For many years, androgen deprivation therapy (ADT) as monotherapy has been the gold standard for metastatic hormone-sensitive prostate cancer (mHSPC) treatment. Several studies have been published ...within the last decade demonstrating a significant survival advantage resulting from combining the treatment with standard ADT plus docetaxel or androgen receptor targeted therapy (ARTA) compared to ADT monotherapy. Recently published data of the PEACE-1 and ARASENS trials suggest that in the future, triple therapy might be a treatment option for patients with mHSPC.
Treatment with androgen deprivation (ADT) has for many years been a standard treatment for patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, several phase 3 randomized ...trials have completely changed the therapeutic approach for these patients. First, two phase 3 trials, CHAARTED and STAMPEDE, showed that docetaxel added to ADT improves survival of patients with mHSPC. Here we present an overview of the most important trials in this setting: STAMPEDE, LATITUDE, ARCHES, ENZAMET and TITAN in which abiraterone acetate, enzalutamide and apalutamide combined with ADT achieved significant improvement in overall survival of patients with mHSPC compared with ADT only. All three agents combined with ADT became new standard of therapy for this group of patients.
Treatment with abiraterone acetate or enzalutamide is one of the approved approaches in men with metastatic castration-resistant prostate cancer (mCRPC) in the post-docetaxel setting. However, a ...significant fraction of patients do not respond to treatment, and we aimed to determine their characteristics. From April 2015 to May 2019, 71 patients with mCRPC were treated with abiraterone acetate (N = 34) or enzalutamide (N = 37) at our institution. Resistance to treatment was defined as radiological or scintigraphic progression within 3 months, as documented at the first control. After a median follow-up of 14.9 months, resistance was detected in 22 patients (31%). Many of the baseline characteristics differed between responders and nonresponders but did not serve as predictors with clinically acceptable certainty. To overcome this, the resistance score was defined as the number of positive out of the following six predictors: Most patients with resistance and a few responders had >3 positive predictors. Therefore, by using a cutoff of four positive predictors, the resistance score showed both a high sensitivity of 82% 57-96%; 95% confidence interval (CI) and a specificity of 88% (74-96%; 95% CI). The proposed resistance score integrates the diagnostic performances of multiple predictors and may serve to decide which patients with mCRPC should be offered treatments other than hormonal therapy.
In 2011, we demonstrated that bevacizumab in combination with capecitabine as first-line treatment is effective in elderly patients with metastatic colorectal cancer (mCRC). We present the final ...results of the study with data on tumor molecular biology, sidedness and postprogression therapy. Forty patients with mCRC aged ≥70 years, initially treated with bevacizumab and capecitabine, were followed from the start of the treatment of metastatic disease to death. Tumor tissue samples were retrospectively analyzed for RAS, BRAF and microsatellite status. After a median follow-up time of 20.5 months, the median progression-free survival (PFS) and overall survival (OS) were 9.8 and 20.5 months, respectively and the objective response rate (ORR) was 65%. Twelve patients had mutation in RAS and four patients in BRAF gene, which coexisted with MSI in two cases. Patients with the right-sided tumor had apparently, but not statistically significantly lower PFS (8.6 vs. 13 months, P = 0.14) and statistically significantly lower OS (13 vs. 23.1 months, P = 0.046). Twelve patients with one or more postprogression therapy lines had significantly better ORR (12/12 = 100% vs. 14/28 = 50%, P = 0.003), median PFS (17.2 vs. 8.5 months, P < 0.001) and median OS (42 vs. 13 months, P < 0.001) than patients who received just first-line study treatment. Elderly patients with mCRC responded favorably to bevacizumab and capecitabine, especially the subgroup with the left-sided primary tumor. In the further subset of this group, characterized by RAS/BRAF wild-type and MSS tumors, the application of postprogression therapies was feasible and resulted in significant prolongation of survival.
Pazopanib is an oral multitargeting tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFRs), approved as the first-line treatment of metastatic renal cell carcinoma ...(mRCC) and soft tissue sarcoma (STS) at a fixed dose of 800 mg daily taken fasted. Potential drug-meal interactions and adverse events (AEs) may lack recognition and the related data in literature. We report one case of stomatitis/oral mucositis associated with pazopanib administrated with an oral nutritional supplement enriched with omega-3 fatty acids. The 50-year-old patient with mRCC started pazopanib treatment at standard doses of 800 mg daily as first-line therapy for mRCC, and after a few days, he developed stomatitis. Co-administration of pazopanib with high-fat meals could increase the solubility of highly lipophilic pazopanib, increasing its plasma pazopanib area under the curve (AUC), and maximum concentration (Cmax) above optimal therapeutic level can consequently lead to increased frequency/grade of AEs.
