Evaluation and management of hypersensitivity reactions to chemotherapy agents.

Hypersensitivity reactions to chemotherapy drugs pose significant difficulties in management, especially when no suitable alternative is available or acceptable and delay in continuation of treatment may be life-threatening. Such reactions may be IgE- or non-IgE-mediated and have varied manifestations. Timely recognition and treatment of life-threatening hypersensitivity reactions are essential. Identification of patients at high risk of developing hypersensitivity reactions allows risk stratification to guide clinical decision-making. Skin testing for carboplatin hypersensitivity has good predictive value but is not yet established for oxaliplatin and taxane hypersensitivity. Rapid desensitisation may be considered if no suitable alternative drug is available. Available protocols have shown good safety and efficacy but must be performed in an appropriate setting with adequate monitoring. There are many avenues for research into the utility of skin testing for other chemotherapy agents as well as in vitro tests.

Management of kidney cancer in Asia: resource-stratified guidelines from the Asian Oncology Summit 2012.

Treatment of renal-cell carcinoma has progressed over the past decade, in terms of surgical and systemic therapy. Current treatment guidelines are based on clinical evidence, but do not take into account resource limitations among different countries. These limitations, which include financial and logistical challenges and lack of skilled health-care professionals, have the greatest effect in low-income countries. This consolidated statement gives treatment recommendations for renal-cell carcinoma that are based on clinical evidence and stratified according to extent of resource availability. The statement was formulated by a panel of urologists, medical oncologists, and clinical oncologists from Asian countries, at a consensus session on kidney cancer that was held as part of the 2012 Asian Oncology Summit in Singapore. Resource levels are defined according to a four-tier system (basic, limited, enhanced, and maximum), and treatment recommendations are specified based on availability of financial, skill, and logistical resources.

Nasal metastases from renal cell carcinoma are associated with Memorial Sloan-Kettering Cancer Center poor-prognosis classification.

Unusual sites of metastases are recognized in patients with renal cell carcinoma (RCC). However, the prognostic implications of these sites are not well understood. We used the Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification for metastatic RCC to evaluate 912 consecutive patients with RCC managed at the Singapore General Hospital between 1990 and 2009. Among these patients, 301 had metastases either at diagnosis or during the course of illness. Nasal metastases, all arising from clear cell RCC, were identified histologically in 4 patients (1.3% of those with metastasis). All 4 patients were classified as MSKCC poor prognosis by current risk criteria. Nasal metastases were significantly associated with lung and bone metastases. The frequency of nasal metastases in patients with metastatic RCC is about 1%, occurring predominantly in patients with clear cell RCC. Nasal metastases are associated with poor prognosis as estimated by the MSKCC risk classification, with attendant implications for selection of targeted therapy, and are usually associated with multi-organ dissemination, including concurrent lung and bone involvement.

Phase II trial of gemcitabine in combination with cisplatin in inoperable or advanced hepatocellular carcinoma.

INTRODUCTION: Advanced hepatocellular carcinoma (HCC) has a dismal prognosis and is notoriously chemo-resistant. We conducted a Phase II prospective study to evaluate the activity and tolerability of gemcitabine and cisplatin in chemo-naïve advanced hepatocellular carcinoma. The trial considered a "no further interest" response rate of 10% and a target response rate of 30%. Utilising a Simon's minimax two-stage design with a type I error of 0.05 and power of 80%, 25 subjects would be required. Fifteen patients would be needed in stage 1 and if fewer than 2 responses were observed, the trial would be stopped and lack of efficacy claimed. MATERIALS AND METHODS: Patients with advanced HCC, diagnosed based on histology or by World Health Organization (WHO) criteria, were administered gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on day 1 and day 8 of a 21-day schedule. Assessment of response based on computer tomography was performed after every 2 cycles of chemotherapy. RESULTS: The trial was stopped early due to a lack of efficacy. A total of 15 patients were accrued. Twelve patients were hepatitis B positive and the other 3 patients were negative for both hepatitis B and C. Only 1 patient had a history of prior heavy alcohol use. Two patients had Child C liver cirrhosis, 5 patients had Child B cirrhosis, and the remaining 8 patients had Child A cirrhosis. This regime was well tolerated and there was only 1 patient who experienced grade IV toxicities. Only 5 of 15 patients experienced grade III toxicities (nausea and emesis, 1 patient; anemia, 1 patient; thrombocytopenia, 1 patient; and neutropaenia, 2 patients). Only 1 patient experienced a partial response to the combination of gemcitabine and cisplatin. A further 3 patients experienced stable disease and 11 patients progressed on chemotherapy. The median time to progression was 6 weeks. The progression-free curve showed a sharp descent in the initial part of the study, suggesting that many patients had disease progression after enrollment. The median overall survival was 18 weeks. CONCLUSION: The progression-free survival and overall survival in our study were extremely short. Based on the results of our phase 2 study, we are unable to recommend further studies utilising gemcitabine and cisplatin combination in patients with advanced HCC.

