Carlos Dzik

Renal Medullary Carcinoma Response to Chemotherapy: a Referral Center Experience in Brazil

Renal medullary carcinoma (RMC) is rare, accounting for less than 1% of all renal neoplasms. Case reports suggest RMC is highly aggressive, poorly responsive to chemotherapy, often metastatic at diagnosis, affects young men with sickle cell trait, and median overall survival (mOS) is less than 12 months. We report the epidemiological characteristics, treatments performed, response rate to each treatment and mOS of five patients with RMC. All patients had sickle cell trait, four were male, three had metastatic disease at diagnosis and mean age at diagnosis was 25 years. Non-metastatic patients were submitted to nephrectomy. Two patients had partial response to first line chemotherapy including cisplatin and gemcitabine. There was no response to sunitinib or second line chemo - therapy; mOS was 6 months. Due to its rarity, case series are the only evidence available to discuss the treatment for RMC. In our experience, only cisplatin and gemcitabine based regimen offered response.

Monoclonality of Asynchronous Bilateral Lymphoma of the Testis

Objectives: Lymphoma is the most frequent testicular malignancy in men over 60 years of age. Even though patients present initially with localized disease, the high incidence of bilateral involvement, synchronous or not, and early systemic dissemination are characteristic of these neoplasms. Sometimes the interval between tumor involvement of both testes is long. The question is raised whether either the patient has a predisposition to present new clones of transformed lymphocytes, or the same disease using the same pathway from a systemic reservoir infiltrates the contralateral testis.Method: Polymerase chain reaction and DNA sequencing were used to detect immunoglobulin heavy chain (IgH) rearrangement in paraffin–embedded specimens from asynchronous tumors affecting the right and left testis of a 85–year–old man with an interval period of 13 months.Results: Both tumors showed the same IgH rearrangement.Conclusions: The lymphoma affecting the left and right testis derived from the same clone. It makes a strong case that lymphoma of the testis is the first manifestation of a systemic disease and should be treated aggressively early at the beginning of the disease.

Activity and safety of sunitinib in poor risk metastatic renal cell carcinoma patients

PURPOSE To assess the activity, safety and treatment patterns of sunitinib in patients with poor-risk metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS We retrospectively reviewed the charts of poor risk patients treated with sunitinib from October 2006 to July 2013 who met the eligibility criteria. The primary endpoint was overall survival (OS). Tumor radiological response was measured according to RECIST 1.1 and adverse events (AEs) were assessed through standard criteria. RESULTS Median OS was 8.16 months (95% CI, 5.73-10.59). Of the 53 patients included in this analysis, 9 (17.0%) achieved partial response, 12 (22.6%) had stable disease. Median treatment duration was 3.30 months (95% CI: 1.96-4.63) and 26.4% of patients discontinued treatment due to toxicity. Grade 3 or higher AEs occurred in 39.6% of patients, the most common being fatigue (15.1%), neutropenia (9.5%), nausea, vomiting and diarrhea (7.5% each). DISCUSSION Sunitinib may benefit some unselected poor-risk patients, although the rates of AEs and drug discontinuation suggest a need for careful patient monitoring.

Efficacy and Safety of Docetaxel in Elderly Patients With Metastatic Castration-Resistant Prostate Cancer

