The Impact of Doxycycline as an Adjunctive Therapy on Prostate-Specific Antigen, Quality of Life, and Cognitive Function in Metastatic Prostate Cancer Patients: A Phase II Randomized Controlled Trial
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Study Subjects
2.3. Outcome Measures and Follow-Up
2.4. Blinding
2.5. Sample Size
2.6. Structure–Activity Relationship Analysis
2.7. Statistical Analysis
3. Results
3.1. Participants
3.2. Treatment Effects on Prostate-Specific Antigen (PSA) Levels
3.3. Change in PSA Levels
3.4. Therapeutic Response (≥50% Reduction in PSA Levels)
3.5. Multivariate Logistic Regression Analysis
3.6. Quality of Life and Cognitive Decline
3.7. In Silico Analysis
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | All (n = 45) | Placebo (n = 24) | Doxycycline (n = 21) | p-Value |
Age (years) | 73.0 (70.0–78.5) | 73.0 (70.0–78.0) | 73.0 (69.5–80.0) | 0.909 * |
BMI | 28.3 (26.5–30.7) | 28.0 (26.7–30.0) | 28.8 (26.7–31.2) | 0.542 * |
Gleason score | 8.1 (7.2–8.5) | 8.2 (7.5–8.5) | 8.0 (7.0–8.2) | 0.852 * |
Glucose (mg/dL) | 106.0 (91.0–122.0) | 100.5 (89.5–120.7) | 110.0 (91.7–124.2) | 0.391 * |
Docetaxel | 75.6% | 83.3% | 66.7% | 0.299 ** |
Poor Quality of Life | 46.2% | 47.6% | 44.4% | 0.999 ** |
MMSE score | 22.0 (21.0–25.0) | 23.0 (20.2–25.7) | 22.0 (21.0–23.5) | 0.549 * |
Control | Doxycycline | ||||||
---|---|---|---|---|---|---|---|
PSA | Median | Q1 | Q3 | Median | Q1 | Q3 | p-Value * |
Baseline | 18.50 | 11.7500 | 32.00 | 17.00 | 7.50 | 30.00 | 0.473 |
3 months | 17.00 | 9.2250 | 28.00 | 9.00 | 3.50 | 18.00 | 0.059 |
6 months | 16.0 | 7.2500 | 22.00 | 7.00 | 1.35 | 14.20 | 0.043 |
P Baseline vs. 3 months ** | <0.001 | <0.001 | |||||
P Baseline vs. 6 months ** | <0.001 | <0.001 |
PSA Change | Placebo | Doxycycline | p-Value * | ||||
---|---|---|---|---|---|---|---|
Median | Q1 | Q3 | Median | Q1 | Q3 | Control vs. Experimental | |
3 months | −2.80 | −7.25 | −1.00 | −8.10 | −10.00 | −2.75 | <0.001 |
6 months | −5.65 | −11.75 | −1.34 | −12.00 | −14.00 | −4.85 | <0.001 |
Therapeutic Response | 95% CI | |||||||
---|---|---|---|---|---|---|---|---|
n | No | Yes | RR | Lower | Upper | p-Value | ||
3 months | Placebo | 24 | 87.5% | 12.5% | Reference | |||
Doxycycline | 21 | 66.7% | 33.3% | 3.50 | 0.77 | 15.87 | 0.151 | |
6 months | Placebo | 24 | 79.2% | 20.8% | Reference | |||
Doxycycline | 21 | 28.6% | 71.4% | 9.50 | 2.42 | 37.24 | 0.001 |
CI95% | ||||
---|---|---|---|---|
AdRR | Lower | Upper | p-Value | |
Basal PSA | 0.977 | 0.940 | 1.014 | 0.221 |
Age | 0.976 | 0.870 | 1.096 | 0.686 |
Docetaxel | 0.797 | 0.127 | 5.002 | 0.808 |
Doxycycline | 10.309 | 2.359 | 45.055 | 0.002 |
Poor Quality of Life | All | Placebo | Doxycycline | p-Value * |
---|---|---|---|---|
Baseline | 46.20% | 47.6% | 44.4% | 0.999 |
3 months | 30.8% | 47.6% | 11.1% | 0.018 |
6 months | 28.6% | 42.9% | 7.1% | 0.028 |
P Baseline vs. 3 m ** | 0.109 | 0.999 | 0.014 | |
P Baseline vs. 6 m ** | 0.090 | 0.763 | 0.014 |
Molecule | MW | Fraction Csp3 | # of Rotatable Bonds | # of H-Bond Acceptors | # of H-Bond Donors | MR | TPSA | iLOGP | XLOGP3 | WLOGP | MLOGP |
---|---|---|---|---|---|---|---|---|---|---|---|
Doxycycline | 444.43 | 0.41 | 1 | 9 | 6 | 110.91 | 181.62 | 1.43 | 1.19 | −0.5 | −2.08 |
Chlortetracycline | 478.88 | 0.41 | 2 | 9 | 6 | 115.23 | 181.62 | 1.92 | −0.62 | 0.33 | −1.6 |
Demeclocycline | 464.85 | 0.38 | 2 | 9 | 6 | 110.54 | 181.62 | 1.55 | −0.56 | −0.06 | −1.82 |
