Tags

chemotherapy

  • [(18)F]Fluorodeoxyglucose-positron emission tomography/computed tomography response evaluation can predict histological response at surgery after induction chemotherapy for oligometastatic bladder cancer.

    Patients with limited metastatic and locally advanced bladder cancer have a poor prognosis, and no definite treatment recommendations exist. However, long-term survival is possible for selected patients if surgery is combined with multiple courses of chemotherapy (i.

    Published June 7, 2017
  • [Local treatment of penile cancer].

    In recent decades, the local treatment of penile cancer has focused primary on the removal of the primary tumor. Due to the significant psycho-oncological effects of treating the primary tumor, the guidelines on penile cancer now contain a clear recommendation for preserving the target organ and prior to each surgical procedure histological examination should be performed to confirm the penile cancer.

    Published April 17, 2018
  • [Management of neuroendocrine prostate carcinoma: Literature review].

    Neuroendocrine prostate carcinoma is a rare entity causing both diagnostic and therapeutic issues. There are basically four histological forms (adenocarcinoma with neuroendocrine differentiation, carcinoid tumors, small cell neuroendocrine carcinomas, large cell neuroendocrine carcinomas), which can be pure or mixed associated with prostatic carcinoma.

    Published June 28, 2016
  • [Metastatic prostate cancer : Update: position paper for the use of chemotherapy].

    Taxen-based chemotherapy has been established as an effective treatment option in castration-resistant metastatic prostate cancer (mCRPC). Randomized phase III studies, however, have shown that even in the hormone-naïve metastatic state, the early use of chemotherapy in addition to the classical androgen deprivation therapy (ADT) approach leads to a significant increase in median overall survival.

    Published July 18, 2017
  • [Postchemotherapy residual tumour resection in complex metastatic sites of advanced testicular germ cell tumours].

    INTRODUCTION - Postchemotherapy residual tumour resection (PC-RTR) is an integral part of the multimodal therapy for advanced testicular germ cell tumours. Depending on the extent and localisation of the residual mass, PC-RTR may necessitate a multidisciplinary procedure (which should be planned preoperatively), to resolve even complex situations in an oncologically sound manner, with lower treatment-related morbidity The aim of article is to report on the interdisciplinary management of complex residual masses.

    Published February 3, 2016
  • [ypT0N0 after neoadjuvant chemotherapy and cystectomy for muscle-invasive bladder cancer: Incidence and prognosis. A review from the Bladder group of the French Committee of Oncology].

    Neoadjuvant chemotherapy (NAC) is recommended for localized muscle-invasive bladder cancer when patients are fit for cisplatin-based chemotherapy. A pathological complete response can be observed, corresponding to ypT0N0 stage on the radical cystectomy specimen.

    Published September 18, 2018
  • A care bundle to improve perioperative mitomycin use in non-muscle-invasive bladder cancer.

    Intravesical chemotherapy administered within 24 h of the first resection of non-muscle-invasive bladder cancer (NMIBC) reduces recurrence rates and prolongs recurrence-free intervals. However, there is considerable variation in the use of intravesical chemotherapy amongst urologists.

    Published April 10, 2018
  • A comparison of the CARG tool, the VES-13, and oncologist judgment in predicting grade 3+ toxicities in men undergoing chemotherapy for metastatic prostate cancer.

    Since the benefits of chemotherapy in treating older men with metastatic castration-resistant prostate cancer (mCRPC) are modest, validated tools that predict the risk of treatment toxicity may aid clinical decision-making.

    Published October 27, 2016
  • A Phase II Study of Weekly Docetaxel as Second-Line Chemotherapy in Patients With Metastatic Urothelial Carcinoma.

    Docetaxel is commonly used for second-line therapy for metastatic urothelial carcinoma (UC). However, myelosuppression is a substantial concern when the traditional 3-week docetaxel cycle is used. The present multicenter phase II study evaluated the efficacy and safety of weekly docetaxel as second-line chemotherapy for metastatic UC.

    Published October 22, 2015
  • A prospective multicenter study of intermittent chemotherapy with docetaxel and prednisolone for castration-resistant prostate cancer.

    The optimal schedule of docetaxel chemotherapy for castration-resistant prostate cancer is unknown, although continuous administration is accepted as the standard. We conducted a Phase II trial to evaluate the outcome of intermittent docetaxel and prednisolone therapy in castration-resistant prostate cancer.

