Long-term clinical impact of PSA surge in castration-resistant prostate cancer patients treated with abiraterone.

BACKGROUND: Early changes in PSA have been evaluated in association to treatment outcome. The aim of this study was to assess PSA surge phenomenon in castration-resistant prostate cancer (CRPC) patients treated with abiraterone and to correlate those variations with long-term treatment outcome. PATIENTS AND METHODS: We retrospectively evaluated 330 CRPC patients in 11 Italian hospitals, monitoring PSA levels at baseline and every 4 weeks. Other clinical, biochemical and molecular parameters were determined at baseline. We considered PSA surge as PSA increase within the first 8 weeks from starting abiraterone more than 1% from baseline followed by a PSA decline. The log-rank test was applied to compare survival between groups of patients according to PSA surge. The impact of PSA surge on survival was evaluated by Cox regression analyses. RESULTS: A total of 330 patients with CRPC, median age 74 years (range, 45-90), received abiraterone (281 chemotherapy-treated and 49 chemotherapy-naïve). PSA surge was observed in 20 (7%) post-chemotherapy and 2 (4%) chemotherapy-naïve patients. For overall patients presenting PSA surge, timing of PSA peak from baseline was 5 ± 1.8 weeks and PSA rise from baseline was 21 ± 18.4%. The overall median follow-up was 23 months (range 1-62). No significant differences in progression-free survival and overall survival were observed between patients with and without PSA surge (P = 0.16 and =0.86, respectively). In addition, uni- and multivariate analyses showed no baseline factors related to PSA surge. CONCLUSION: PSA surge occurs in both chemotherapy-treated and chemotherapy-naïve patients treated with abiraterone resulting, however, in no long-term impact on outcome. Physicians and patients should be aware of PSA surge challenge to prevent a premature discontinuation of potentially effective therapy with abiraterone. Further larger and prospective studies are warranted to investigate this not infrequent phenomenon.

Systemic Immune-Inflammation Index Predicts the Clinical Outcome in Patients with mCRPC Treated with Abiraterone.

Background: A systemic immune-inflammation index (SII) based on neutrophil (N), lymphocyte (L), and platelet (P) counts has shown a prognostic impact in several solid tumors. The aim of this study is to evaluate the prognostic role of SII in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone post docetaxel. Patients and Methods: We retrospectively reviewed consecutive mCRPC patients treated with abiraterone after docetaxel in our Institutions. X-tile 3.6.1 software, cut-off values of SII, neutrophil-to-lymphocyte ratio (NLR) defined as N/L and platelets-to-lymphocyte ratio (PLR) as P/L. Overall survival (OS) and their 95% Confidence Intervals (95% CI) was estimated by the Kaplan-Meier method and compared with the log-rank test. The impact of SII, PLR, and NLR on overall survival (OS) was evaluated by Cox regression analyses and on prostate-specific antigen (PSA) response rates were evaluated by binary logistic regression. Results: A total of 230 mCRPC patients treated abiraterone were included. SII ≥ 535, NLR ≥ 3 and PLR ≥ 210 were considered as elevated levels (high risk groups. The median OS was 17.3 months, 21.8 months in SII < 535 group and 14.7 months in SII ≥ 535 (p < 0.0001). At univariate analysis Eastern Cooperative Oncology Group (ECOG) performance status, previous enzalutamide, visceral metastases, SII, NLR, and PLR predicted OS. In multivariate analysis, ECOG performance status, previous enzalutamide, visceral metastases, SII, and NLR remained significant predictors of OS [hazard ratio (HR) = 5.08, p < 0.0001; HR = 2.12, p = 0.009, HR = 1.77, 95% p = 0.012; HR = 1.80, p = 0.002; and HR = 1.90, p = 0.001, respectively], whereas, PLR showed a borderline ability only (HR = 1.41, p = 0.068). Conclusion: SII and NLR might represent an early and easy prognostic marker in mCRPC patients treated with abiraterone. Further studies are needed to better define their impact and role in these patients.

Lymphopenia and clinical outcome of elderly patients treated with sunitinib for metastatic renal cell cancer.

