scholarly journals Targeting Solid Tumors With BTK Inhibitors

Author(s):  
Fatih M. Uckun ◽  
Taracad Venkatachalam

The repurposing of FDA-approved Bruton’s tyrosine kinase (BTK) inhibitors as therapeutic agents for solid tumors may offer renewed hope for chemotherapy-resistant cancer patients. Here we review the emerging evidence regarding the clinical potential of BTK inhibitors in solid tumor therapy. The use of BTK inhibitors may through lead optimization and translational research lead to the development of new and effective combination regimens for metastatic and/or therapy-refractory solid tumor patients.

Author(s):  
Jonathan M. Hyak ◽  
Mayar Al Mohajer ◽  
Daniel M. Musher ◽  
Benjamin L. Musher

Abstract Objective: To investigate the relationship between the systemic inflammatory response syndrome (SIRS), early antibiotic use, and bacteremia in solid-tumor patients. Design, setting, and participants: We conducted a retrospective observational study of adults with solid tumors admitted to a tertiary-care hospital through the emergency department over a 2-year period. Patients with neutropenic fever, organ transplant, trauma, or cardiopulmonary arrest were excluded. Methods: Rates of SIRS, bacteremia, and early antibiotics (initiation within 8 hours of presentation) were compared using the χ2 and Student t tests. Binomial regression and receiver operator curves were analyzed to assess predictors of bacteremia and early antibiotics. Results: Early antibiotics were administered in 507 (37%) of 1,344 SIRS-positive cases and 492 (22%) of 2,236 SIRS-negative cases (P < .0001). Of SIRS-positive cases, 70% had blood cultures drawn within 48 hours and 19% were positive; among SIRS negative cases, 35% had cultures and 13% were positive (19% vs 13%; P = .003). Bacteremic cases were more often SIRS positive than nonbacteremic cases (60% vs 50%; P =.003), but they received early antibiotics at similar rates (50% vs 49%, P = .72). Three SIRS components predicted early antibiotics: temperature (OR, 1.7; 95% CI, 1.31–2.29; P = .0001), tachycardia (OR, 1.4; 95% CI, 1.10–1.69; P < .0001), and white blood-cell count (OR, 1.8; 95% CI, 1.56–2.14; P < .0001). Only temperature (OR, 1.6; 95% CI, 1.09–2.41; P = .01) and tachycardia (OR, 1.5; 95% CI, 1.09–2.06; P = .01) predicted bacteremia. SIRS criteria as a composite were poorly predictive of bacteremia (AUC, 0.57). Conclusions: SIRS criteria are frequently used to determine the need for early antibiotics, but they are poor predictors of bacteremia in solid-tumor patients. More reliable models are needed to guide judicious use of antibiotics in this population.


2006 ◽  
Vol 12 (12) ◽  
pp. 3782-3791 ◽  
Author(s):  
Larry J. Schaaf ◽  
Lisa A. Hammond ◽  
Stuart J. Tipping ◽  
Richard M. Goldberg ◽  
Rakesh Goel ◽  
...  

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8548-8548
Author(s):  
P. Jiang ◽  
M. Choi ◽  
D. Smith ◽  
L. Heilbrun ◽  
S. M. Gadgeel

8548 Background: The percentage of cancer patients ≥ 80 years old is expected to rise in the United States. However data are limited on use of chemotherapy in this group of patients. Methods: Retrospective identification of patients who received systemic chemotherapy at our cancer center between 1/1/2000 to 12/31/2004 was performed using the computer generated pharmacy data and medical records. Patients who had diagnosis of cancer and ≥ 80 years were included in the study; patients receiving only supportive care, hormonal therapy, or oral chemotherapy were excluded. The protocol for this study was approved by the Wayne State University IRB. Results: A total of 133 patients ≥ 80 years who received chemotherapy was analyzed. The median age was 83 and 31% of the patients were ≥ 85 years. There were more females (61%) than males (39%). The gender distribution was more even (47% v. 53%) after excluding gender specific tumors. The racial distribution was diverse- Whites 65 (49%); Blacks 41 (31%); Other 18 (13%); Unknown 9 (7%). 16% of the patients had hematologic malignancy and 84% had solid tumors. Gynecological cancers (32%) followed by aerodigestive cancers (26%) were the most common solid tumors. Solid tumor patients primarily had regional (48%) or distant (45%) disease. During the first regimen, 512 cycles of chemotherapy was delivered with a median of 3 cycles per patient (range 1–24 cycles); 40% of patients received only 2 cycles of chemotherapy. 64% of patients were able to receive chemotherapy without 2nd cycle delay. The distribution of single or multidrug regimens was fairly similar; Solid tumors 52% v. 48%; Hematologic cancers 43% v. 57%. Carboplatin and paclitaxel (22%) was the most common regimen among solid tumor patients. 26% of all patients received a second regimen. The 1 year survival rates among hematologic cancer and solid tumor patients were 65% and 48%, respectively. Stage of disease was the only statistically significant factor predicting survival. Conclusions: In this diverse group of cancer patients ≥ 80 years old and selected for chemotherapy, the treatment was feasible. The survival outcomes in this elderly population were comparable to those of a younger patient population suggesting that the treatment is beneficial. No significant financial relationships to disclose.


2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e14501-e14501 ◽  
Author(s):  
Jeeyun Lee ◽  
Seung Kim ◽  
Sujin Lee ◽  
Se Hoon Park ◽  
Joon Oh Park ◽  
...  

1979 ◽  
Vol 300 (6) ◽  
pp. 289-291 ◽  
Author(s):  
Lawrence H. Einhorn ◽  
Stephen D. Williams

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