    Published March 15, 2016
  • A questionnaire survey on attitude toward sperm cryopreservation among hematologists in Japan.

    Advances in multimodal treatment have led to dramatic improvement in cancer treatment outcomes. It is now necessary to consider cancer patients' holistic quality of life. Fertility preservation is the top concern for cancer survivors of reproductive age.

    Published November 25, 2016
  • Abiraterone acetate in metastatic castration-resistant prostate cancer - the unanticipated real-world clinical experience.

    BACKGROUND - There is much interest in confirming whether the efficacy of abiraterone acetate (AA) demonstrated within the trial setting is reproducible in routine clinical practice. We report the clinical outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with AA in real-life clinical practice.

    Published March 31, 2016
  • Activity of cabazitaxel in patients with metastatic castration-resistant prostate cancer after treatment with single or dual regimens of novel androgen receptor-targeting agents.

    The purpose of this study was to evaluate the efficacy of cabazitaxel for patients with metastatic castration-resistant prostate cancer (mCRPC) after sequential therapy with docetaxel (DTX) and single or dual regimens of novel androgen receptor-axis-targeted (ARAT) agents.

    Published August 24, 2017
  • Acute Aortic Dissection Following Treatment for Castration-Resistant 
Prostate Cancer.

    A 65-year-old man presents to the emergency department with increasing back pain. His history includes hypertension, peripheral neuropathy, duodenal ulcer, superior mesenteric vein thrombus, stage IIB colon cancer treated with surgery and adjuvant chemotherapy, renal cell carcinoma treated with surgery, and prostate cancer treated with surgery and radiation.

    Published July 1, 2016
  • Addition of Docetaxel to Androgen Deprivation Therapy for Patients with Hormone-sensitive Metastatic Prostate Cancer: A Systematic Review and Meta-analysis.

    Several randomized clinical trials (RCTs) have recently tested the early addition of docetaxel to androgen deprivation therapy (ADT) in hormone-sensitive metastatic prostate cancer (PCa).

    To perform a systematic review and meta-analysis of RCTs evaluating the combination of docetaxel and ADT in hormone-sensitive metastatic PCa.

    Published October 13, 2015
  • Addressing taxane resistance in metastatic castration-resistant prostate cancer: a focus on chaperone proteins.

    Despite the significant survival benefit of taxane therapy in metastatic castration-resistant prostate cancer (mCRPC), all patients inevitably develop treatment resistance. An understanding of resistance mechanisms has led to new therapies for prostate cancer (cabazitaxel, abiraterone and enzalutamide), all of which have improved survival following first-line docetaxel.

    Published October 14, 2016
  • Addressing the expected survival benefit for clinical trial design in metastatic castration-resistant prostate cancer: Sensitivity analysis of randomized trials.

    We performed a sensitivity analysis, cumulating all randomized clinical trials (RCTs) in which patients with metastatic castration-resistant prostate cancer (mCRPC) received systemic therapy, to evaluate if the comparison of RCTs may drive to biased survival estimations.

    Published December 9, 2015
  • Adjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and network meta-analysis of randomized clinical trials.

    Although adjuvant chemotherapy (ACH) is widely used in clinical practice for the management of muscle-invasive bladder cancer (MIBC), a consensus has yet to be established on which ACH regimen is the most effective for improving postoperative survival.

    Published November 13, 2017
  • Aetiology, clinical presentation and treatment of testicular cancer.

    Testicular cancer is a highly treatable and curable malignancy. It typically affects men aged 15-35 years and is the most common malignancy in this age group. Nurses have an important role in assisting patients to cope with the diagnosis and understand the treatment options.

    Published March 20, 2018
  • Androgen deprivation therapy as backbone therapy in the management of prostate cancer.

    Androgen deprivation therapy (ADT) is well established as a backbone therapy for metastatic prostate cancer (mPCa), and both European and American guidelines emphasize the importance of maintaining ADT after progression to metastatic castration-resistant prostate cancer (CRPC).

    Published December 16, 2016
  • Androgen-deprivation therapy plus chemotherapy in metastatic hormone-sensitive prostate cancer. A systematic review and meta-analysis of randomized clinical trials.

    OBJECTIVE - To assess the efficacy and toxicity of androgen-deprivation therapy (ADT) plus chemotherapy in patients with hormone-sensitive metastatic prostate cancer.

    METHODS - Randomized clinical trials were identified after systematic searching of databases and conference proceedings.

    Published April 11, 2016
  • Annular rectal constriction caused by infiltrating bladder cancer: A case report.