Efficacy of low-dose ketoconazole in hormone refractory prostate cancer patients at the National Cancer Centre and The Cancer Institute, Singapore.

INTRODUCTION: The advent of prostate specific antigen (PSA) has resulted in an increased incidence of early detection of prostate cancer recurrence. Patients treated with androgen deprivation therapy (ADT) become hormone-resistant after 18 to 24 months. In patients with biochemical failure, where there is a rise in PSA but no objective evidence of metastases, or in whom there are small volume metastases but who are asymptomatic, there is no standard of care after ADT. Ketoconazole, an antimycotic which affects the synthesis of androgens and other steroids, has shown direct cytotoxic effects in prostate cancer cell lines in in-vitro studies. This study describes our experience with ketoconazole treatment for hormone refractory prostate cancer (HRPC). MATERIALS AND METHODS: A retrospective study of HRPC patients given ketoconazole at the National Cancer Centre and The Cancer Institute from 2004 to 2005 was performed. All eligible patients had histologically proven adenocarcinoma of the prostate and a rising PSA level despite ADT with orchidectomy or luteinising hormone-releasing hormone (LHRH) agonist therapy. All patients received 200 mg of ketoconazole thrice daily. Response was defined as a decline in PSA of at least 50% from the pre-treatment level and confirmed by a second PSA value 4 or more weeks later. The endpoints evaluated were the presence and duration of a response and the toxicity profile of the treatment. RESULTS: A total of 32 patients with HRPC were treated with ketoconazole. Twelve (38%) of the 32 patients had a greater than 50% decrease in their PSA values. The median duration of response was 6.75 months. The median time to reach PSA nadir was 3.5 months. Five patients continue to exhibit progression-free response at the time of writing. Ketoconazole was generally well tolerated. Eighteen (56%) patients recorded mild toxicities related to ketoconazole. There were no grade 3 or 4 toxicities. CONCLUSIONS: Low-dose ketoconazole bridges the gap in the continuum of treatment for patients who have failed ADT and in whom cytotoxic chemotherapy would have a significant impact on the quality of life. Its good toxicity profile, low cost and ease of administration makes it a viable option for this group of patients.

Outcomes of Dose-Attenuated Docetaxel in Asian Patients with Castrate-Resistant Prostate Cancer.

