Yuksel Urun

Adjuvant Chemotherapy for Invasive Bladder Cancer: A 2013 Updated Systematic Review and Meta-Analysis of Randomized Trials

CONTEXT The role of adjuvant chemotherapy remains poorly defined for the management of muscle-invasive bladder cancer (MIBC). The last meta-analysis evaluating adjuvant chemotherapy, conducted in 2005, had limited power to fully support its use. OBJECTIVE To update the current evidence of the benefit of postoperative adjuvant cisplatin-based chemotherapy compared with control (ie, surgery alone) in patients with MIBC. EVIDENCE ACQUISITION A comprehensive literature review was performed to identify all randomized controlled trials (RCTs) comparing adjuvant cisplatin-based chemotherapy with control for patients with MIBC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to May 2013. An updated systematic review and meta-analysis was performed. EVIDENCE SYNTHESIS A total of 945 patients included in nine RCTs (five previously analyzed, one updated, and three new) were examined. For overall survival, the pooled hazard ratio (HR) across all nine trials was 0.77 (95% confidence interval [CI], 0.59-0.99; p=0.049). For disease-free survival, the pooled HR across seven trials reporting this outcome was 0.66 (95% CI, 0.45-0.91; p=0.014). This disease-free survival benefit was more apparent among those with positive nodal involvement (p=0.010). CONCLUSIONS This updated and improved meta-analysis of randomized trials provides further evidence of an overall survival and disease-free survival benefit in patients with MIBC receiving adjuvant cisplatin-based chemotherapy after radical cystectomy.

Cytoreductive nephrectomy in patients with metastatic non-clear-cell renal cell carcinoma (RCC).

To determine whether patients with metastatic non‐clear‐cell renal cell carcinoma (RCC) benefit from cytoreductive nephrectomy (CN).

Comparison of ICE (Ifosfamide-Carboplatin-Etoposide) Versus DHAP (Cytosine Arabinoside-Cisplatin-Dexamethasone) as Salvage Chemotherapy in Patients with Relapsed or Refractory Lymphoma

Background: High dose chemotherapy with autologous stem cell transplantation is currently the treatment of choice for relapsed or refractory lymphoma patients. However, its applicability is mostly restricted to patients responding to salvage chemotherapy. Optimal salvage regimen for these patients is unclear. In this study, our aim was to compare the efficacy and toxicity profiles of DHAP (cytosine arabinoside, cisplatin and dexamethasone) and ICE (ifosfamide, carboplatin and etoposide) regimens in the salvage treatment of relapsed and refractory lymphoma. Patients and Methods: In this retrospective analysis, 53 patients with primary refractory or relapsed Hodgkins disease (HD) (n = 13) or non-Hodgkin lymphoma (NHL) (n = 40) who received ICE or DHAP salvage regimen were included. Results: Of 53 patients, 21 (39,6%) were female and the median age was 43 years. A total of 73 courses of ICE and 59 courses of DHAP were administered. Response could be evaluated in 49 patients (36 NHL and 13 HD). Of 49 patients, 11 (22.5%) achieved complete remission (CR) and 17 (35%) achieved partial remission (PR), leading to an overall response rate (ORR: CR + PR) of 57.5%. In the evaluable ICE group (n = 22) rates of CR, PR, and ORR were 27%, 41% and 68% and in the DHAP group (n = 27) rates of CR, PR, and ORR were 18%, 30% and 48% (p = 0.24, for ORR). Toxicity with both regimens was within acceptable limits. The major grade III–IV toxicities for both groups were hematological (neutopenia and thrombocytopenia). The main non-hematological toxicity was renal and observed in 8 patients. Conclusion: Although the toxicity profiles of both ICE and DHAP regimens were similar in the treatment of patients with relapsed or refractory HD or NHL, ICE seems to have higher rates of response than DHAP regimen does.

Association of ABO blood group and risk of lung cancer in a multicenter study in Turkey.

BACKGROUND The ABO blood groups and Rh factor may affect the risk of lung cancer. MATERIALS AND METHODS We analyzed 2,044 lung cancer patients with serologically confirmed ABO/Rh blood group. A group of 3,022,883 healthy blood donors of Turkish Red Crescent was identified as a control group. We compared the distributions of ABO/Rh blood group between them. RESULTS The median age was 62 years (range: 17-90). There was a clear male predominance (84% vs. 16%). Overall distributions of ABO blood groups were significantly different between patients and controls (p=0.01). There were also significant differences between patients and controls with respect to Rh positive vs. Rh negative (p=0.04) and O vs. non-O (p=0.002). There were no statistically significant differences of blood groups with respect to sex, age, or histology. CONCLUSIONS In the study population, ABO blood types were associated with the lung cancer. Having non-O blood type and Rh-negative feature increased the risk of lung cancer. However, further prospective studies are necessary to define the mechanisms by which ABO blood type may influence the lung cancer risk.

