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ABSTRACT: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Previous studies have reported better outcomes in cancer patients that enrolled in clinical trials, suggesting that trial participation in itself might be beneficial. We investigated the potential positive effect of clinical trial participation on survival outcomes of patients with metastatic castration-resistant prostate cancer who were treated with first-line docetaxel-containing chemotherapy. After accounting for potential baseline inequalities, participation in a clinical trial itself was associated with significantly longer overall survival in these patients. OBJECTIVE: • To study differences in baseline characteristics and outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line docetaxel-containing chemotherapy on prospective clinical studies (trial participants) versus those receiving this therapy outside of a clinical study (non-participants). PATIENTS AND METHODS: • Records from 247 consecutive chemotherapy-naive patients who were treated with docetaxel-containing chemotherapy for mCRPC at a single high-volume centre from 1998 to 2010 were reviewed. • All patients received docetaxel either as clinical trial participants (n= 142; 11 separate studies) or as non-participants (n= 105). • Univariable and multivariable Cox regression models predicted overall survival after chemotherapy initiation. RESULTS: • There was no significant difference between trial participation and non-participation with respect to patient age, type of primary treatment, tumour grade or clinical stage. • Multivariable analyses showed a significantly lower risk of all-cause mortality (hazard ratio 0.567; P= 0.027) among trial participants vs non-participants. CONCLUSIONS: • Patients that were treated with docetaxel for mCRPC showed a significantly longer overall survival when enrolled in a clinical trial. • Improved survival in trial participants may reflect the better medical oversight typically seen in patients enrolled in trials, more regimented follow-up schedules, or a positive effect on caregivers' attitudes because of greater contact with medical services. • With the retrospective nature of this analysis and the small study population, prospective studies are needed to validate the present findings and to further investigate the relationship between clinical trial participation and outcomes.
BJU International 06/2012; · 2.84 Impact Factor
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ABSTRACT: Sunitinib is a standard treatment for metastatic renal cell carcinoma (mRCC). The neutrophil to lymphocyte ratio (NLR), an index of systemic inflammation, is associated with outcome in several cancer types.
To study the association of pre-treatment neutrophil to lymphocyte ratio with response rate, progression free survival (PFS) and overall survival (OS) of patients treated with sunitinib for mRCC.
We retrospectively studied an unselected cohort of patients with mRCC, who were treated with sunitinib. Logistic regression model was used to analyse response rate. Cox regression models were fitted to identify risk factors associated with PFS and OS. We investigated how pre-treatment NLR is associated with these clinical outcomes after adjusting for confounding covariates. Regression tree for censored data method was used to find the best NLR cut-off value.
Between 2004 and 2011, 133 patients with mRCC were treated with sunitinib. One hundred and nine were included in the NLR analysis, from which were excluded patients without available data on pre-treatment NLR or with comorbidities/recent treatments known to be associated with a change of blood counts. Factors associated with PFS were low NLR ≤ 3 (HR = 0.285, p < 0.001), past nephrectomy (HR = 0.38, p = 0.035), sunitinib dose reduction/treatment interruption (HR = 0.6, p = 0.014) and the use of antiotensin system inhibitors (HR = 0.537, p = 0.008). Low NLR ≤ 3 was associated with OS (HR = 0.3, p = 0.043).
In patients with mRCC treated with sunitinib, pre-treatment NLR may be associated with PFS and OS. This should be investigated prospectively, and if validated applied in clinical practice and clinical trials.
European journal of cancer (Oxford, England: 1990) 01/2012; 48(2):202-8. · 4.12 Impact Factor
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ABSTRACT: Adrenal/intratumoral androgen biosynthesis contributes to ligand-dependent androgen receptor activation in metastatic castration-resistant prostate cancer (mCRCP). Compounds targeting CYP-17 hydroxylase and lyase, as ketoconazole and abiraterone, block adrenal/intratumoral androgen biosynthesis, and are used as sequential endocrine approaches in mCRCP. We aimed to describe contemporary experience and association of clinical factors with Prostate specific antigen (PSA) response and disease progression, in mCRPC progressing on GnRH-agonist, antiandrogen, antiandrogen withdrawal, and treated with ketoconazole.