    A 69-year-old man was referred to our hospital with chief complaints of urinary incontinence, pollakiuria, thin stools and edema of the left lower extremity. Computed tomography and magnetic resonance imaging revealed bilateral hydronephrosis, thickening of the rectal and posterolateral bladder walls, and enlargement of the left obturator lymph nodes, suggesting metastasis.

    Published January 24, 2017
  • Anticancer Activity and Tolerance of Treatments Received Beyond Progression in Men Treated Upfront with Androgen Deprivation Therapy With or Without Docetaxel for Metastatic Castration-naïve Prostate Cancer in the GETUG-AFU 15 Phase 3 Trial.

    Androgen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE.

    Published November 2, 2017
  • Antitumour activity of platinum compounds in advanced prostate cancer - a systematic literature review.

    BACKGROUND - For men with advanced castration-resistant prostate cancer (CRPC), several treatment options are available, including androgen receptor (AR) pathway inhibitors (abiraterone acetate, enzalutamide), taxanes (docetaxel, cabazitaxel) and a radionuclide (radium-223).

    Published April 11, 2016
  • Application of Mixture Design Response Surface Methodology for Combination Chemotherapy in PC-3 Human Prostate Cancer Cells.

    Combining chemotherapeutics to treat malignant tumors has been shown to be effective in preventing drug resistance, tumor recurrence, and reducing tumor size. We modeled combination drug therapy in PC-3 human prostate cancer cells using mixture design response surface methodology (MDRSM), a statistical technique designed to optimize compositions to achieve the most desirable result.

    Published June 15, 2018
  • Approved checkpoint inhibitors in bladder cancer: which drug should be used when?

    The treatment of advanced metastatic urothelial carcinoma has recently evolved with the approval of five checkpoint inhibitors. In the second-line setting, in patients who have progressed on cisplatin-based chemotherapy, pembrolizumab, atezolizumab, durvalumab, nivolumab and avelumab are United States Food and Drug Administration (FDA) approved.

    Published August 13, 2018
  • Assessment of quality of life in advanced, metastatic prostate cancer: an overview of randomized phase III trials.

    The chief therapeutic goal in metastatic prostate cancer is prolongation of survival with good quality of life . Quality of life (health-related) is often used as an endpoint parameter in phase III trials in metastatic prostate cancer, but the value of using HRQOL in this context has not been assessed to date.

    Published October 18, 2016
  • Association of Interleukin-6 and Other Cytokines with Self-Reported Pain in Prostate Cancer Patients Receiving Chemotherapy.

    Pain is a common and dose-limiting side effect of many potentially curative cancer chemotherapeutic agents. This chemotherapy-induced pain (CIP) affects the quality of life of cancer patients and survivors and hampers the optimal clinical management of chemotherapy in cancer patients.

    Published October 19, 2017
  • Baseline Glomerular Filtration Rate and Cisplatin- Induced Renal Toxicity in Urothelial Cancer Patients.

    Cisplatin eligibility for clinical trials has been defined as glomerular filtration rate (GFR) ≥ 60 mL/min due to the risk of nephrotoxicity in patients with renal impairment. For urothelial cancer, substitution of carboplatin instead of cisplatin compromises outcomes.

    Published October 3, 2017
  • Beyond first-line systemic treatment for metastatic urothelial carcinoma of the bladder.

    Metastatic urothelial carcinoma of the bladder is a rarely curable disease. Patients receive systemic therapy with limited response rates and survival benefits. The rescue regimens of these patients who have failed first-line treatment had remained problematic until the recent advances.

    Published September 14, 2018
  • Beyond the Abstract - A comparison of the outcomes of neoadjuvant and adjuvant chemotherapy for clinical T2-T4aN0-N2M0 bladder cancer, by Matthew Wosnitzer, MD and James M. McKiernan, MD

    BERKELEY, CA (UroToday.com) - Although neoadjuvant and adjuvant platinum-based systemic chemotherapy have been studied individually for locally advanced bladder cancer, these two modalities have not been compared comprehensively.

    Published October 31, 2011
  • Beyond the Abstract - Current chemotherapeutic strategies against bladder cancer , by Yozo Mitsui, MD., Et Al.

    BERKELEY, CA (UroToday.com) - Urothelial cancer is a chemotherapy-sensitive malignancy, with the regimen of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) until recently considered to be the first choice for chemotherapy, however its adverse effects and poor long-term outcome results remain challenging problems. In addition, effective treatment for the cases showing resistance to M-VAC or recurrent cases after first-line chemotherapy has not to been established.