INTRODUCTION: High levels of toxicities have been observed when docetaxel is administered at the standard dose of 75 mg/m2 every 3 weeks (Q3W) in the real-world treatment of Asian patients with metastatic castrate-resistant prostate cancer (CRPC). This study aimed to evaluate the efficacy and tolerability of 2 attenuated regimens more widely used in an Asian setting to minimise toxicity - 60 mg/m2 Q3W and weekly docetaxel (20 mg/m2 to 35 mg/m2). MATERIALS AND METHODS: Medical records of 89 CRPC patients between December 2003 and April 2013 were reviewed. Pairwise statistical analysis was performed, comparing efficacy and safety outcomes of 75 mg/m2 Q3W and weekly docetaxel with 60 mg/m2 Q3W. Treatment endpoints used were prostate-specific antigen (PSA) response (decrease of ≥50% from baseline), pain improvement after cycle 2, overall survival, time to disease progression and radiological response. RESULTS: Patients who received docetaxel at 75 mg/m2 Q3W were younger than those who received 60 mg/m2 Q3W (62 years and 66 years, respectively; P = 0.0489). Both groups had similar response rates. Compared with patients on 60 mg/m2 Q3W, more patients on weekly regimens were symptomatic at baseline (63.2% and 87.5%, respectively; P = 0.0173). Longer overall survival was observed in the 60 mg/m2 Q3W arm than the weekly docetaxel arm (16.9 months and 10.6 months, respectively; P = 0.0131), though other measures of response did not differ significantly. CONCLUSION: Our data supports the use of 60 mg/m2 Q3W docetaxel which has similar efficacy and an acceptable toxicity profile compared to the standard 75 mg/m2 Q3W regimen. Weekly docetaxel has significant palliative benefits among symptomatic patients despite lower overall survival.

Metastatic malignant phaeochromocytoma: A rare entity that underlies a therapeutic quandary.

Phaeochromocytoma is a rare condition that provides a diagnostic challenge as a result of its variable presentation. Treatment of metastatic malignant phaeochromocytoma is also not well defined owing to its rarity. We present four such cases and a review of the literature. The database of the Singapore Cancer Registry was used to trace all cases of metastatic malignant phaeochromocytoma from 1984 to 2004, and the case records were then reviewed retrospectively. There were four patients with metastatic malignant phaeochromocytoma seen in Singapore in the last 20 years. Their variable clinical courses were reviewed and compared with current knowledge and overseas experience in the literature. We further discuss the difficulties in diagnosis, and the dilemma in appropriate management of such cases. Phaeochromocytoma remains a commonly missed diagnosis unless a high index of suspicion is maintained. Malignant phaeochromocytoma has a variable clinical course. There is a place for radical surgery if this can render the patient free of gross disease, or when it can achieve symptom control for palliation and improvement in quality of life. In the metastatic context, debulking surgery does not appear to be of curative benefit, although it may be undertaken for good palliation.

Response to docetaxel/carboplatin in patients with hormone-refractory prostate cancer not responding to taxane-based chemotherapy.

Few treatment options are available for patients with metastatic hormone-refractory prostate cancer (HRPC) that is not responsive to or continues to progress after taxane-based chemotherapy. Although single-agent carboplatin has modest activity in HRPC, carboplatin chemotherapy could induce a synergistic effect when combined with taxanes in patients with disease resistant to taxane-based chemotherapy. We report a case series of 4 consecutive patients treated with docetaxel (60-70 mg/m2) plus carboplatin (area under the curve of 4/5) following progression after taxane-based chemotherapy. Prostate-specific antigen levels decreased by > 50% in all 4 patients and were associated with improvement in symptoms in 3 of 4 patients. Treatment was well tolerated, with fatigue as the most common reported side effect. Patients received 4-11 cycles of treatment and, after initiation of docetaxel/carboplatin chemotherapy, survival ranged from 4.5 months to 12 months. In this small series, there is a suggestion of a greater than expected response with carboplatin and docetaxel for patients who exhibit disease progression despite taxane-based chemotherapy or do not respond to therapy. A clinical trial to evaluate this effect has been initiated.

Adrenal insufficiency in intestinal obstruction from carcinomatosis peritonei--a factor of potential importance in symptom palliation.