The objective of our study was to assess the real-world safety and efficacy of nivolumab in the second- or later-line treatment of metastatic renal cell carcinoma (mRCC). We conducted a multicenter, ...retrospective, observational study of real-world data from patients who were treated with nivolumab under a patient expanded access program from 2015 to 2017 in Croatia, Hungary, and Malta. The primary safety endpoint was the discontinuation of therapy because of adverse events. The primary efficacy endpoint was overall survival (OS). We collected data from 87 patients with a median (interquartile range (IQR)) age of 63 (57-68) years, and 21% were females. The median (IQR) follow-up was 11 (5-31) months. Treatment was discontinued because of toxicity in 4 (5%) patients. Four (5%) patients experienced treatment-related adverse events of grade 3 or 4. The OS was 18.0 (95% CI: 11.0 to 28.6) months, and the PFS was 8.5 (95% CI: 4.9 to 12.1) months. Our study indicated a good safety and efficacy profile of nivolumab in the second- or later-line treatment of mRCC patients in a real-world clinical practice environment, which is comparable with the findings of the registrational trial.
The relative survival of elderly patients with metastatic colorectal cancer (mCRC) is generally worse than that of younger patients because of more advanced stage at presentation, comorbidity and ...reduced use of optimal therapy. We conducted a prospective phase II trial of the combination of bevacizumab and capecitabine in elderly patients with mCRC. In total 41 patients aged more than or equal to 70 years with mCRC, who had not received chemotherapy earlier for metastatic disease, were enroled. Patients received capecitabine (1000 mg/m twice daily on days 1-14) and bevacizumab (7.5 mg/kg of body weight on day 1). The treatment cycles were repeated every 3 weeks. The overall response rate was 65%, including 13% of patients with a complete response and 53% of patients with a partial response. A further 13% of patients maintained stable disease. The median progression-free survival was 11.5 months and the median overall survival was 21.2 months. Despite the advanced age of participants, the rate of bevacizumab-related and capecitabine-related adverse events was consistent with that reported earlier in the general mCRC population. The combination of bevacizumab and capecitabine is effective and has a favourable tolerability profile and should be considered as an option for the initial treatment of mCRC in elderly patients.
Purpose
The purpose of this article is to report the outcome of neoadjuvant radiochemotherapy (N-RCT) + surgery in patients with squamous cell carcinoma of the esophagus at a single institution.
...Methods
We retrospectively reviewed data from patients who were referred to our department for N-RCT. From 1988–2011, 103 patients were treated with N-RCT with cisplatin and/or 5-fluorouracil (5-FU). Group 1: (n = 55) from 1988–2006 with 39.6–40 Gy and 5-FU with (n = 17) or without cisplatin (n = 38). Group 2: from 2003–2010 with 44–45 Gy and 5-FU with (n = 40) or without cisplatin (n = 8). All patients underwent radical resection with reconstruction according to tumor location and 2-field lymph node dissection. The degree of histomorphologic regression was defined as grade 1a (pCR, 0 % residual tumor), grade 1b (pSTR, < 10 % residual tumor), grade 2 (10–50 % residual tumor), and grade 3 (> 50 % residual tumor).
Results
Median follow-up time from the start of N-RCT was 100 months (range 2–213 months). The median overall survival (OS) for the whole cohort was 42 months and the 5-year OS was 45 ± 5 %. In the multivariate analysis, worse ECOG performance status (p < 0.001), weight loss > 10 % before the start of the N-RCT (p = 0.025), higher pT category (p = 0.001), and grade 2/3 pathologic remission (p < 0.001) were significantly associated with a poor OS. PCR and pSTR rates for group 1 were 36 % and 18 % compared to 53 % and 22 % for group 2 (p = 0.011). There was a tendency for a better outcome in group 2 patients without statistical significance. The 5-year OS, disease-free survival and recurrent-free survival were 36 ± 7 %, 35 ± 6, and 36 ± 7 % for group 1 and 55 ± 7, 49 ± 7, and 53 ± 7 in group 2 (p = 0.117, p = 0.124, and p = 0.087). There was no significant difference between the two groups considering the postoperative morbidity and mortality.
Conclusion
Higher radiation doses and more use of simultaneous cisplatin lead to higher pathologic response rates to N-RCT and may be associated with better survival outcomes. Prospective controlled trials are needed to assess the true value of intensified N-RCT regimens.
Skeletal involvement is common in patients with renal cell carcinoma (RCC): ∼30% of patients with metastatic RCC (mRCC) will develop bone metastases. Inhibition of vascular endothelial growth factor ...(VEGF) has been pursued as a therapeutic target in the treatment of metastatic clear-cell RCC (m-ccRCC). Tyrosine kinase inhibitors (TKIs), such as sunitinib, pazopanib, sorafenib, and the monoclonal antibody bevacizumab, became the therapy of choice for patients with m-ccRCC. Besides the undisputed efficacy of TKI in the treatment of m-ccRCC, the problem of metastatic bone disease still remains. There is evidence that the presence of bone metastases in m-ccRCC patients has a significant and clinically relevant negative impact on survival and potentially on the outcome of VEGF-targeted therapy. Also, a relatively common practice in the treatment of such patients is bone-directed therapy with bisphosphonates (BPs). Recent evidence shows a potentially synergistic effect on efficacy but also the potential for increased toxicity of combining TKIs and BPs. This review article highlights the importance of this subject and aims to facilitate further research and optimize the treatment of this important and common group of RCC patients.
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