Effect of Docetaxel in Patients With Hormone-Dependent Prostate-Specific Antigen Progression After Local Therapy for Prostate Cancer

Goodin, Susan; Medina, Patrick J.; Capanna, Terry; Shih, Weichung Joe; Abraham, Sybil; Winnie, Jessica; Doyle-Lindrud, Susan; Todd, Mary B.; DiPaola, Robert S.

doi:10.1200/jco.2005.11.111

Cited by 26 publications

(13 citation statements)

References 16 publications

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“…The differences shown in TTP and OS might be due to the fact that, patients in our study had more advanced disease when entering study. We found a mean PSA of 448 microgram/L at baseline, compared to mean PSA of 114 microgram/L in the B-arm of TAX 327, suggesting that patients receiving DGP had poorer prognosis [6,8,17]. In our study 98% had bone metastasis and 56% had visceral metastasis, whereas patients in the B-arm of Tax 327 patients had bone involvement in 90% of cases and visceral metastasis in 22% of cases [6].…”

Section: Discussioncontrasting

confidence: 44%

Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

Buch-Hansen

Bentzen

Hansen

et al. 2009

Cancer Chemother Pharmacol

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Purpose:We assessed the efficacy and toxicity of a fixed dose of docetaxel and prednisone, combined with escalating doses of gemcitabine (DGP). The primary endpoint was PSA response. Methods:Fifteen patients (pts) were enrolled in the phase I and 50 pts entered the phase II. Pts were given DGP, maximum of 8 courses, until progression or unacceptable toxicity. Docetaxel 75 mg/m 2 was administered intravenously day 1, gemcitabine was given day 1 and 8 in doses increasing from 600 to 1,000 mg/m 2 every third week. Pts had castrate refractory metastatic prostate cancer (CRMPC), adequate function of liver, kidney and bone marrow; ECOG performance status ≤2 and were chemotherapy-naïve. Results:Median age was 64 range (49-77). Twenty-one (42%) were PS 0, 26 (52%) were PS 1 and 3 (6%) were PS 2. The median pre-treatment PSA was 448 (12-4.580). No dose limiting toxicity was observed even with the highest dose level in the phase I part of the study. In the phase II part, PSA response was observed in 37(74%) pts. Twenty-four (48%) pts had measurable disease; 12 (50%) had partial remission, 5 (21%) had stable disease, 7 (29%) were not evaluable. Time to progression (TTP) was 7.9 months and overall survival (OS) was 13.9 months. Thirty-seven pts (74%) developed neutropenia, non-haematological toxicity was modest. Conclusions:The PSA response rate was promising and the toxicity of DGP was manageable; however OS was comparable to results of treatment with single agent docetaxel.

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Section: Discussioncontrasting

confidence: 44%

Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

Buch-Hansen

Bentzen

Hansen

et al. 2009

Cancer Chemother Pharmacol

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“…Thus, PSA induction due to calcitriol therapy may be a marker of cellular transformation to a more indolent phenotype. Further, the observed PSA increases may be due to a transient stress response seen in this and other therapies such as docetaxel (26). Last, more recent data have shown that the PSA protein has significant biological properties that may reduce tumor invasiveness.…”

Section: Discussionmentioning

confidence: 84%

Effect of Calcitriol on Prostate-Specific Antigen In vitro and in Humans

Beer

Garzotto

Park

et al. 2006

Clinical Cancer Research

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Background: Calcitriol, the natural ligand for the vitamin D receptor, has significant potential in prostate cancer treatment. Measurementofits antineoplastic activityinprostate cancerclinicaltrials may be complicated by effects of calcitriol on prostate-specific antigen (PSA) production.We examined the effects of calcitriol at similar concentration on cell proliferation, androgen receptor (AR) expression, and PSA production in vitro and on PSA concentrations in prostate cancer patients. Experimental Design: LNCaP prostate cancer cell proliferation was examined by cell counts 6 days after exposure to a range of concentrations of calcitriol. AR and PSA protein was quantified in LNCaP cells over 96 hours after exposure to 1 nmol/L calcitriol. Serum PSA and free PSA was serially measured by immunoassay over a period of 8 days in patients with hormone-nai « ve prostate cancer after a single dose of 0.5 Ag/kg calcitriol. Results: Calcitriol treatment resulted in dose-dependent growth inhibition of LNCaP with f50% growth inhibition at the clinically achievable concentration of 1nmol/L. Time-dependent up-regulation of AR expression and of PSA production in LNCaP cells was shown at the same concentration. No significant change in serum PSA or free PSA over 8 days was seen in eight subjects treated with a single dose of 0.5 Ag/kg calcitriol. The analysis was powered to detect a 1.23-fold change between the baseline and day 8 serum PSA. Conclusions: At clinically achievable concentrations, calcitriol inhibits growth and induces AR and PSA expression in LNCaP cells.We did not detect similar changes in serum PSA or free PSA in patients exposed to similar concentrations of calcitriol.Thus, a PSA flare, predicted by preclinical systems, is unlikely to occur in patients and therefore unlikely to complicate interpretation of clinical trial outcomes.There is ample preclinical evidence supporting the investigation of vitamin D receptor ligands in prostate cancer therapy. Both tissue culture systems (1 -6) and mouse models (6 -8) show the inhibitory activity of vitamin D receptor ligands in prostate cancer. Physiologic levels of calcitriol range between 0.05 and 0.16 nmol/L; however, significant growth inhibition requires calcitriol concentrations of z1 nmol/L (416.7 pg/mL) in most studies (4, 5).Encouraging preclinical data have led to the development of several clinical trials of calcitriol in prostate cancer, all of which sought to escalate the doses of calcitriol in the hope of achieving therapeutic concentrations. A modest degree of dose escalation was possible with daily dosing before hypercalcemia and/or hypercalcuria was encountered (9, 10). Weekly dosing of calcitriol allowed significant dose escalation and peak serum concentrations of calcitriol above 1 nmol/L were achievable with this approach (11,12).Activity of new agents in prostate cancer is routinely assessed by measuring changes in serum prostate-specific antigen (PSA) levels (13). Indeed, recent data suggest that in androgenindependent prostate cancer, p...

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“…Goodin et al [44] treated 25 men with 70 mg/M 2 every 3 weeks for eight planned cycles. PSA declined in 18 men without any signifi cant decline in serum testosterone levels.…”

Section: Chemotherapy For Biochemical Relapse After Defi Nitive Localmentioning

confidence: 99%

Does chemotherapy have a role before hormone-resistant disease develops?

Dean¹,

Higano

2009

Curr Urol Rep

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Recent studies have demonstrated a survival benefit for chemotherapy in metastatic hormone-resistant prostate cancer. In other malignancies such as breast or colorectal cancer, use of active chemotherapy regimens earlier in the course of the disease has resulted in improvements in disease-free and overall survival. This review discusses the status of chemotherapy in prostate cancer and addresses evidence regarding the use of chemotherapy in hormone-sensitive disease, alone and in combination with androgen deprivation therapy.

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Effect of Docetaxel in Patients With Hormone-Dependent Prostate-Specific Antigen Progression After Local Therapy for Prostate Cancer

Cited by 26 publications

References 16 publications

Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

Effect of Calcitriol on Prostate-Specific Antigen In vitro and in Humans

Does chemotherapy have a role before hormone-resistant disease develops?

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