Corticosteroids are used in the management of intestinal obstruction (IO) in carcinomatosis peritonei. There is considerable overlap in the symptoms experienced in IO and functional adrenal insufficiency (AI). The success of symptom palliation in IO may be related to the presence of AI. The aim of this preliminary study was to evaluate the incidence of functional adrenal insufficiency in patients with IO and its relation to clinical outcome and symptom control. Twenty-nine consecutive patients with IO and carcinomatosis peritonei from gastrointestinal cancers admitted to our inpatient service between January and October 2002 were analyzed. They were screened for AI using the short corticotropin stimulation test. Thirteen patients (45%) had functional AI. Differences in characteristics of patients with normal adrenal function (Group 1) and adrenal insufficiency (Group 2) were not statistically significant. Time taken to control symptoms in Group 2 was longer. Mean duration of hospitalization per month of survival was two times longer in Group 2 relative to Group 1 (7.9 versus 4.0 days, P=0.011). Functional AI may be caused by cytokines produced in advanced cancer mediating direct adrenal suppression. Prompt corticosteroid therapy in the presence of AI may facilitate IO symptom palliation.

Efficacy and Safety of an Attenuated-Dose Sunitinib Regimen in Metastatic Renal Cell Carcinoma: Results From a Prospective Registry in Singapore.

BACKGROUND: The use of sunitinib at conventional doses (50 mg/d, 6-week cycles: 4 weeks of treatment, then 2 weeks of no treatment) in Asian patients with metastatic renal cell carcinoma (mRCC) is associated with high real-world toxicities. PATIENTS AND METHODS: Patients with mRCC treated with sunitinib between 2005 and 2012 at 4 centers representing a near-national cohort (n = 160) in Singapore were evaluated. One hundred twenty-seven consecutive patients in 1 center were treated with a novel attenuated-dose sunitinib regimen (37.5 mg/d, 6-week cycle: 4 weeks of treatment, then 2 weeks of no treatment) with outcomes captured in a prospective registry. Efficacy and safety outcomes of these patients were compared against those who received sunitinib at conventional dosing (n = 33) at all 4 centers. Statistical modeling was adjusted for baseline prognostic criteria and therapy line where possible. RESULTS: Overall survival from treatment initiation (OSinitiation), overall survival from the first documented metastasis (OStotal), and progression-free survival (PFS) were similar for patients who received first-line sunitinib for conventional relative to attenuated dose regimens (OSinitiation: 18.3 vs. 16.5 months, respectively; P = .54; OStotal: 27.4 vs. 21.8 months, respectively; P = .45; PFS: 6.7 vs. 7.9 months, respectively; P = .64), similar to real-world outcomes in Western studies. A marked lower rate of severe toxicities, dose delays, and reductions were observed with the attenuated dose regimen, with 75/127 (59%), rather than 28/33 (85%) for the conventional dose arm who experienced Grade ≥ 3 toxicities (P = .0088); 31/127 (24%) rather than 19/33 (58%) who experienced dose delays (P = .0004); and 44/127 (35%) rather than 23/33 (70%) who experienced dose reduction (P = .0005) during their course of treatment. CONCLUSION: An attenuated dose regimen of sunitinib yielded comparable real-world efficacy outcomes, with considerable reduction in toxicities as documented in a prospective registry.

A phase II study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 86-9766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma.

PURPOSE: There is an unmet need for treatment options in hepatocellular carcinoma (HCC). Sorafenib is currently the only approved systemic treatment for HCC. Refametinib, an oral, allosteric MEK inhibitor, has demonstrated antitumor activity in combination with sorafenib in vitro and in vivo. A phase II study evaluated efficacy and safety of refametinib plus sorafenib in Asian patients with HCC (NCT01204177). EXPERIMENTAL DESIGN: Eligible patients received twice-daily refametinib 50 mg plus twice-daily sorafenib 200 mg (morning)/400 mg (evening), with dose escalation to sorafenib 400 mg twice daily from cycle 2 if no grade ≥ 2 hand-foot skin reaction, fatigue, or gastrointestinal toxicity occurred. Primary efficacy endpoint: disease control rate. Secondary endpoints: time to progression, overall survival, pharmacokinetic assessment, biomarker analysis, safety, and tolerability. RESULTS: Of 95 enrolled patients, 70 received study treatment. Most patients had liver cirrhosis (82.9%) and hepatitis B viral infection (75.7%). Disease control rate was 44.8% (primary efficacy analysis; n = 58). Median time to progression was 122 days, median overall survival was 290 days (n = 70). Best clinical responders had RAS mutations; majority of poor responders had wild-type RAS. Most frequent drug-related adverse events were diarrhea, rash, aspartate aminotransferase elevation, vomiting, and nausea. Dose modifications due to adverse events were necessary in almost all patients. CONCLUSIONS: Refametinib plus sorafenib showed antitumor activity in patients with HCC and was tolerated at reduced doses by most patients. Frequent dose modifications due to grade 3 adverse events may have contributed to limited treatment effect. Patients with RAS mutations appear to benefit from refametinib/sorafenib combination.