    Published November 17, 2011
  • Beyond the Abstract - In vitro and in vivo responses of advanced prostate tumors to PSMA ADC, an auristatin-conjugated antibody to prostate-specific membrane antigen, by William Olson, PhD and Warren Heston, PhD

    BERKELEY, CA (UroToday.com) - Despite the recent introduction of new treatment options for advanced prostate cancer, metastatic disease remains incurable and claims the lives of more than 200,000 men annually worldwide.(1)

    Published November 11, 2011
  • Beyond the Abstract - Successful treatment of postchemotherapy azoospermia with microsurgical testicular sperm extraction: The Weill Cornell experience, by Peter N. Schlegel, MD

    BERKELEY, CA (UroToday.com) - In the past, men who were azoospermic after chemotherapy were routinely considered sterile, and fertility options included only donor sperm (substitutive therapy).

    Published October 12, 2011
  • Biomarker in Cisplatin-Based Chemotherapy for Urinary Bladder Cancer.

    The treatment of metastasized bladder cancer has been evolving during recent years. Cisplatin based chemotherapy combinations are still gold standard in the treatment of advanced and metastasized bladder cancer.

    Published November 20, 2015
  • Bladder Urothelial Carcinoma with Peritoneal Involvement: Benefit of Continuous Maintenance Chemotherapy.

    We investigated bladder urothelial carcinoma with peritoneal involvement.

    Inclusion criteria were: pathology-confirmed urothelial carcinoma; peritoneal spread identified on computed tomographic (CT) scans performed initially or after either cystectomy or concomitant chemoradiotherapy (CCRT), and absence of visceral metastases; and chemotherapy administered after peritoneal spread was diagnosed.

    Published November 1, 2017
  • Building the Case for Adjuvant Chemotherapy after Radical Cystectomy.

    The main objective of the article published by Galsky et al. was to explore the impact of adjuvant chemotherapy on overall survival (OS) in patients with muscle invasive bladder cancer after radical cystectomy.

    Published April 15, 2016
  • Burden of Metastatic Castrate Naive Prostate Cancer Patients, to Identify Men More Likely to Benefit from Early Docetaxel: Further Analyses of CHAARTED and GETUG-AFU15 Studies.

    Docetaxel (D) at the time of starting androgen deprivation therapy (ADT) for metastatic castrate naive prostate cancer shows a clear survival benefit for patients with high-volume (HV) disease. It is unclear whether patients with low-volume (LV) disease benefit from early D.

    Published February 27, 2018
  • Cabazitaxel regimens inhibit the growth of prostate cancer cells and enhances the anti-tumor properties of PEDF with various efficacy and toxicity.

    Taxanes chemotherapies represent the major therapeutic alternative for symptomatic mCRPC. While docetaxel is the most commonly prescribed Taxane for mCRPC; cabazitaxel has been approved for patients unresponsive to docetaxel.

    Published May 16, 2018
  • Can urologists introduce the concept of "oligometastasis" for metastatic bladder cancer after total cystectomy?

    We investigated whether the concept of oligometastasis may be introduced to the clinical management of metastatic bladder cancer patients. Our study population comprised 128 patients diagnosed with metastatic bladder cancer after total cystectomy at our 6 institutions between 2004 and 2014.

    Published February 2, 2018
  • Cancer therapeutics-related cardiac dysfunction in a patient treated with abiraterone for castration-resistant prostate cancer.

    Abiraterone is an agent effective for castration-resistant prostate cancer, but there have been no reports of cardiotoxic effects inducing cardiomyopathy, to our knowledge. We present a case of an 86-year-old man with castration-resistant prostate cancer treated with abiraterone.

