Publications
Department of Medicine faculty members published more than 3,600 peer-reviewed articles in 2024.
2018
2018
2018
BACKGROUND
Androgen deprivation therapy plus docetaxel (D-ADT) increases overall survival (OS) in men with high-volume, metastatic hormone-sensitive prostate cancer (mHSPC). Although the vast majority of men initially respond to D-ADT, most will progress and develop castration-resistant prostate cancer (CRPC). Little is known about the optimal treatment sequence for men with progressive disease on D-ADT.
PATIENT AND METHODS
Retrospective analysis of consecutive mHSPC patients treated with ≥3 cycles of D-ADT at Cleveland Clinic and University of Wisconsin-Madison was undertaken. The primary end-points included radiographic progression free survival (rPFS) and OS with first-line treatment for metastatic CRPC (mCRPC).
RESULTS
Final analysis included 136 patients, median age 65 (range 35-86), 77% GS ≥ 8, and 79% with high-volume disease who received ≥3 cycles of docetaxel. Undetectable PSA values at 12 and 24 months were observed in 32% and 25% of patients, respectively. Median time to CRPC (biochemical, clinical, or radiographic) was 19.6 months (16.6-22.6). Sixty patients (44%) received ≥1 treatment for CRPC: 48 patients (80%) received a second-generation hormonal therapy (sHT). Among these, 22 received abiraterone acetate, 20 enzalutamide, and six a novel CYP-17 inhibitor on trial (ASN-001). Five patients (8%) received sipuleucel-T; four (7%) radium-223, five (8%) chemotherapy (two carboplatin-based, two single agent cabazitaxel, one single agent docetaxel) and three other. Patients receiving sHT as the first treatment for mCRPC had a median rPFS of 9.0 months (95%CI, 6.9-11.2) compared with 3.0 months (95%CI, 1.5-4.5) for patients who received a non-sHT (P = 0.024). The choice of first therapy for mCRPC was independent of GS (P = 0.909), visceral disease (P = 0.690) and time to CRPC (P = 0.844). Longer OS correlated with time to CRPC (P = 0.010) and first treatment for CRPC with sHT (P = 0.005).
CONCLUSIONS
For patients with progressive disease on D-ADT, subsequent treatment with a sHT is associated with a longer rPFS and OS.
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2018
2018
2018
BACKGROUND
Tobacco companies are introducing new 'heat-not-burn' cigarettes in dozens of countries. Historically, these products failed commercially, and independent researchers contested their health claims. The most prominent early heat-not-burn cigarette was RJ Reynolds's (RJR's) Premier, introduced in the USA in 1988. Curiously, endorsed Premier as a 'near-perfect low tar cigarette' in a 1991 editorial, 2 years after Premier had been removed from the market. We examined the context of this endorsement.
METHODS
To ascertain what RJR knew about this endorsement, we systematically searched and analysed previously secret RJR documents in public archives and triangulated the industry document data with other published work.
RESULTS
RJR had a long-standing interest in collaborating with outside scientists to endorse potentially reduced harm cigarettes. The author of editorial had previously corresponded with RJR regarding Premier's health effects and market potential. Internally, RJR regarded 's editorial, its stance on novel tobacco products, and its endorsement of Premier as major successes. While the editorial came too late to save Premier, RJR saw future business opportunities for novel products if endorsed by health authorities.
CONCLUSIONS
Endorsement by high-impact medical journals and health authorities may be critical in helping heat-not-burn' products succeed where previous attempts have failed. Conflicts of interest influenced these endorsements in the past. Health leaders and academic journals should consider both conflicts of interest and the ethics of endorsing tobacco product substitution, as tobacco companies simultaneously work to promote cigarette smoking and undermine tobacco control globally.
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