Purpose Limited data are available about the tolerability and clinical outcomes of elderly patients with metastatic castration-resistant prostate cancer (mCRPC) who are treated with docetaxel. We evaluated the efficacy and safety of docetaxel as first-line chemotherapy for patients with mCRPC who were treated in our institution. Materials and Methods We retrospectively identified patients with mCRPC and a Karnosfky performance status of 60% or greater treated with docetaxel on any schedule as first-line chemotherapy between 2008 and 2013. The primary end point was a comparison of median overall survival (OS) according to age in this population. Secondary end points were comparisons of the rates of severe toxicities, prostate-specific antigen (PSA) decline of 50% or greater, and time to progression (TTP). Results were stratified by three age groups: younger than 65 years, 65 to 74 years, and 75 years or older. Results Among the 197 patients included, 68 (34%) were younger than 65 years, 85 (43%) were 65 to 74 years, and 44 (22%) were 75 years or older. The mean number of comorbidities was not different among groups (1.19 v 1.32 v 1.43; P = .54). Patients younger than 65 years received a higher cumulative dose of docetaxel (450 mg/m2 v 382 mg/m2 v 300 mg/m2; P = .004). The rates of PSA decline of 50% or greater (41% v 47% v 36.4%; P = .51) and the median TTP (5.13 v 5.13 v 4.7 months; P = .15) were comparable among all groups. The median OS was longer in the group of patients younger than age 65 years (19.6 v 12.4 v 12.3 months; P = .012). Rates of any grade 3 or higher adverse event were not different among groups (63.2% v 71.8% v 54.5%; P = .14). Conclusion Administration of docetaxel in elderly patients who had good performance status was well tolerated. Rates of PSA decline and TTP were similar to those of younger patients, but median survival was lower.

Performance status (PS) in advanced germ cell tumors (aGCT): Clinical and prognostic value of an underreported important variable.

e16537Background: Although PS is a strong marker of adverse outcomes in most metastatic solid tumors, data of PS status are lacking in GCT, especially using validated scales such as Eastern Coopera...

MP04-17 BLOOD-BASED BIOMARKERS AS PREDICTORS OF ONCOLOGIC OUTCOMES FOR NON-MUSCLE-INVASIVE UROTHELIAL BLADDER CARCINOMA

INTRODUCTION AND OBJECTIVES: Our group has previously demonstrated that blood-based tumor markers can be useful clinical outcome predictors for non-muscle invasive urothelial carcinoma of the bladder (UCB) Our aim in this study is to further evaluate the predictive value of CEA, CA 19-9 and CA 125 on disease recurrence and progression. METHODS: We prospectively included 328 consecutive patients between February 2008 and August 2014 to measure preoperative serum levels of CEA, CA 19-9 and CA 125 before first transurethral resection of the bladder (TUR). Institutional Ethical Committee approval was obtained prior to this study. Patients diagnosed with pT2 UBC were excluded (42), leaving 286 patients for analysis of recurrence or progression. After first TUR, patients were followed with routine cystoscopy, cytology and ultrasound every 6 months. All patients with non-muscle invasive (NMI) bladder cancer with high-grade disease, previous recurrence, carcinoma in situ (CIS) or T1 received induction and maintenance intravesical BCG. RESULTS: We found that CEA and CA 19-9 levels were significantly higher in patients who had either tumor recurrence and/or progression compared to those who had no UBC recurrence during follow-up (p1⁄40.02; p1⁄40.03). As we had found previously, however, CA 125 levels did not differ between the two groups (p1⁄40.42). Overall, mean CEA level was 2.1 (0.2-12.8), CA 19-9 was 17.1 (0.4-189.9) and CA 125 was 12.5 (1.2-103.9). In patients who presented tumor recurrence and/or progression, mean CEA was 5.5, mean CA 19-9 was 21.0 and CA 125 was 13.8, while in the non-recurring group, mean CEA was 3.1, mean CA 19-9 was 11.1 and CA 125 was 11.3. Mean follow-up was 4.9 years. Patients were 70.3% males (201); 63.3% (181) of patients had pTa at first TUR. Concomitant carcinoma in situ was present in 25 cases (8.7%). CONCLUSIONS: Biomarkers utilized in routine follow-up of other malignancies, such as CEA and CA 19-9, can also be included in UCB management, since it proved able to distinguish a higher risk group of patients that could be managed accordingly. Future studies may add these blood-based tumor markers to a predictive model and validated in a larger cohort. Although CA 125 was not significantly associated with oncologic outcome, further studies are required before excluding this potential biomarker in UBC.