Clinicopathological Features of Patients with Malignant Mesothelioma in a Multicenter, Case-Control Study: No Role for ABO-Rh Blood Groups

BACKGROUND Malignant mesothelioma (MM) is an aggressive tumor of mesothelial surfaces. Previous studies have observed an association between ABO blood groups and risk of certain malignancies, including pancreatic and gastric cancer; however, no information on any association with MM risk is available. The aim of this study was to investigate possible associations amoong MM clinicopathological features and ABO blood groups and Rh factor. MATERIALS AND METHODS In 252 patients with MM, the ABO blood group and Rh factor were examined and compared with the control group of 3,022,883 healthy volunteer blood donors of Turkish Red Crescent between 2004 and 2011. The relationship of blood groups with various clinicopathological features were also evaluated in the patient group. RESULTS The median age was 55 (range: 27-86) and 61.5% of patients were male. While 82.8% of patients had a history of exposure to asbestos, 60.7% of patients had a smoking history. Epithelioid (65.1%) was the most common histology and 18.7% of patients had mixed histology. Overall, the ABO blood group distribution of the 252 patients with MM was comparable with the general population. The median overall survival (OS) was 14 months (95% confidence interval, 11.3-16.6 months). The median OS for A, B, AB, and O were 11, 15, 16, and 15 months respectively (p=0.396). First line chemotherapy was administered to 118 patients. The median OS of patients on pemetrexed or gemcitabine was longer than patient who was not administered chemotherapy [17 months (95%CI, 11.7-22.2) vs. 9 months (95%CI, 6.9-11.0); p<0.001]. CONCLUSIONS The results of this study suggest that patients with MM can benefit from treatment with pemetrexed or gemcitabine in combination with cisplatin. We did not observe a statistically significant association between ABO blood group and risk of MM.

Predictors of outcome in patients with advanced nonseminomatous germ cell testicular tumors.

Background: Predictor factors determining complete response to treatment are still not clearly defined. We aimed to evaluate clinicopathological features, risk factors, treatment responses, and survival analysis of patient with advanced nonseminomatous GCTs (NSGCTs). Materials and Methods: Between November 1999 and September 2011, 140 patients with stage II and III NSGCTs were referred to our institutions and 125 patients with complete clinical data were included in this retrospective study. Four cycles of BEP regimen were applied as a first-line treatment. Salvage chemotherapy and/or high-dose chemotherapy (HDCT) with autologous stem cell transplantation were given in patients who progressed after BEP chemotherapy. Post-chemotherapy surgery was performed in selected patients with incomplete radiographic response and normal tumor markers. Results: The median age was 28 years. For the good, intermediate and poor risk groups, compete response rates (CRR) were, 84.6%, 67.9% and 59.4%, respectively. Extragonadal tumors, stage 3 disease, intermediate and poor risk factors, rete testis invasion were associated with worse outcomes. There were 32 patients (25.6%) with non-CR who were treated with salvage treatment. Thirty-one patients died from GCTs and 94% of them had stage III disease. Conclusions: Even though response rates are high, some patients with GCTs still need salvage treatment and cure cannot be achieved. Non-complete response to platinium-based first-line treatment is a negative prognostic factor. Our study confirmed the need for a prognostic and predictive model and more effective salvage approaches.

ERCC1 as a prognostic factor for survival in patients with advanced urothelial cancer treated with platinum based chemotherapy: A systematic review and meta-analysis

BACKGROUND The predictive role of excision repair cross-complementing group 1 (ERCC1) as a predictive factor in patients with advanced urothelial cancer (AUC) treated with platinum-based treatment is not well defined. Here, we evaluate the role of ERCC1 in patients with AUC treated with platinum-based treatment. METHODS We performed comprehensive, systematic computerized search to identify relevant studies through Medline, Embase, Cochrane Controlled Trials Register (CCTR) databases and abstracts from American Society of Clinical Oncology (ASCO) and ASCO Genitourinary Cancers Symposium, European Society For Medical Oncology (ESMO) and European Association of Urology (EAU) meeting up to July 2015. A systematic review and meta-analysis were performed. RESULTS We included a total of 1475 patients from 13 studies. We found that ERCC1 positivity was significantly associated with worse progression-free survival (pooled HR: 1.54, 95% CI: 1.13-2.11, p=0.006). There was no significant association with overall survival (pooled HR1.63, 95% CI: 0.93-2.88, p=0.09) and disease-free survival (pooled HR: 1.092, 95% CI: 0.63-1.90, p=0.75). CONCLUSION ERCC1 positivity might be a prognostic indicator for poorer survival outcomes among patients with AUC. ERCC1 positivity was trending to poorer OS but was statistically worse for PFS. Further large prospective studies are warranted as ERCC1 could be used as a predictive marker to direct treatment of patients with AUC.