    Published September 12, 2018
  • CARG tool’s ability to predict older prostate cancer patients’ risk of toxicity: Beyond the Abstract

    Prostate cancer is one of the leading causes of cancer death in American men and mostly affects men above age 65. [1]  The American Cancer Society predicts 161,360 new cases of prostate cancer and 26,730 deaths from prostate cancer in the United States in the year 2017. [1]  Although fewer than 10% of people are diagnosed with de novo metastatic disease, many men with early stage prostate cancer will eventually develop metastatic disease. The initial treatment of metastatic disease is androgen deprivation therapy, but this is only effective for a few years, after which the disease continues to progress.  At this point it is referred to as metastatic castrate resistant prostate cancer (mCRPC).  About 10-20% of people are diagnosed with mCRPC within 5 years of a diagnosis of prostate cancer, but more than 50% of patients with mCRPC die within 3 years. [2]  mCRPC is currently defined as the progression of the prostate cancer despite castrate levels of testosterone (usually defined as <1.7nmol/L). [2]  Progression to mCRPC is typically associated with worsening symptoms, declining quality of life and worsening pain.  However, mCRPC may be helped by other forms of hormone therapy such as the androgen receptor axis-targeted (ARAT) agents Abiraterone and Enzalutamide because it is not completely hormone-refractory. [3]  Patients who become resistant to ARAT therapy usually are considered for chemotherapy. [4]  In 2004, docetaxel became the standard of care for mCRPC. Later, cabazitaxel was also found to be beneficial in patients with mCRPC that progressed after receiving docetaxel therapy. [2]

    Chemotherapy

    Chemotherapy remains the treatment of choice in symptomatic mCRPC, but survival benefits after undergoing chemotherapy are modest (on the order of a few months).  In comparison to mitoxantrone (the prior standard chemotherapy agent), docetaxel was associated with better pain control, quality of life and more frequent PSA responses. [5]  However, chemotherapy can also be associated with significant toxicity, with 18-44% rates of grade 3 or higher toxicity.  National Cancer Institute Common Terminology Criteria for Adverse Events defines grade 3 as severe, grade 4 as life-threatening or disability and grade 5 as death. [6]  Common toxicities from chemotherapy include neutropenia, generalized weakness, bone pain, fatigue, peripheral edema and mucositis.  The most common grade 3 to 5 toxicities with docetaxel are: neutropenia, leucopenia, anemia, fatigue, infection and dehydration. [5]

    Currently, there is a need to find tools that can help identify men who may be more or less likely to experience serious toxicity from chemotherapy because it could help during treatment decision-making. Predicting toxicities would help doctors determine the side effects and toxicities that specific patients might develop before prescribing the treatment.  This way, it would make it easier for them to determine which treatment method would work, at which dose and method of delivery.  Making a more informed decision can be important in this setting because of the increased risk of death or functional decline.  It is especially helpful to be able to predict these toxicities in older adults because the risk of toxicity increases with age.  In practice, chemotherapy is less likely to be given to older adults due to the concerns about their ability to tolerate it. [6]  Many older adults tend to place an increasing value on avoiding treatments that adversely affect their quality of life or functional independence. [7]  Since older adults have a higher risk of toxicity and place an increasing importance on quality of life, oncologists may find it harder to suggest the best treatment option.  Hence, it would be useful to be able to predict toxicities from chemotherapy.  This advancement in toxicity prediction would also help select up-front treatment modifications such as dose reduction or the addition of colony-stimulating factors to reduce toxicity.

    Tools such as the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 5-point scale are currently used to determine risk by assessing a patient’s level of function and capability to perform self-care.  Although this tool is a prognostic factor for survival and may help select which patients should not get chemotherapy, it is a poor predictor of toxicity risk because it is subjective, being subject to bias and high interobserver variability. [8]  Oncologist judgement in stratifying patients into those at lower or higher risk of toxicity may be better, but it has rarely been formally compared against measures such as the ECOG PS.  Finally, the agreement between currently used tools such as PS and clinical judgement by oncologists is still quite low. [9]

    Our study sought to identify tools that could help inform treatment decision-making by improving the ability to predict a patient’s risk of chemotherapy toxicity.  Distinguishing men at lower and higher risk of severe toxicity in men with mCRPC would help make better treatment decisions and allow a more informed decision about the risks and benefits of chemotherapy.  In patients with very high risks of toxicity that may counterbalance any perceived benefits, there are four main options besides conventional dose chemotherapy: (a) reduced-dose chemotherapy; (b) use of colony-stimulating factors to reduce neutropenia and related complications; (c) alternative, gentler agents or clinical trials of novel therapies; (d) best supportive care.  While our study did not focus on which treatment might be best, we sought to validate the Vulnerable Elders Survey-13 (VES-13) and Cancer and Aging Research Group (CARG) tool in mCRPC with the goal of helping a clinician’s judgment. 

