Richard Y. Lam

Intermittent Use of Testosterone Inactivating Pharmaceuticals Using Finasteride Prolongs the Time Off Period

PURPOSE Men with prostate cancer treated intermittently with TIP benefit from improved quality of life when TOP with recovered testosterone is prolonged. We examined factors influencing the duration of TOP. MATERIALS AND METHODS We retrospectively reviewed the charts of 101 men treated with intermittent TIP in a 9-year period. Men with positive bone scan, men in whom a PSA nadir of less than 0.1 ng/ml on TIP failed to be achieved and maintained and men in whom testosterone failed to recover to greater than 150 ng/dl during the first 12 months of TOP were excluded. Potential factors predicting prolonged TOP or accelerated time to AIPC were studied with Cox regression analysis. RESULTS Patient characteristics were clinical stage T1c-T2a in 51 and T2b-T3b in 11, PSA relapse in 29, and T3c, D0 or D1 in 10. Median PSA was 7.6 ng/ml, Gleason score was 3 + 4 = 7 and TIP duration was 15.8 months. The 60 group 1 patients received finasteride and the 41 in group 2 received no finasteride. Median TOP in groups 1 and 2 was 31 and 15 months, respectively, using Kaplan-Meier analysis. Cox regression analysis indicated that longer TIP, finasteride and increased age predicted longer TOP. A slow PSA decrease while on TIP, higher baseline PSA and increased Gleason score predicted shorter TOP. Cox regression analysis indicated that only higher clinical stage but not finasteride predicted the earlier onset of AIPC. CONCLUSIONS Finasteride doubles the duration of TOP. AIPC was not increased by finasteride after almost 9 years of observation.

Primary Intermittent Androgen Deprivation As Initial Therapy for Men with Newly Diagnosed Prostate Cancer

BACKGROUND The purpose of this study was to describe the long-term incidence of cancer progression and mortality in men with localized prostate cancer treated with primary androgen deprivation (AD). METHODS A retrospective chart review, from a medical oncology practice specializing in prostate cancer, was conducted of 73 men eligible for surgery or radiation treated with induction AD. Entry criteria consisted of a minimum of 9 months of induction AD, treatment initiation before 1999, clinical stage < T3, and outcome defined as the incidence of delayed local therapy, cancer progression, cancer mortality, and mortality from other causes. RESULTS Median follow-up was 12 years. Fifteen men were at low risk, 38 were at intermediate risk, and 20 were at high risk. Three men (4%) experienced metastatic disease and died of prostate cancer after 3.5, 7.7, and 11 years, respectively. Two men were in the intermediate-risk category and 1 was high risk. Nineteen men (26%) died of non-prostate cancer causes. None had metastatic disease at the time of death. Of the remaining 51 survivors, none has experienced bone metastasis. Twenty-one men (29%) required no further therapy after the first induction course of AD. Twenty-four men (33%) maintained a prostate-specific antigen (PSA) level < 5.0 ng/mL with 2 to 5 cycles of intermittent AD. Twenty-eight men (38%) underwent delayed local therapy after a median of 5.5 years. Median follow-up after local therapy was 6.2 years. Three of these men experienced subsequent rising PSA levels but none has progressed to bone metastasis. Sixteen of 20 men (80%) in the high-risk category but only 12 of 53 men (23%) in the low- and intermediate-risk categories had delayed local therapy. CONCLUSIONS Primary intermittent AD is feasible for men with localized prostate cancer. Men who are younger and men with high-risk disease undergo delayed local therapy more frequently.

Phase I clinical trial of sipuleucel-T combined with escalating doses of ipilimumab in progressive metastatic castrate-resistant prostate cancer

Background Sipuleucel-T (SIP-T), which functions by stimulating cancer-specific dendritic cells, prolongs survival in men with prostate cancer. Ipilimumab (IPI) achieved a borderline survival advantage in a large randomized trial. SIP-T and IPI are potentially synergistic. Patients and Methods Nine men with progressive metastatic castrate-resistant prostate cancer (mCRPC) were treated prospectively with SIP-T followed immediately by IPI with one of the following doses of IPI: 1 mg/kg at 1 week after SIP-T; 1 mg/kg at 1 and 4 weeks after SIP-T; or 1 mg/kg at 1, 4, and 7 weeks after SIP-T. Three patients were evaluated at each level. Cancer-specific immunoglobulins directed at granulocyte-macrophage-colony-stimulating factor/prostatic acid phosphatase (PAP) fusion protein (PA2024) and PAP were measured prior to SIP-T, after SIP-T, 1 week after IPI, every other month for 5 months, then every 3 months for an additional 12 months. Results Adverse events of SIP-T were consistent with previous reports. IPI only caused a transient grade 1 rash in one patient. Median age, Gleason score, and number of previous hormonal interventions were 77 years, 8, and 3, respectively. Eight men had bone metastases and one had lymph node metastasis. Statistically significant increases in serum immunoglobulin G (IgG) and IgG-IgM specific for PA2024 and PAP occurred after SIP-T. An additional statistically significant increase in the aforementioned immunoglobulins – above the levels achieved by SIP-T – occurred after IPI. Median clinical follow-up was 36 months (range: 26–40). Three patients died from progressive disease after 9, 18, and 20 months. Out of the remaining six patients, five of them needed further treatment that included abiraterone acetate, enzalutamide, radium-223 dichloride, and spot radiation. One patient had an undetectable PSA, who did not receive any other treatment except spot radiation. Median PSA at last follow-up for the surviving patients was 3.8 (range: 0.6–7.47). Conclusion In this small trial, the addition of IPI to SIP-T was well tolerated. IPI increased immunoglobulins specific for the PA2024 protein and PAP above the level achieved with SIP-T alone.

Primary androgen deprivation (AD) followed by active surveillance (AS) for newly diagnosed prostate cancer (PC): A retrospective study.

Active surveillance (AS) is only recommended for Low‐Risk prostate cancer (PC) with <34% biopsies positive. Studies describing the long‐term outcome of men treated with androgen deprivation (AD) followed by AS are sparse.