Differences in the approaches of cancer specialists toward adolescent and young adult cancer care.

BACKGROUND: This study investigated the medical care of adolescent and young adult (AYA) cancer patients and compared approaches toward AYA cancer care by pediatric and adult cancer specialists. METHODS: An Internet survey was conducted among 1,305 specialists (192 pediatric and 1,109 adult) in 2016. RESULTS: The rate of awareness of the term "AYA" was lower for adult specialists than for pediatric specialists. The departments that are responsible for caring for AYA cancer patients change when they reach 20 years of age. For the treatment of AYA patients, both pediatric and adult specialists preferred a multidisciplinary team as a top priority issue. A special ward or hospital rooms for AYA was required mostly for AYA patients under 24, and the needs for special wards or rooms for AYA was higher in pediatric specialists than in adult specialists. However, for AYA patients over 25, about 60% of adult specialists and 35% of pediatric specialists believed that no special care was required. As for desirable follow-up protocols for pediatric cancer AYA survivors, half of the specialists considered that they should be conducted mainly by pediatric specialists in cooperation with adult specialists, and 30% to 40% of the specialists considered that transition to the corresponding adult medicine department would be preferable. CONCLUSIONS: There were obvious differences in medical care and support for AYA cancer patients according to their age, particularly under the age of 20 or 24, and according to whether the onset of disease occurred during the AYA period or whether it was secondary to pediatric cancers. For each aspect, appropriate programs would require close cooperation between pediatric and adult specialists.

Clinical significance of programmed death-1 and programmed death-ligand 1 expression in the tumor microenvironment of clear cell renal cell carcinoma.

Recently, immunotherapy based on blocking immune checkpoints with programmed death-1 (PD-1) or PD-ligand 1 (PD-L1) Abs has been introduced for the treatment of advanced clear cell renal cell carcinoma (ccRCC), especially tumors resistant to vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs), but the significance of their expression in the tumor microenvironment is unclear. We investigated these immune checkpoint markers in tumor cells and tumor-infiltrating immune cells (TIIC) in the tumor microenvironment of 100 untreated and 25 VEGF-TKI-treated primary ccRCC tissues. Upregulated expression of PD-1 and PD-L1 by TIIC, and PD-L1 by tumor cells was associated with the histological grade and unfavorable prognosis of RCC patients. High PD-1 and PD-L1 expression by TIIC was associated with a poorer response to VEGF-TKI, whereas PD-L1 expression by tumor cells did not affect the efficacy of the treatment. Furthermore, increased PD-1-positive TIIC and PD-L1-positive TIIC were observed in tumors treated with VEGF-TKIs compared with those in untreated tumors. Our data suggest that PD-1 and PD-L1 expression by TIIC in the tumor microenvironment is involved in treatment resistance, and that sequential therapy with immune checkpoint inhibitors could be a promising therapeutic strategy for ccRCC resistant to VEGF-TKI treatment.

Correction to: Current situation of cancer among adolescents and young adults in Japan.

In the original publication, Tables 4 and 5 have not been published in a readable format. The corrected clear version is given in this Correction.

NCCN Asia Consensus Statement prostate cancer.

The National Comprehensive Cancer Network, an NPO organization comprised of university hospitals and cancer centers in the US. The publication of clinical practice guidelines on the treatment, diagnosis, prevention and screening is one of important activities. Background factors of prostate cancer patients, such as the prevalence, age at the diagnosis and mortality are markedly different between Western countries and Asia. Thus, various factors should be taken into consideration at the treatment choice for individual patients. Experts from Asian countries were published as the Asia Consensus Statement. In this review, we explain important points of the Asia Consensus Statement such as differences in the epidemiological backgrounds of patients, differences in treatment options and differences in medical insurance systems.

Clinical Outcomes in Patients With Metastatic Papillary Renal-Cell Carcinoma: A Multi-Institutional Study in Japan.