Gene expression profile of renal cell carcinomas after neoadjuvant treatment with sunitinib: new pathways revealed

Background In renal cell carcinoma (RCC) of the clear cell type, inactivity of the VHL gene induces overexpression of HIF1 α and its targets, the tyrosine kinase receptors, promoting RCC development and progression. The discovery of tyrosine kinase inhibitors (TKIs) changed the treatment of these tumors. Other molecular pathways involved in the TKI mechanisms of action have not been described in the literature. The aim of our study was to elucidate alternative mechanisms of action of sunitinib in tumor tissue after neoadjuvant treatment of RCC. Methods The gene expression profile was accessed using microarray (Affymetrix Human Genome U133 Plus 2.0 platform) and frozen RCC tissues collected from 5 patients with locally advanced non-metastatic tumors who underwent nephrectomy after being treated with 2 cycles of neoadjuvant sunitinib. The results were compared with matched controls comprising 6 patients with no neoadjuvant intervention. Results There was underexpression of the majority of genes after sunitinib treatment. The lower expression levels of IGFBP1, CCL20, CXCL6 and FGB were confirmed by qRT-PCR in all cases. The downregulation of gene expression leads us to search for methylation as a mechanism of action of the TKI. IGFBP1 was shown to be methylated by methylation-sensitive high-resolution melting technique. Conclusions The ultimate genetic effects of sunitinib may explain its actions as an antitumor drug that apparently suppresses the expression of important genes related to cell survival, adhesion, invasion and immunomodulation. The methylation of gene promoters was shown to be part of the mechanism of action of this class of drugs.

Outcomes of sunitinib therapy in patients (pts) with metastatic renal cell carcinoma (mRCC) with poor risk features.

476 Background: Temsirolimus is perceived as the standard of care in pts with mRCC with poor risk features. However, sunitinib (Su) is commonly used in this setting. In this study, we assessed the use of Su in an unselected mRCC population. METHODS Retrospective analysis of 51 pts with mRCC and ≥ 3 poor prognosis features, as determined in the Advanced Renal Cell Carcinoma (ARCC) trial, treated with Su between January 2006 and July 2012. Primary outcome was overall survival (OS). Clinical and laboratory parameters were evaluated, as well as Su-related adverse events (AE). Median time to treatment failure (mTTF) and OS were estimated by Kaplan-Meier methods. On exploratory grounds, univariate, and multivariate analysis using Cox regression model was performed to determine possible prognostic variables. RESULTS Median age was 60 years (26-89). Most had clear cell histology (98%), 19% prior systemic treatment, and 51% prior nephrectomy. 64%, 15%, and 4% had 4, 5, and 6 adverse prognosis factors respectively. 88% had diagnosis to treatment intervals < 1 year and 45% had KPS scores of < 80. A median of 2 cycles (0-12) were administered. 63% received standard regimen of Su (50 mg/d 4 wk on/2 wk off). Reasons for discontinuation were disease progression (63%) and adverse events (21%). Most grade ≥ 3 AE were fatigue (14%), neutropenia (8%), and stomatitis (8%). 17%, 25%, and 14% developed hypothyroidism, hand-foot syndrome (HFS), and hypertension, respectively. Two therapy-related deaths were observed (one febrile neutropenia and one intracranial hemorrhage). Estimated mTTF and mOS of this cohort were 2.4 and 6.6 months, respectively. Multivariate analysis revealed that in a model adjusted for type of Su regimen, KPS, presence of brain metastasis, and occurrence of HFS, only Su-associated hypothyroidism was significantly associated with survival (respectively, odds ratio [OR] = 0.23; 95% CI = 0.07-0.68). CONCLUSIONS Pts with mRCC with poor risk features treated with Su have an OS, TTF and rates of therapy discontinuation due to AE comparable to clinical trial subsets of similar pts. Our data suggest that the development of hypothyroidism in this setting might be useful as a predictor of OS, and this finding should be further investigated.