Minocycline | 457.48 | 0.43 | 3 | 8 | 5 | 118.57 | 164.63 | 1.66 | 0.05 | 0.19 | −1.6 |
Oxytetracycline | 460.43 | 0.41 | 2 | 10 | 7 | 111.95 | 201.85 | 0.55 | −0.7 | −1.51 | −2.85 |
Tigecycline | 585.65 | 0.52 | 8 | 10 | 7 | 154.95 | 205.76 | 2.23 | −0.19 | 0.32 | −2.05 |
Lymecycline | 602.63 | 0.52 | 11 | 13 | 9 | 151.24 | 242.98 | 0 | −4.3 | −0.56 | −4.73 |
Metacycline | 442.42 | 0.32 | 2 | 9 | 6 | 110.65 | 181.62 | 1.55 | −0.24 | −0.44 | −2.16 |
Rolitetracycline | 527.57 | 0.52 | 5 | 10 | 6 | 139.04 | 170.87 | 2.69 | −0.28 | −0.02 | −1.4 |
Bicalutamide | 430.37 | 0.22 | 7 | 9 | 2 | 93.86 | 115.64 | 1.95 | 2.31 | 5.34 | 2.47 |
Flutamide | 276.21 | 0.36 | 5 | 6 | 1 | 64.19 | 74.92 | 1.85 | 3.35 | 4.17 | 2.03 |
Finasteride | 372.54 | 0.83 | 3 | 2 | 2 | 113.18 | 58.2 | 3.42 | 3.03 | 3.43 | 3.46 |
Dutasteride | 528.53 | 0.63 | 5 | 8 | 2 | 129.94 | 58.2 | 3.85 | 5.37 | 8.31 | 5.42 |
Cyproterone acetate | 416.94 | 0.71 | 3 | 4 | 0 | 111.96 | 60.44 | 3.41 | 3.64 | 4.61 | 3.71 |
Docetaxel | 807.88 | 0.56 | 14 | 14 | 5 | 205.25 | 224.45 | 3.33 | 2.81 | 2.94 | 1.06 |
Leuprolide | 1237.47 | 0.24 | 20 | 16 | 1 | 1590.8 | 397.28 | −3.92 | −3.92 | −3.83 | −3.89 |
Goserelin | 1249.47 | 0.25 | 20 | 16 | 1 | 1603.7 | 397.47 | −3.91 | −3.91 | −3.84 | −3.9 |
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Guzmán-Esquivel, J.; Garcia-Garcia, H.S.; Hernández-Fuentes, G.A.; Venegas-Ramírez, J.; Barajas-Mejía, C.D.; Garza-Veloz, I.; Martinez-Fierro, M.L.; Magaña-Vergara, N.E.; Guzmán-Solórzano, J.A.; Calvo-Soto, P.; et al. The Impact of Doxycycline as an Adjunctive Therapy on Prostate-Specific Antigen, Quality of Life, and Cognitive Function in Metastatic Prostate Cancer Patients: A Phase II Randomized Controlled Trial. Pharmaceutics 2025, 17, 404. https://doi.org/10.3390/pharmaceutics17040404
Guzmán-Esquivel J, Garcia-Garcia HS, Hernández-Fuentes GA, Venegas-Ramírez J, Barajas-Mejía CD, Garza-Veloz I, Martinez-Fierro ML, Magaña-Vergara NE, Guzmán-Solórzano JA, Calvo-Soto P, et al. The Impact of Doxycycline as an Adjunctive Therapy on Prostate-Specific Antigen, Quality of Life, and Cognitive Function in Metastatic Prostate Cancer Patients: A Phase II Randomized Controlled Trial. Pharmaceutics. 2025; 17(4):404. https://doi.org/10.3390/pharmaceutics17040404
Chicago/Turabian StyleGuzmán-Esquivel, José, Hossana S. Garcia-Garcia, Gustavo A. Hernández-Fuentes, Jesús Venegas-Ramírez, Carlos D. Barajas-Mejía, Idalia Garza-Veloz, Margarita L. Martinez-Fierro, Nancy E. Magaña-Vergara, José A. Guzmán-Solórzano, Patricia Calvo-Soto, and et al. 2025. "The Impact of Doxycycline as an Adjunctive Therapy on Prostate-Specific Antigen, Quality of Life, and Cognitive Function in Metastatic Prostate Cancer Patients: A Phase II Randomized Controlled Trial" Pharmaceutics 17, no. 4: 404. https://doi.org/10.3390/pharmaceutics17040404
APA StyleGuzmán-Esquivel, J., Garcia-Garcia, H. S., Hernández-Fuentes, G. A., Venegas-Ramírez, J., Barajas-Mejía, C. D., Garza-Veloz, I., Martinez-Fierro, M. L., Magaña-Vergara, N. E., Guzmán-Solórzano, J. A., Calvo-Soto, P., Avila-Zamora, O. N., Fuentes-Murguia, M., Ceja-Espíritu, G., & Delgado-Enciso, I. (2025). The Impact of Doxycycline as an Adjunctive Therapy on Prostate-Specific Antigen, Quality of Life, and Cognitive Function in Metastatic Prostate Cancer Patients: A Phase II Randomized Controlled Trial. Pharmaceutics, 17(4), 404. https://doi.org/10.3390/pharmaceutics17040404