BACKGROUND: Standard treatments have not been established in metastatic papillary renal-cell carcinoma (PRCC). We aimed to investigate treatment outcomes in patients with mPRCC. PATIENTS AND METHODS: This study included 51 patients who were diagnosed with PRCC at 14 institutions. Pathologic slides were reviewed by pathologists. The associations between clinical factors and overall survival (OS) were analyzed. RESULTS: Final pathologic diagnoses could be determined in 50 patients. Thirty-five tumors were diagnosed as PRCC (type 2 PRCC, 91.4%), and 15 were diagnosed as other histologic types. Targeted therapies (TTs) were provided to 25 mPRCC patients. Patients treated with TT survived significantly longer than those treated before the era of TT (median OS, 22.5 vs. 6.3 months; P = .0035). Median OS of patients who experienced stable disease for ≥ 9 months using single TT was 43.1 months. Patients treated with a tyrosine kinase inhibitor (TKI) as first-line TT survived longer after TT initiation than those treated with an mTOR inhibitor (median, 22.4 vs. 11.7 months; P = .2684). Patients treated with TKIs in both first- and second-line settings had significantly better survival after TT initiation than those treated with a TKI in one therapy line and an mTOR inhibitor in the other (31.4 vs. 12.9 months, P = .0172). Patients treated with a TKI as second-line TT survived significantly longer after second-line TT initiation than did those treated with an mTOR inhibitor (16.2 vs. 7.4 months, P = .0016). CONCLUSION: Prognoses of patients with mPRCC were improved by TT, and TKIs appeared to be the treatment of choice in both the first- and second-line settings.

Current situation of cancer among adolescents and young adults in Japan.

BACKGROUND: Cancer is rare among adolescents and young adults (AYA). Affected persons need generation-specific attention and care; however, no nationwide study has investigated the medical care structure for AYA cancer treatment in Japan. METHODS: We conducted a nationwide survey of AYA cancer for frequency of AYA patients, type of cancer, medical facilities, and certified cancer professionals. Data were collected from 14,713 patients at 218 Core Cancer Treatment Hospitals. RESULTS: The average proportion of AYA cancer patients to all cancer patients was 3.6%. The median number of patients aged 15 to 24 years per hospital was small (n = 5, range 1-51). The most frequent primary site of AYA cancer was the cervix uteri, but when cancer in situ was excluded, the hematopoietic malignancies were the most frequent cancer in males and females aged 15-24 years. In the age group 25-39 years, testicular and breast cancers were the most frequent cancers in males and females, respectively. Certified cancer professionals and facilities are necessary for appropriate care of AYA cancer patients, but the availability of such professionals varied greatly among hospitals. Hospitals with few AYA cancer patients were less likely to employ such physicians. CONCLUSIONS: The present findings suggest that medical care for AYA cancer in Japan requires further refinement and a multidisciplinary approach.

Clinical evaluation of two consecutive UroVysion fluorescence in situ hybridization tests to detect intravesical recurrence of bladder cancer: a prospective blinded comparative study in Japan.

BACKGROUND: We evaluated the use of UroVysion fluorescence in situ hybridization tests to detect the intravesical recurrence of bladder cancer during follow-up after a transurethral resection of bladder tumor (TURBT). METHODS: In this prospective, blinded, comparative study, 486 patients treated by TURBT within the prior 2 years were registered at 12 centers. Urine cytology and UroVysion tests were performed once or twice at a central testing laboratory. For the patients with no suspicious findings of bladder cancer in the first analysis, the same examination set was repeated 3 months later as the second analysis. Totals of 468 and 399 patients were eligible for the first and second analyses, respectively. We determined the sensitivity and specificity of two consecutive UroVysion tests. RESULTS: Bladder cancers were identified in 44 patients at the first analysis. The UroVysion test had 50.0% (95% CI 35.2-64.8%) sensitivity and 72.4% (68.3-76.8%). Urine cytology had 4.5% (0.0-10.7%) sensitivity and 99.8% (99.3-100.0%) specificity. The concordant rate of the first and second UroVysion test results was 72% (kappa coefficient 0.157). Interestingly, the patients with two consecutive positive UroVysion test results had the highest cancer detection rate (14.8%), which is greater than those of the patients with a positive result in either (7.2%) or neither (1.2%) of the two tests at the 3-month follow-up. CONCLUSIONS: The UroVysion test provided higher sensitivity than urine cytology to detect bladder cancer during post-TURBT follow-up. Two consecutive UroVysion tests might be a better indicator to predict intravesical recurrence.

[Current Status of Oncofertility in Adolescent and Young Adult (AYA) Generation Cancer Patients in Japan - National Survey of Oncologists].