Synovial sarcoma of the kidney: a report of 4 cases with pathologic appraisal and differential diagnostic review.

BACKGROUND: Synovial sarcoma of the kidney is rare. It is clinicoradiologically indistinguishable from the more frequently encountered renal cell carcinoma. Histologically it needs to be differentiated from other spindle cell lesions occurring within the kidney, including a spectrum of benign to malignant tumors. Among malignant spindle cell tumors of the kidney, mimics of synovial sarcoma are sarcomatoid renal cell carcinoma, sarcomatoid urothelial carcinoma and other primary sarcomas, such as leiomyosarcoma and malignant fibrous histiocytoma. CASES: Four cases of synovial sarcoma originated in the kidney, with this report focusing on clinicopathologic and differential diagnostic features. CONCLUSION: The correct diagnosis of synovial sarcoma requires support by an immunohistochemical panel as well as adjunctive investigations like polymerase chain reaction and fluorescence in situ hybridization to determine the presence of the SYT-SSX fusion gene and translocation (X,18), respectively.

A unique pair of monozygotic twins with concordant clear cell renal cell carcinoma: a case report.

INTRODUCTION: Genetic predisposition to clear cell renal cell carcinoma (ccRCC) has been linked to disorders such as von Hippel-Lindau (VHL) syndrome. While twin research is a classic approach for elucidating genetic and environmental contributions to disease, no monozygotic twin-pair concordant for ccRCC in the absence of VHL syndrome has been previously reported in the literature or in major twin registries. CLINICAL PICTURE: We describe a unique monozygotic twin-pair concordant for ccRCC, with discordant but early ages of onset of 25 and 38 respectively. Cytogenetic studies and direct sequencing for VHL gene mutations in the second twin proved unremarkable. CONCLUSIONS: This is the fi rst reported case of monozygotic twins concordant for ccRCC in the absence of VHL gene mutation. The early yet discordant, age of onset of disease in both twins suggests both genetic and environmental contributions to ccRCC.

Triplet combination of gemcitabine, paclitaxel, and carboplatin followed by maintenance 5-fluorouracil and folinic acid in patients with metastatic nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a disease that is highly responsive to various chemotherapeutic agents. In the metastatic setting, 2-drug combination chemotherapy generally provides a response rate of 55% to 75%, and median survival of 10 to 12 months. The objective of the current study was to assess the efficacy of a 3-drug combination followed by maintenance treatment in patients with metastatic NPC. METHODS: Patients with metastatic NPC were treated with a combination of gemcitabine at a dose of 1,000 mg/m(2), paclitaxel at a dose of 70 mg/m(2), and carboplatin at an area under the concentration-time-curve (AUC) of 2.5 on Days 1 and 8 every 21 days. Patients who achieved partial or complete response continued to receive weekly 5-fluorouracil at a dose of 450 mg/m(2) and leucovorin at a dose of 30 mg/m(2) for 48 weeks. RESULTS: Twenty-eight patients were recruited. Twenty-two (79%) patients had >or=2 sites of disease. Toxicities were mainly from bone marrow suppression, with 79% grade 3/4 neutropenia, 32% grade 3/4 anemia, and 29% grade 3/4 thrombocytopenia (according to the National Cancer Institute Common Toxicity Criteria). The overall response rate to the 3-drug regimen was 86%, with a complete response rate of 11%. The median duration of response was 8 months and the median overall survival was 22 months. CONCLUSIONS: This regimen of a 3-drug combination followed by maintenance is feasible and has demonstrated an encouraging response rate and overall survival.