Pharmacogenomic Markers of Targeted Therapy Toxicity in Patients with Metastatic Renal Cell Carcinoma

BACKGROUND Targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) may be associated with a high rate of toxicity that undermines treatment efficacy and patient quality of life. Polymorphisms in genes involved in the pharmacokinetic pathways of TTs may predict toxicity. OBJECTIVE To investigate whether selected single-nucleotide polymorphisms (SNPs) in three core genes involved in the metabolism and transport of sunitinib and the mTOR inhibitors everolimus and temsirolimus are associated with adverse events (AEs). DESIGN, SETTING, AND PARTICIPANTS Germline DNA was extracted from blood or normal kidney tissue from mRCC patients of Caucasian ethnicity in two cohorts treated with either sunitinib (n=159) or mTOR inhibitors (n=62). Six SNPs in three candidate genes (CYP3A4: rs2242480, rs4646437, and rs2246709; CYP3A5: rs15524; and ABCB1: rs2032582 and rs1045642) were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary endpoints were grade ≥3 AEs for all patients; grade ≥3 hypertension in the sunitinib cohort, and any grade pneumonitis in the mTOR inhibitors cohort. A logistic regression model was used to assess the association between SNPs and AEs, with adjustment for relevant clinical factors. RESULTS AND LIMITATIONS In total, 221 samples were successfully genotyped for the selected SNPs. In the sunitinib cohort, the CYP3A4 rs464637 AG variant was associated with a lower risk of high-grade AEs (odds ratio 0.27, 95% confidence interval 0.08-0.88; p=0.03), but no SNPs were associated with hypertension. In the mTOR inhibitor cohort, none of the selected SNPs was associated with analyzed toxicities. CONCLUSIONS We observed an association between CYP3A4 polymorphisms and toxicity outcomes in mRCC patients treated with sunitinib, but not with everolimus or temsirolimus. Our findings are exploratory in nature, and further validation in independent and larger cohorts is needed. PATIENT SUMMARY We found that variants of CYP3A4, a gene involved in drug metabolism, are associated with sunitinib toxicity. This information may help in better selection of patients for targeted therapies in metastatic renal cell carcinoma.

ABO blood group alleles and prostate cancer risk: Results from the breast and prostate cancer cohort consortium (BPC3).

ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney, and skin, but has not been evaluated in relation to risk of aggressive prostate cancer.

How Shall We Name the Chemotherapy Administration Before and After Metastasectomy? How About “M-Neoadjuvant” and “M-Adjuvant”?

Correct and universal terminology to define disease processes or therapies in medicine is an invaluable tool for precise communication among physicians and researchers. Medical oncology, as a quickly developing discipline in every aspects, crucially needs new terminologies. Systemic chemotherapy administration is categorized into several groups such as neoadjuvant, adjuvant, and palliative. In the ‘‘neoadjuvant’’ category, in addition to targeting micrometastatic malignant cells, the intent is usually to shrink a locally advanced tumor enough to be surgically removed. In the ‘‘adjuvant’’ category, our only aim is to eradicate micrometastatic tumor cells after the primary tumor is removed. In the ‘‘metastatic’’ category, the intent is to control malignancy, which is radiologically detectable, for extending survival or symptomatic palliation. However, not every clinical scenario fits into these criteria. The latest developments in surgery and chemotherapy have enabled us to prolong the survival of, and even cure, patients via metastasectomy and chemotherapy, even though they have ‘‘metastatic’’ disease.. The clinical scenario after surgery in patients without detectable cancer by imaging is called ‘‘no evidence of disease’’ (NED). The systemic chemotherapy administered in this setting does not fit into any of the categorizations defined above. Should we call it ‘‘adjuvant’’? But the patient has metastatic disease even though the condition is NED. Should we call it ‘‘metastatic’’? But the patient has no overt disease by imaging. There is a crucial need for a new term to categorize the chemotherapy administration in the NED setting because neither the term ‘‘adjuvant’’ nor the term ‘‘metastatic’’ precisely cover it. We suggest the terms ‘‘m-neoadjuvant’’ and ‘‘m-adjuvant’’ for neoadjuvant and adjuvant administration in potential NED cases before and NED disease after metastasectomy, respectively. The ‘‘m’’ here stands for ‘‘metastatic.’’