Dataset Information

Temsirolimus Maintenance Therapy After Docetaxel Induction in Castration-Resistant Prostate Cancer.

ABSTRACT:

Lessons learned

Temsirolimus maintenance therapy after docetaxel induction chemotherapyis safe in patients with castration-resistant prostate cancer, although biochemical or tumor responses are rare;does not diminish quality of life; anddelays radiological and/or symptomatic progression by approximately 6 months.

Background

No standard therapy is available for men with castration-resistant prostate cancer (CRPC) who have responded to docetaxel and do not yet have disease progression. Hence, we designed a single-arm phase II trial to explore whether the mTOR inhibitor temsirolimus can maintain the response to docetaxel without compromising quality of life.

Methods

After successful docetaxel induction (75 mg/m(2) every 3 weeks; 6-10 cycles), 21 CRPC patients underwent temsirolimus maintenance treatment (25 mg weekly; 4 weeks per cycle). The primary endpoint was the time to treatment failure (TTTF) (i.e., radiological and/or symptomatic progression). The secondary endpoints included the tumor response rate (RECIST 1.0), safety (National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0), quality of life (Functional Assessment of Cancer Therapy-Prostate [FACT-P]), pain (Present Pain Intensity [PPI] scale), prostate-specific antigen (PSA) parameters, including time to PSA progression (TTPP) according to Prostate Cancer Clinical Trials Working Group criteria, and serial enumeration of circulating endothelial cells (CECs) and endothelial progenitor cells (CEPs).

Results

Patients received a median of 7 cycles of temsirolimus (range, 1-28), resulting in a median TTTF of 24.3 weeks (95% confidence interval [CI], 16.1-33.0), 1 partial tumor response (4.8%), 1 PSA response (4.8%), and a median TTPP of 12.2 weeks (95% CI, 7.8-23.9). Grade 3-4 adverse events were infrequent, and FACT-P and PPI scores remained stable during treatment. CECs did not predict clinical benefit, and CEPs were not consistently detectable.

Conclusion

Temsirolimus maintenance therapy after successful docetaxel induction is feasible, does not adversely affect quality of life, and, in this exploratory single-arm phase II study, resulted in a median TTTF of 24.3 weeks.

SUBMITTER: Emmenegger U

PROVIDER: S-EPMC4679087 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Publications

Temsirolimus Maintenance Therapy After Docetaxel Induction in Castration-Resistant Prostate Cancer.

Emmenegger Urban U Booth Christopher M CM Berry Scott S Sridhar Srikala S SS Winquist Eric E Bandali Nesan N Chow Annabelle A Lee Christina C Xu Ping P Man Shan S Kerbel Robert S RS Ko Yoo-Joung YJ

The oncologist 20151105 12

<h4>Lessons learned</h4>Temsirolimus maintenance therapy after docetaxel induction chemotherapyis safe in patients with castration-resistant prostate cancer, although biochemical or tumor responses are rare;does not diminish quality of life; anddelays radiological and/or symptomatic progression by approximately 6 months.<h4>Background</h4>No standard therapy is available for men with castration-resistant prostate cancer (CRPC) who have responded to docetaxel and do not yet have disease progressi ...[more]

PMID: 26542984

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Project description:BACKGROUND:Multiple androgens drive prostate cancer progression and higher pre-treatment levels of androgens, even within the castrate range, have been previously shown to be associated with an improved overall survival (OS) in mCRPC. Docetaxel impairs microtubules, has androgen receptor (AR) inhibitory effects and is used in both the castration resistant and sensitive settings, where androgen dynamics may impact outcome. The present analysis evaluates the association of decline in serum androgen levels (Testosterone (T), Androstenedione (A) and DHEA in docetaxel-treated mCRPC patients with OS. METHODS:Data from 1050 men treated on CALGB 90401 with docetaxel, prednisone and either bevacizumab or placebo were evaluated. Eligibility required progressive mCRPC and no prior chemotherapy. Pre-treatment, 6 week and progression serum assays for T, A and DHEA were performed via tandem Liquid Chromatography-Mass Spectrometry (LC-MS/MS). Changes in T, A and DHEA levels from baseline to 6 weeks were calculated as the ratio of 6-week over baseline. The proportional hazards model was used to assess the prognostic significance of changes in T, A, and DHEA from baseline to 6 weeks in predicting OS adjusting for known prognostic factors. RESULTS:Median baseline values for T, A, and, DHEA were 1.0, 13.5, and 8.1?ng/dL respectively while 6 week levels were 0.64, 7.0, and 6.8?ng/dL respectively. Median OS for low testosterone decline is 20.9 months vs 26.3 months for high testosterone decline. In multivariable analysis including known prognostic variables, change in testosterone levels was independently associated with greater OS; the hazard ratio for death with each unit increase in the 6-week/baseline ratio is 1.02 (95% CI?=?1.01-1.03, p?=?0.001). Decline in A and DHEA were not significant predictors of OS. In multivariable analysis change in the serum changes did not predict PFS however the ratio of T at 6-weeks over baseline was prognostic of ?50% decline in PSA with an odds ratio of 0.93 (95% CI?=?0.85-0.98, p-value?=?0.039). CONCLUSIONS:Declines in testosterone during docetaxel treatment is associated with a longer survival, consistent with a favorable prognostic significance of higher serum androgens in the CRPC.

Project description:Background:Sarcopenia is a geriatric syndrome that is characterized by the gradual muscle loss and frailty in the elderly. Meanwhile, the prevalence of prostate cancer is on the rise worldwide. Mainstay treatments for metastatic prostate cancer are androgen-deprivation therapy and taxane-based chemotherapy. Owing to the indolent nature of prostate cancer, these treatments tend to be long-lasting, giving rise to the problem of tolerance to the treatments. Especially given the fact that long-term chemotherapy is closely associated with muscle loss, we aimed to elucidate the correlation between chemotherapy and sarcopenia in the clinical setting. Materials and methods:This study was a retrospective study. Participants with castration-resistant prostate cancer were recruited from November 2009 to September 2015.Participants were recruited at two hospitals, Juntendo and Teikyo University Hospital, Tokyo, Japan.Participants were 77 Japanese males with castration-resistant prostate cancer who underwent docetaxel chemotherapy.Sarcopenia was defined as L3-psoas muscle index < 5.7 cm2/m2. We statistically investigated whether the existence of sarcopenia has an impact on the survival time, and identified potential covariates that affect it. Results:Out of 77 patients, 26 patients (34%) were diagnosed as sarcopenia. Analysis showed that sarcopenia is independently associated with mortality risk (hazards ratio = 2.74, P = 0.0055). Sarcopenic patients showed significant decrease in body mass index, pretreatment hemoglobin, C-related protein, and L3-psoas muscle index as compared with nonsarcopenic patients. The median observation period was 499 days (330-790). Thirty-five patients (45%) died of prostate cancer during that period. Sarcopenic patients showed significantly shorter survival time after the initiation of docetaxel treatments (P = 0.0055). Conclusion:Sarcopenia is an independent predictive factor for a poor tolerance to docetaxel treatment. Given that cessation of the treatment leads to death from the disease, our study identified sarcopenia as an independent factor that raises mortality risk.

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Dataset Information

Temsirolimus Maintenance Therapy After Docetaxel Induction in Castration-Resistant Prostate Cancer.

Lessons learned

Background

Methods

Results

Conclusion

Publications

Temsirolimus Maintenance Therapy After Docetaxel Induction in Castration-Resistant Prostate Cancer.

Similar Datasets

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