A national survey conducted in 2016 aimed to evaluate the current status and needs of the field of oncofertility and to consider optimized medical delivery systems. A total of 739 oncologists, excluding gynecological and urological specialists, were surveyed. Of these, 99.2% thought that providing information on fertility preservation was important. Of the surveyed oncologists, 48% were affiliated with facilities providing assisted reproductive technology, and 79.3% practiced in university hospitals. Of 238 (32.2%) specialists who provided information on the risk of reproductive damage resulting from treatment in their facility, 163 (44.9%) and 75 (19.9%) practiced in university hospitals (n=363) and non-university hospitals (n= 376), respectively. In contrast, 14.3% and 32.7% of oncologists who practiced in university hospitals and non-university hospitals, respectively, collaborated with local obstetricians and gynecologists. Among oncologists who use a gradually expanding regional oncofertility network, 0.6% practice in university hospitals and 2.7% practice in non-university hospitals. Patients were advised that the risk of infertility was 92.3% and the likelihood of fertility preservation was 66.9%. Furthermore, as an ideal way of providing information on preservation of fertility, 22.9% of oncologists collaborate with local gynecologists, and 26.3% do so at a public cancer and reproductive medical counseling center. In addition, 34.7% and 55.1% of oncologists at university and non-university hospitals, respectively, thought that implementation of a fertility preservation program at a public facility would be desirable. Although most oncologists recognize the importance of providing information on reproductive medicine, the support system for reproductive function and fertility in adolescent and young adult (AYA) generation cancer patients is limited because of the lack of agreement on patient referral. The limited number of referrals in turn limits data collection in the field of oncofertility. Grant: A Health and Labour Sciences Research Grant: H27-Cancer Control-Ippan.

Oral 5-aminolevulinic acid-mediated photodynamic diagnosis using fluorescence cystoscopy for non-muscle-invasive bladder cancer: A multicenter phase III study.

OBJECTIVE: To confirm the reproducibility of the effectiveness and safety in photodynamic diagnosis of non-muscle-invasive bladder cancer using 5-aminolevulinic acid in a prospective multicenter non-randomized phase III trial. METHODS: A total of 61 patients with primary or recurrent non-muscle-invasive bladder cancer were prospectively enrolled from five hospitals between May 2015 and March 2016. 5-Aminolevulinic acid (20 mg/kg) was orally administered 3 h before transurethral resection of bladder tumors using white light or fluorescent light. Of 60 evaluable patients, 511 specimens were obtained from tumor-suspicious lesions and normal-looking mucosa. The primary end-point was sensitivity. The secondary end-points were specificity, positive and negative predictive values, and safety. RESULTS: The sensitivity of the fluorescent light source (79.6%) was significantly higher (P < 0.001) than that of the white light source (54.1%). In total, 25.4% (46/181) of tumor specimens were diagnosed as positive with only the fluorescent light source. In nine (15%) of 60 patients, the risk classification and recommended treatment after transurethral resection of bladder tumors were changed depending on the additional types of tumor diagnosed by the fluorescent light source. The specificity of the fluorescent light versus white light source was 80.6% versus 95.5%. No grade 4-5 adverse event was noted. Hypotension and urticaria were severe adverse events whose relationship to oral 5-aminolevulinic acid could not be excluded. CONCLUSIONS: These findings confirm the diagnostic efficacy and safety of photodynamic diagnosis with 20 mg/kg of oral 5-aminolevulinic acid, and show that transurethral resection of bladder tumors with a fluorescent light source using oral 5-aminolevulinic acid is well tolerated.

Efficacy and safety of 3-month dosing regimen of degarelix in Japanese subjects with prostate cancer: A phase III study.

Non-inferiority in the cumulative castration rate of the 3-month formulation of degarelix compared with the 3-month formulation of goserelin was evaluated in subjects with prostate cancer. A phase III, open-label, parallel-arm study was carried out. An initial dose of 240 mg degarelix or 3.6 mg goserelin was given s.c.; after day 28, a maintenance dose of 480 mg degarelix or 10.8 mg goserelin was given once every 84 days. Non-inferiority in castration rate and safety of degarelix to goserelin were evaluated. The primary end-point was the cumulative castration rate from day 28 to day 364 and the non-inferiority margin was set to be 10%. A total of 234 subjects with prostate cancer were randomized to the degarelix group (n = 117) and the goserelin group (n = 117). The cumulative castration rate was 95.1% in the degarelix group and 100.0% in the goserelin group. As there were no events in the goserelin group, an additional analysis was carried out using 95% confidence intervals of the difference in the proportion of subjects with castration. Analyses indicated the non-inferiority of the 3-month formulation of degarelix to goserelin. Degarelix showed more rapid decreases in testosterone, luteinizing hormone, follicle stimulating hormone, and prostate-specific antigen levels compared with goserelin. The most common adverse events in the degarelix group were injection site reactions. Non-inferiority of the 3-month formulation of degarelix to goserelin was shown for testosterone suppression. The 3-month formulation of degarelix was also found to be tolerated as an androgen deprivation therapy for patients with prostate cancer. This trial was registered with ClinicalTrials.gov (identifier NCT01964170).