OBJECTIVE: Lymphopenia is associated with toxicity and outcomes in several cancer types. We assessed the association between pre-treatment lymphopenia, toxicity, and clinical outcomes in elderly patients with metastatic renal cell cancer (mRCC) treated with first-line sunitinib. Prognostic factors in these patients were also evaluated. PATIENTS AND METHODS: We reviewed the clinical records of 181 patients with mRCC aged ≥70 years treated with first-line sunitinib in 17 Italian Oncology Units from February 2006 to September 2011. Baseline lymphopenia was defined as lymphocyte counts <1000/µL. RESULTS: Twenty-nine (16%) patients had a baseline lymphocyte count <1000/µL (group A) and 152 (84%) patients had a lymphocyte count ≥1000/µL (group B). Although no differences between the two groups were reported in terms of overall response rate (P = 0.207), dose reductions (P = 0.740), discontinuation due to adverse events (P = 0.175) or overall incidence of grade 3-4 toxicities (P = 0.112), more patients in the lymphopenia group had grade 3-4 neutropenia (P = 0.017), grade 3-4 thrombocytopenia (P = 0.017) and grade 3-4 diarrhea (P = 0.006). In multivariate analysis, performance status and Heng score were predictors of progression-free survival (P = 0.015 and P = 0.0006, respectively), while performance status, Heng score, and lymphopenia were found to be significantly associated with overall survival (P = 0.007, P < 0.0001 and P = 0.023, respectively). CONCLUSIONS: Sunitinib appears to be safe and active in elderly patients with lymphopenia. Lymphocyte count is an independent prognostic factor for overall survival in elderly patients with mRCC treated with first-line sunitinib.

Gemcitabine combined with either pemetrexed or paclitaxel in the treatment of advanced non-small cell lung cancer: a randomized phase II SICOG trial.

PURPOSE: To estimate the safety, activity, and impact on quality of life of a combination of gemcitabine and pemetrexed in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) in the context of a randomized two-stage phase II study. PATIENTS AND METHODS: Patients in stage IIIB or IV NSCLC were randomly allocated to receive either gemcitabine 1250 mg/m(2) on day 1, and pemetrexed (Alimta) 500 mg/m(2) followed by gemcitabine 1250 mg/m(2) on day 8 of a 3-weekly cycle (GA arm), or paclitaxel 120 mg/m(2) followed by gemcitabine 1000 mg/m(2), both given on days 1 and 8 of a 3-weekly cycle (PG arm). RESULTS: 105 (GA arm, 51; PG arm, 54) eligible patients (stage IV, 32 and 30, respectively) were enrolled into this study; thereafter, accrual was stopped due to first-stage analysis. The response rate was 20% (95% confidence interval [CI], 10-33%) in the GA arm, and 32% (95% CI, 20-46%) in the PG arm. Median progression-free survival was 5.1 (95% CI, 3.7-6.5) months in the GA arm, and 8.3 (95% CI, 5.9-10.7) months in the PG arm, while median overall survival was 10.5 (95% CI 7.1-13.9), and 13.3 (95% CI 11.7-14.9) months, respectively. Severe neutropenia (36% vs 22%), and febrile neutropenia (14% vs 7%) were more common with the GA regimen, while hair loss (52% vs 16%) and any grade peripheral neuropathy (31% vs 2%) occurred more frequently with PG regimen. Other severe side effects of GA regimen were diarrhoea (10%), liver enzyme derangement (10%), and fatigue (8%). CONCLUSION: The GA regimen was tolerated and moderately active in advanced or metastatic NSCLC. However, this combination did not yield any advantage in comparison with the PG regimen, and does not deserve further evaluation.

Prognosis of screen-detected breast cancers: results of a population based study.

BACKGROUND: The reduced mortality rate from breast carcinoma among women offered screening mammography is demonstrated after 15-20 years of follow-up. However, the assessment of 5-year overall and event-free survival could represent an earlier measure of the efficacy of mammography screening program (MSP). METHODS: All cases of breast cancer diagnosed in the Province of Modena between years 1996 and 2000 in women aged 50 to 69 years, were identified through the Modena Cancer Registry (MCR). Stage of disease and treatment information were obtained from clinical records. All the events occurring up to June 30, 2003 were retrieved by experienced monitors. Five-year overall and event-free survival were the principal end-points of the study. RESULTS: During a 5-year period, 587 primary breast cancers were detected by the MSP and 471 primary breast cancers were diagnosed out of the MSP. The screen-detected breast cancers were smaller, more likely node negative, with low histological grade, low proliferative activity and positive receptors status. Furthermore, the breast cancer diagnosed through the MSP more frequently received a conservative surgery. The 5-year survival rate was 94% in the screen-detected group, versus 84% in the other group (p = 0.0001). The rate of 5-year event-free survival was 89% and 75% for the MSP participants and not participants, respectively (p = 0.0001). CONCLUSIONS: Our data confirm a favourable outcome of screen-detected breast cancers in terms of five-year overall and event-free survival, which reflect the good quality assurance parameters of the MSP. Finally, a cancer registry should be implemented in every area covered by screening programs.