    VES-13

    The VES-13 is a brief (3-4 minutes), self-report tool that measures vulnerability.  The initial purpose of developing this tool was to better screen older persons at risk of health deterioration. [10]  In the original study, vulnerable older people were defined as persons age 65 and older who were at increased risk of functional decline or death over 2 years. [10]  The instrumental activities of daily living (IADLs) and activities of daily living (ADLs) that the VES-13 focuses on include shopping, performing light housework, managing finances, preparing meals, using the telephone, bathing, dressing, transferring, toileting, walking across the room, and eating. [10]   However, its ability to predict grade 3-5 chemotherapy toxicity has yet to be studied. 

    CARG 

    The CARG tool uses a combination of 11 parameters, including age, tumor and treatment characteristics, laboratory data, and specific geriatric assessment parameters to help predict grade 3-5 chemotherapy toxicity in older patients with cancer.  It categorizes people into low, intermediate and high risk of severe chemotherapy toxicity, in our case grade 3+ chemotherapy toxicity.  It does include a geriatric assessment questionnaire with 6 domains: functional status, co-morbidity, psychological state, social activity, social support, and nutrition.  The purpose of developing the CARG tool was to identify risk factors for chemotherapy toxicity in older adults undergoing various chemotherapy regimens and create a user-friendly risk stratification schema for chemotherapy toxicity. [6]  The CARG tool was derived from a study of 500 patients undergoing a variety of chemotherapy regimens for various solid tumors. The CARG tool was recently validated externally [11] and helps to identify patients at greatest risk of chemotherapy toxicity.  Although the CARG tool has been proven in a mixed cohort of patients with various cancers, there are no validation data for patients with mCRPC, and only 10% of the patients in the original study had genitourinary cancers. [6]  Since different chemotherapy regimens have different toxicity risks, it is important to validate such tools in a more homogeneous cohort to ensure findings are similar to mixed cohorts. 

    Oncologist Judgment

    For our study, we had each patient’s medical oncologist rate the patient’s risk of chemotherapy toxicity on a 10-point scale.  “Oncologists are left with little guidance when it comes to identifying risk factors other than chronologic age or performance status, neither of which has been shown to predict well in heterogeneous older adult populations.” [6] 

    Methods

    We recruited men aged 65 or older with mCRPC who were starting either first-line chemotherapy (receiving chemotherapy for the first time) or second-line chemotherapy (stopped first-line chemotherapy because of disease progression, toxicity, or other reasons).  All but two (4%) participants received docetaxel-based chemotherapy, and the majority (n=29, 63%) received the standard dose of 75 mg/m2 every 3 weeks.  Ten (22%) received a dose of 60 mg/m2, whereas 5 (11%) received a lower dose than this.  Subjects were recruited either prior to starting chemotherapy or within the first two cycles as long as there was no dose reduction.  Men unable to come for study visits or with a life expectancy of less than 3 months, a major neuropsychiatric abnormality, or limited English were excluded from the study.

    We collected socio-demographic and medical information on all subjects at baseline, as well as physical performance measures (grip strength, timed up and go, and timed chair stands).  The CARG and VES-13 tools were administered as well.  The CARG toxicity prediction model was used to stratify patients into three groups (low, intermediate, and high risk) based on risk for grade 3+ chemotherapy toxicity.  The VES-13 was used to measure vulnerability, which was defined by a score of 3 or greater.  This cut-off point follows the conventional scoring system, but we also examined cut-offs of 2 or greater and 4 or greater.  We also asked each subject’s treating physician to provide an estimate of the risk of chemotherapy toxicity on a scale from 1 (lowest risk) to 10 (highest risk).  Oncologists were not told the results of the other assessment tools used in the study. 

    Following the baseline visit, follow-up assessments were performed after each cycle of chemotherapy (every 3 weeks) and after the final cycle.  At each visit, a trained research coordinator recorded chemotherapy-related toxicities using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4).  Laboratory-based toxicities such as neutropenia were based on blood tests performed every three weeks.  These same procedures were followed to record toxicity for men who were recruited after already having started chemotherapy, including for cycles administered before being enrolled on the study.

    Sample sizes were based on the assumption that we would see the same rate of toxicity as in the original CARG study (i.e. 30% risk of grade 3+ toxicity for the low risk group, 52% for intermediate, and 83% for high) [6] and that equal proportions of patients would be enrolled in each risk group (i.e. one-third for each).  Based on these assumptions, we calculated that we would require 45 patients. 