Isosamidin, an extract of Peucedanum japonicum, inhibits phenylephrine-mediated contractions of the human prostate in vitro.

Isosamidin is a pharmacologically active compound extracted from Peucedanum japonicum which is used as a health food in East Asia. Our preliminary animal data suggested that isosamidin may have sufficient potency to treat patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia or overactive bladder. However, the efficacy of isosamidin in humans is unknown. Here, we examined whether isosamidin inhibits agonist-stimulated contractions in isolated human bladder and prostate tissue strips in vitro. Human bladder and prostate strips obtained from 9 to 10 male patients, respectively, were suspended in organ baths. After administration of isosamidin (10, 30, and 100 µM), concentration-response curves to agonists (acetylcholine or phenylephrine) were constructed by cumulatively increasing agonist concentration. Isosamidin inhibited phenylephrine-stimulated contractions of isolated human prostate tissue strips in a concentration-dependent manner, with significant differences observed between control and 100 µM isosamidin. In contrast, isosamidin had no effect on acetylcholine-stimulated contractions of isolated human bladder tissue strips. Isosamidin may have pharmacological potency in the treatment of male patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Clinical studies are needed to confirm the efficacy and safety of isosamidin in humans.

The Inverse Association between the Baseline Renal Function and Overall Survival in Patients with Metastatic Renal Cell Carcinoma Treated with Molecular-Targeted Agents.

BACKGROUND: The objective of this study was to investigate the prognostic significance of the baseline renal function in metastatic renal cell carcinoma (mRCC) patients treated with molecular-targeted agents. PATIENTS AND METHODS: This study included 408 consecutive mRCC patients receiving molecular-targeted therapy, consisting of 124 patients in group A and 284 patients in group B who had baseline estimated glomerular filtration rates ≥ 60 ml/min/1.73 m2 and < 60 ml/min/1.73 m2, respectively. RESULTS: Compared with group A, group B was significantly less likely to have poor prognostic factors, such as a high proportion of patients without nephrectomy. The median overall survivals (OSs) after the initiation of targeted therapy in groups A and B were 21.4 and 35.8 months, respectively, and there was a significant difference in the OS between the 2 groups. However, multivariate analysis showed a lack of independent impact of the baseline renal function on the OS. Furthermore, when patients without a nephrectomy were excluded, no significant difference was noted in the OS between the 2 groups. CONCLUSION: These findings suggested that there was no adverse impact of an unfavorable baseline renal function on the efficacy of targeted agents against mRCC. Thus, molecular-targeted therapy should not be avoided in mRCC patients with an impaired baseline renal function.

Report of the Second Asian Prostate Cancer (A-CaP) Study Meeting.

The Asian Prostate Cancer (A-CaP) Study is an Asia-wide initiative that has been developed over the course of 2 years. The study was launched in December 2015 in Tokyo, Japan, and the participating countries and regions engaged in preparations for the study during the course of 2016, including patient registration and creation of databases for the purpose of the study. The Second A-CaP Meeting was held on September 8, 2016 in Seoul, Korea, with the participation of members and collaborators from 12 countries and regions. Under the study, each participating country or region will begin registration of newly diagnosed prostate cancer patients and conduct prognostic investigations. From the data gathered, common research themes will be identified, such as comparisons among Asian countries of background factors in newly diagnosed prostate cancer patients. This is the first Asia-wide study of prostate cancer and has developed from single country research efforts in this field, including in Japan and Korea. At the Second Meeting, participating countries and regions discussed the status of preparations and discussed various issues that are being faced. These issues include technical challenges in creating databases, promoting participation in each country or region, clarifying issues relating to data input, addressing institutional issues such as institutional review board requirements, and the need for dedicated data managers. The meeting was positioned as an opportunity to share information and address outstanding issues prior to the initiation of the study. In addition to A-CaP-specific discussions, a series of special lectures was also delivered as a means of providing international perspectives on the latest developments in prostate cancer and the use of databases and registration studies around the world.

Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup analysis from the CheckMate 025 study.

