOP.0742001
PMCID: PMC2793805  PMID: 20859407

Results 1-2 (2)