    Results

    46 men were recruited for the study with a mean age of 75.  These participants had a median PSA level at baseline of 243.7 ng/mL and had relatively few other major medical problems (median Charlson Comorbidity Index score of 0).  Although participants had a fairly high performance status (mean Karnofsky score of 77%), 50% were considered vulnerable based on the VES-13.  Based on the CARG tool, only 2 (4%) patients were considered low risk, 29 (63%) were intermediate, and 15 (33%) were high risk of severe chemotherapy toxicity. 

    Grade 3+ and grade 2 chemotherapy toxicity were experienced by 20% and 67% of patients, respectively.  The most common grade 3-5 toxicities were neutropenia (30%), generalized weakness (23%), and bone pain (15%), and the most common grade 2 toxicities were fatigue (35%), peripheral edema (7%), and mucositis (7%).

    Grade 3+ toxicity was observed in 0 (0%), 5 (17%) and 4 (27%) patients in low, intermediate, and high CARG risk groups respectively, suggesting an incremental pattern across risk groups.  However, this pattern was not statistically significant (p = 0.65).  22% of patients considered vulnerable by the VES-13 experienced grade 3+ toxicity, compared to 17% of patients considered non-vulnerable (p = 0.71).  Age, comorbidity, Karnofsky performance score, and baseline physical performance measures did not seem to be predictors of grade 3+ toxicity.  In addition, oncologist judgment of toxicity risk was a relatively poor predictor of actual toxicity.

    The ability of the CARG tool to predict grade 2 toxicity appeared to be higher than the ability of the VES-13 to predict these toxicities, but this was not statistically significant, likely due to our small sample size (p = 0.072 for CARG, 0.75 for VES-13).  Limiting the analyses to only those participants who were recruited prior to starting chemotherapy did not alter the findings.

    The rates of grade 3+ toxicity found in our cohort were relatively low overall: only 20% compared to the 53% observed in the original CARG study.  The same pattern was found in the three individual risk groups, with lower rates of toxicities observed in each compared to the original CARG study.  However, the rate of toxicity in our cohort was similar to rates reported in other studies of older men with mCRPC.  For example, the TAX327 trial by Tannock et al. reported severe adverse events in 26% of subjects, and grade 3+ neutropenia in 32%. [5]

    Although we did not find statistically significant results for either of the tools tested, we did observe three key findings in our study.  First, the risk of grade 3+ toxicity with docetaxel-based chemotherapy in the mCRPC population is lower overall and across CARG risk groups compared to the rates observed in the original study, which used data from patients with a variety of cancers.  However, we still found that there was a gradient of toxicity risk across the different CARG risk groups (i.e. 0% in low, 17% in moderate, and 27% in the high risk group).  Therefore, there is a need for further validation studies conducted with older men with mCRPC.

    Second, our data on the performance of the VES-13 are the first in this population.  Even though our findings were negative, we believe they warrant further investigation because of the ease of use and emerging value of the VES-13 in other geriatric oncology settings (e.g. 12).  Third, we also provided the first data looking at oncologist judgment of toxicity risk, and compared that to the CARG and VES-13 tools.  For tools to be useful in a busy clinical setting, they must provide better predictive ability than the usual clinical care.  Therefore, further investigation in this area is important.

    Some other limitations include the fact that we conducted our study at a single academic cancer center, limiting generalizability, and did not use the CRASH tool, another popular tool for predicting toxicities. [13]  Future studies should directly compare the CRASH and CARG tools in the mCRPC setting.  Lastly, the 10-point rating scale we used for oncologist predictions has not been validated in this context, and we did not provide any numerical anchors.  Therefore, the different ratings may have meant different things to different oncologists.  Further investigation is warranted in these areas.

    Conclusion

    In summary, toxicity with docetaxel in a cohort of older men in usual clinical practice was lower than predicted by the CARG tool.  Although the CARG tool appeared to differentiate those at lower versus higher risk of chemotherapy toxicity and was better than clinician judgement or ECOG PS, a larger validation study is needed.