BACKGROUND: Nivolumab improved overall survival (OS) and objective response rate (ORR) versus everolimus in previously treated patients with advanced renal cell carcinoma in the phase III CheckMate 025 study (minimum follow-up: 14 months). We report efficacy and safety in the global and Japanese populations (minimum follow-up: 26 months). METHODS: Patients were randomized 1:1 to receive nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10-mg tablet orally once daily. Primary endpoint: OS, key secondary endpoints: ORR, progression-free survival and safety. RESULTS: Of 410 (nivolumab) and 411 (everolimus) patients, 37 (9%) and 26 (6%), respectively, were Japanese. Median OS for the global population was 26.0 months (nivolumab) and 19.7 months (everolimus; hazard ratio 0.73 [95% confidence interval [CI]: 0.61-0.88]; P = 0.0006), with medians not reached for Japanese patients. ORR for the global population was 26% (nivolumab) versus 5% (everolimus; odds ratio 6.13; 95% CI: 3.77-9.95); ORR for Japanese patients: 43% versus 8% (odds ratio 9.14; 95% CI: 1.76-88.33). In Japanese patients, any-grade treatment-related adverse events (AEs) occurred in 78% (Grade 3-4, 19%; most common, anemia [5%]) treated with nivolumab and 100% (Grade 3-4, 58%; most common, hypertriglyceridemia [12%]) treated with everolimus; the most common with nivolumab was diarrhea (19%) and with everolimus was stomatitis (77%). Quality of life was stable in the nivolumab arm. CONCLUSIONS: With >2 years of follow-up, Japanese patients had a higher response rate with nivolumab versus everolimus that was more pronounced yet consistent with the global population, with median OS not reached, and a favorable safety profile.

[Evaluation of CT-Guided Percutaneous Needle Biopsy for Diagnosis of Renal Tumor].

We performed computed tomographic (CT)-guided percutaneous needle biopsy for renal tumors that were difficult to diagnose or were inoperable malignant renal tumors. Nineteen patients who underwent CT-guided percutaneous needle biopsy between November 2007 and March 2015 at Hamamatsu University Hospital were included in this study. The median tumor diameter was 78 mm (40-140 mm). Seventeen patients were diagnosed pathologically by biopsy, but 2 patients could not be diagnosed despite the existence of adequate sample volume. One patient had an adverse complication ; fever (CTCAE ver 4.0 grade 1). The median duration of follow-up was 21 months (0-111 months), no one had tumor seeding along a needle tract. CT-guided percutaneous needle biopsy of renal tumors is helpful for pathological diagnosis and further treatment planning. However, there are still some limitations to obtain an accurate diagnosis.

Comparison of Tyrosine Kinase Inhibitor Versus Mammalian Target of Rapamycin Inhibitor as Second-line Molecular-targeted Therapy for Patients with Poor-risk Metastatic Renal Cell Carcinoma.

AIM: The objective of this study was to compare the efficacies of tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin inhibitor (mTORI) as second-line molecular-targeted therapy in patients with poor-risk metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: This study included 89 consecutive patients with mRCC who were classified into a poor-risk group after the failure of first-line molecular-targeted agent and subsequently received second-line targeted therapy. RESULTS: Of the 89 patients, 59 and 30 were treated with TKI and mTORI, respectively, as second-line targeted therapy, and no significant differences in the clinicopathological characteristics were noted between the TKI and mTORI groups. There was no significant difference in the response rate to the second-line agent between the TKI and mTORI groups; however, the proportion of patients with tumor shrinkage in the TKI group was significantly higher than that in the mTORI group. There was no significant difference in the progression-free survival between the TKI and mTORI groups, while the overall survival for the TKI group was significantly superior to that of the mTORI group (median of 15.0 vs. 7.6 months, respectively). Furthermore, the type of second-line agent (i.e. TKI vs. mTORI) was identified as an independent predictor of the OS, but not of PFS. CONCLUSION: Favorable disease control might be achieved by introducing TKI as second-line targeted therapy for patients with poor-risk mRCC.

Functional analysis of fatty acid binding protein 7 and its effect on fatty acid of renal cell carcinoma cell lines.