Data were retrospectively analyzed in all mCRPC patients treated with ketoconazole. Patients continued GnRH-agonist, and treated with ketoconazole 200-400 mg 3× a day until dose-limiting toxicity or disease progression. A multivariate cox regression model was used to identify clinical factors associated with PSA response and disease progression.
From 1999 to 2010, 114 mCRPC patients were treated with ketoconazole. With a median follow-up time of 31 months (range 5-129), 25 patients (22%) had grade 3/4 toxicity, most commonly fatigue, abdominal discomfort, nausea, and dizziness. Sixty-one patients (54%) had ≥50% PSA decline. Median time to progression was 8 months (range 1-129). Factors associated with PSA response and disease progression were response to prior antiandrogen (≥6 vs. <6 months), pre-treatment PSADT (≥3 vs. <3 months) and extent of disease (limited-axial skeleton and/or nodal vs. extensive-appendicular skeleton and/or visceral).
Ketoconazole is effective and safe in mCRPC. Prior response to antiandrogen, pre-treatment PSADT, and disease extent are associated with PSA response and disease progression, and further supports a therapeutic role in suppressing adrenal androgens in mCRPC.
The Prostate 06/2011; 72(4):461-7. · 3.48 Impact Factor
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ABSTRACT: Sunitinib is a standard treatment for metastatic renal cell carcinoma. Angiotensin system inhibitors, including angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, are widely used in hypertension, kidney disease and heart failure. Data suggests that they may inhibit tumourigenesis.
To study the effect of angiotensin system inhibitors on sunitinib treatment outcome in metastatic renal cell carcinoma.
We performed a retrospective study of an unselected cohort of patients with metastatic renal cell carcinoma who were treated with sunitinib. Patients were divided into angiotensin system inhibitors users (group 1) and non-users (group 2). The effect of angiotensin system inhibitors on objective response, time to disease progression and overall survival, was tested with adjustment for known confounding risk factors through logistic regression model and Cox regression model.
Between 2004 and 2010, 127 patients with metastatic renal cell carcinoma were treated with sunitinib, 44 group 1 and 83 group 2. The groups were balanced regarding known clinicopathologic prognostic factors. Objective response was partial response/stable disease 86% versus 72% and progressive disease 14% versus 28% (p=0.07) in group 1 versus 2, respectively. Median progression free survival was 13 versus 6 months (HR 0.537, p=0.0055), and median overall survival 30 versus 23 months (HR 0.688, p=0.21), in favour of group 1.
Angiotensin system inhibitors may improve the outcome of sunitinib treatment in metastatic renal cell carcinoma. This should be investigated prospectively, and if validated applied in clinical practise and clinical trials.
European journal of cancer (Oxford, England: 1990) 05/2011; 47(13):1955-61. · 4.12 Impact Factor
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ABSTRACT: We sought to determine the change of PSA doubling time (PSADT) and its association with disease progression during intermittent androgen deprivation (IAD) therapy for prostate cancer.
Data were retrospectively analyzed in 96 patients with biochemically relapsed prostate cancer (BRPC) treated with IAD since 1995. IAD consisted of LHRH-agonists ± antiandrogen given usually at PSA threshold (ng/ml) of 10-20, for 6-9 months. Cycles were repeated until the development of castration resistance. Mixed effects model was used to study PSADT change over cycles. Multivariate cox regression model was used to identify outcome-associated variables.
Patients received a mean of 2.8 treatment cycles over a mean follow-up time of 71 months. Fifty-seven (59%) remain on treatment and 39 (41%) developed PSA refractoriness (n = 8) or positive scans (n = 31). First off treatment interval PSADT (median 2.3 months) was significantly shorter than the baseline (median 7.34) but remained stable in subsequent cycles. Off treatment interval PSADT adjusted for testosterone recovery (median 3.7) was significantly longer than that based on all PSA determinations (median 2). Factors associated with disease progression were pre-treatment PSADT (≥6 vs. <6), first off treatment interval PSADT (≥3 vs. <3), and PSA nadir during the first treatment interval (<0.1 vs. ≥0.1).
During IAD for BRPC, PSADT becomes shorter, and is associated with testosterone recovery. PSADT before treatment and during the first off treatment interval is associated with disease progression. If prospectively validated these data may guide treatment with IAD and clinical trial design.
The Prostate 03/2011; 71(15):1608-15. · 3.48 Impact Factor