    Written By: Thavalis Ja, Rathore Ma, Breunis Ha, Alibhai SMHa,b,c
    a. Department of Medicine, University Health Network 

    b. Department of Medicine, University of Toronto 
    c. Institute of Health Policy, Management and Evaluation, University of Toronto 

    References 

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    7. Rose JH, O'Toole EE, Dawson NV, Lawrence R, Gurley D, Thomas C, Hamel MB, Cohen HJ. Perspectives, preferences, care practices, and outcomes among older and middle-aged patients with late-stage cancer. Journal of Clinical Oncology. 2004 Dec 15; 22(24):4907-17. 
    8. Kelly CM, Shahrokni A. Moving beyond Karnofsky and ECOG performance status assessments with new technologies. Journal of Oncology. 2016 Mar 15; 6186543.
    9. Sørensen JB, Klee M, Palshof T, Hansen HH. Performance status assessment in cancer patients. An inter-observer variability study. British Journal of Cancer. 1993 Apr; 67(4):773-5.
    10. Saliba D, Elliott M, Rubenstein LZ, Solomon DH, Young RT, Kamberg CJ, Roth C, MacLean CH, Shekelle PG, Sloss EM, Wenger NS. The Vulnerable Elders Survey: a tool for identifying vulnerable older people in the community. Journal of the American Geriatrics Society. 2001 Dec 1; 49(12):1691-9.
    11. Hurria A, Mohile S, Gajra A, Klepin H, Muss H, Chapman A, et al.  Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer.  Journal of Clinical Oncology. 2016 Jul 10; 34(20:2366-71.
    12. Luciani A, Ascione G, Bertuzzi C, Marussi D, Codeca C, Di Maria G, et al.  Detecting disabilities in older patients with cancer: comparison between comprehensive geriatric assessment and vulnerable elders survey-13.  Journal of Clinical Oncology. 2010 Apr 20; 28(12):2046-50.
    13. Extermann M, Boler I, Reich RR, Lyman GH, Brown RH, DeFelice J, et al. Predicting the risk of chemotherapy toxicity in older patients: The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer. 2011 Nov 9; 118(13):3377-86.
    Read the Abstract
    Published June 1, 2017
  • Case report of a primary prostatic urothelial carcinoma patient with sustained fever.

    A 77-year-old-male patient presented with recurrent gross hematuria for 3 months with a fever for 1 month, and so was admitted to The First Hospital of Tsinghua University. The medical history revealed the patient exhibited no symptoms of night sweat, dysuria, or abdominal pain.

    Published August 28, 2018
  • Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2015.

    The purpose of this amendment is to incorporate relevant newly-published literature to better provide a rational basis for the management of patients with castration-resistant prostate cancer (CRPC).

    Published November 6, 2015
  • Chemoradiation for organ preservation in the treatment of muscle-invasive bladder cancer.

    Standard therapy for muscle invasive bladder cancer includes neoadjuvant chemotherapy followed by radical cystectomy with urinary diversion. Three decades of interest in primary radiation and chemotherapy for bladder preservation have yielded mature that deserve closer examination.

    Published May 6, 2016
  • Chemotherapy at First Diagnosis of Advanced Prostate Cancer - Revolution or Evolution? Findings from a British Uro-oncology Group UK Survey to Evaluate Oncologists' Views on First-line Docetaxel in Combination with Androgen Deprivation Therapy in Castrate

    AIMS - There have been three randomised trials investigating docetaxel in combination with androgen deprivation therapy as first-line therapy for hormone-sensitive metastatic and locally advanced/high-risk prostate cancer.

    Published February 19, 2016
  • Chemotherapy following radium-223 dichloride treatment in ALSYMPCA.

    BACKGROUND - Radium-223 prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases, regardless of prior docetaxel. Whether or not chemotherapy can be safely administered following radium-223 treatment is of clinical importance.

    Published March 29, 2016
  • Chemotherapy for metastatic testicular cancer: The first nationwide multi-institutional study by the Cancer Registration Committee of the Japanese Urological Association.

    To assess clinicopathological data and oncological outcomes focused on metastatic testicular cancer patients, who received chemotherapy as the initial treatment, in the nationwide multi-institutional study by the Cancer Registration Committee of the Japanese Urological Association.

    Published August 18, 2018
  • Chemotherapy for Muscle-Invasive Bladder Cancer.

    In the last 25 years, there has been an improved understanding of the pathogenesis of muscle-invasive bladder cancer (BC). Development of new treatment strategies has followed. We have progressed from the awareness of the efficacy of platinum compounds, especially cisplatin, as single agents to the development of effective drug combinations with greater attention in improving safety profiles while impacting on survival.

    Published January 29, 2016
  • Chemotherapy in frail elderly patients with hormone-refractory prostate cancer: A "real world" experience.

    BACKGROUND - In elderly patients affected by metastatic castration-resistant prostate cancer (mCRPC) chemotherapic treatment may be the choice if one considers not only the chronological age, but also the clinical status, the functional reserve, and the vulnerability of patients.

    Published March 30, 2016

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