BACKGROUND: Renal cell carcinomas (RCCs) overexpress fatty acid binding protein 7 (FABP7). We chose to study the TUHR14TKB cell line, because it expresses higher levels of FABP7 than other cell lines derived from renal carcinomas (OS-RC-2, 786-O, 769-P, Caki-1, and ACHN). METHODS: FABP7 expression was detected using western blotting and real-time PCR. Cell proliferation was determined using an MTS assay and by directly by counting cells. The cell cycle was assayed using flow cytometry. Cell migration was assayed using wound-healing assays. An FABP7 expression vector was used to transfect RCC cell lines. RESULTS: The levels of FABP7 expressed by TUHR14TKB cells and their doubling times decreased during passage. High-passage TUHR14TKB cells comprised fewer G0/G1-phase and more S-phase cells than low-passage cells. Cell proliferation differed among subclones isolated from cultures of low-passage TUHR14TKB cells. The proliferation of TUHR14TKB cells decreased when FABP7 was overexpressed, and the cell migration property of TUHR14TKB cells were decreased when FABP7 was overexpressed. High concentrations of docosatetraenoic acid and eicosapentaenoic acid accumulated in TUHR14TKB cells that overexpressed FABP7, and docosatetraenoic acid enhanced cell proliferation. CONCLUSIONS: The TUHR14TKB cell line represents a heterogeneous population that does not express FABP7 when it rapidly proliferates. The differences in FABP7 function between RCC cell lines suggests that FABP7 affects cell proliferation depending on cell phenotype.

Efficacy and safety of a 3-month dosing regimen of degarelix in Japanese patients with prostate cancer: a phase II maintenance-dose-finding study.

OBJECTIVE: To evaluate the efficacy and safety of degarelix 3-month depot in Japanese patients with prostate cancer. METHODS: In this Phase II, open-label, parallel-group study, 155 Japanese prostate cancer patients were randomized to treatment with degarelix administered subcutaneously at a maintenance dose of 360 or 480 mg every 84 days for 12 months, after receiving an initial dose of 240 mg. The primary endpoint was the cumulative probability of serum testosterone ≤0.5 ng/ml (Days 28-364). Secondary endpoints included percent change in serum prostate-specific antigen level and proportion of patients with prostate-specific antigen failure at Day 364. For safety, adverse events were evaluated. RESULTS: The cumulative probability of serum testosterone ≤0.5 ng/ml (Days 28-364) was 88.3% (95% confidence interval: 77.9-94.0%) and 97.2% (95% confidence interval: 89.4-99.3%) in the 360 and 480 mg groups, respectively. The median percent change in serum prostate-specific antigen level from baseline to Day 364 was -95.05% and -96.43% in the 360 and 480 mg groups, respectively; the proportion of patients with prostate-specific antigen failure was 2.7% and 1.3%. The most frequent adverse event was injection site reaction; however, this did not cause any patient to discontinue treatment. CONCLUSIONS: The 3-month dosing regimen of degarelix 360/480 mg was effective and well tolerated for treatment of Japanese prostate cancer patients. The 480 mg group showed a higher cumulative castration rate than the 360 mg group; thus, 480 mg was considered to be the optimal clinical dosage for future Phase III trials.

Efficacy and safety of sequential use of everolimus in Japanese patients with advanced renal cell carcinoma after failure of first-line treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitor: a multicenter phase II clinical trial.

OBJECTIVE: Many studies have shown the efficacy of everolimus after pretreatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors. We investigated the efficacy and safety of everolimus as a second-line treatment after the failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy in Japanese patients with advanced renal cell carcinoma. METHODS: This was an open-label, multicenter, phase II trial conducted in Japan through the central registration system. A total of 57  patients were enrolled. Patients were administered 10 mg of everolimus q.d. orally. The primary efficacy endpoint was progression-free survival achieved by administration of everolimus. RESULTS: The median progression-free survival of patients administered everolimus was 5.03 months (95% confidence interval: 3.70-6.20). The median overall survival was not reached. The objective response rate was 9.4% (95% confidence interval: 3.1-20.7). The progression-free survival in the group of <100% relative dose intensity was 6.70 months (95% confidence interval: 4.13-11.60), and that in the group of 100% relative dose intensity was 3.77 months (hazard ratio: 2.79, 95% confidence interval: 2.77-5.63). The commonly observed adverse events and laboratory abnormalities were stomatitis (49.1%), hypertriglyceridemia (26.4%), interstitial lung disease (26.4%), anemia (22.6%) and hypercholesterolemia (22.6%). CONCLUSION: The median progression-free survival was almost similar to that recorded in the RECORD-1 study, whereas prolongation of overall survival was observed in the present study compared with the RECORD-1 study. The treatment outcomes of first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy and second-line everolimus treatment in Japanese patients were successfully established in the present study.