Is there a role for platinum chemotherapy in the treatment of patients with hormone-refractory prostate cancer?

Docetaxel chemotherapy is the current standard of care for metastatic hormone-refractory prostate cancer (HRPC). Platinum chemotherapy drugs, such as cisplatin and carboplatin, have moderate single-agent activity in HRPC. Next-generation platinum drugs, including satraplatin and oxaliplatin, may have additional activity in the management of HRPC. Furthermore, neuroendocrine differentiation may play a role in disease progression, providing a rationale for platinum-based chemotherapy in the management of HRPC. The authors reviewed the MEDLINE database for reports related to platinum-based chemotherapy in patients with advanced prostate cancer and evaluated studies that reviewed the role of neuroendocrine differentiation in the progression of HRPC. Older studies from the 1970s and 1980s suggested a lack of activity of cisplatin and carboplatin; however, those studies were flawed at least in part by their methods of response assessment. More recent Phase II studies of carboplatin suggested a moderate level of clinical and palliative activity when it was used as a single agent. However, when carboplatin was combined with a taxane and estramustine, high response rates were observed in several recent clinical trials. In addition, a randomized trial suggested that satraplatin plus prednisone improved progression-free survival compared with prednisone alone. For patients who progressed after docetaxel, no standard options existed in the literature that was reviewed. Several preliminary reports suggested that carboplatin and oxaliplatin may have activity as second-line chemotherapy. Platinum chemotherapy drugs historically have been considered inactive in HRPC, although a review of the data suggested otherwise. Carboplatin, in particular, induced very high response rates when it was combined with estramustine and a taxane, but it also appeared to have activity in patients who progressed after docetaxel. Satraplatin plus prednisone is being investigated in a large Phase III trial as second-line chemotherapy for HRPC. Targeting neuroendocrine cells may provide a new therapeutic approach to HRPC.

A randomized phase II trial of single-agent gemcitabine, vinorelbine, or docetaxel in patients with advanced non-small cell lung cancer who have poor performance status and/or are elderly.

BACKGROUND: Patients with poor performance status and/or are elderly are frequently considered a compromised group at high risk of chemotherapy-related morbidities and less likely to benefit from treatment. We aimed to evaluate tolerability and efficacy of three single-agent regimens in these patients. PATIENTS AND METHODS: Patients with advanced non-small cell lung cancer who had performance status 2/3 and/or were aged 70 and older were randomly assigned to receive gemcitabine, vinorelbine, or docetaxel. Objective response, toxicities, and quality of life were evaluated. RESULTS: One hundred thirty-five patients were registered, of whom one was ineligible. Of the 134 patients, 43 received gemcitabine, 45 vinorelbine, and 46 docetaxel. The response rate was 16%, 20%, 22% for gemcitabine, vinorelbine, and docetaxel, respectively. The main grade 3/4 toxicities were fatigue (18%) and neutropenia (16%). There was improvement in global health scores, cough, and dyspnea for all treatment groups. The improvement in dyspnea was most marked in patients with performance status 3. CONCLUSION: There was no significant advantage of any of the treatment arms over the rest. There was benefit seen with improvement of quality of life in patients who were able to receive more cycles of chemotherapy.

Paclitaxel, carboplatin, and gemcitabine in metastatic nasopharyngeal carcinoma: a Phase II trial using a triplet combination.

BACKGROUND: Patients with nasopharyngeal carcinoma (NPC) are treated primarily with radiotherapy. In the disseminated state, platinum-based, 2-drug combination regimens yielded response rates of 55-75%, achieving a median survival of 10-12 months. With the proven efficacy of second-generation cytotoxics like paclitaxel and gemcitabine in patients with metastatic NPC, the authors hypothesized that a triplet combination incorporating these newer cytotoxics may improve treatment results. METHODS: Thirty-two patients with metastatic NPC were treated with combination chemotherapy that included paclitaxel 70 mg/m(2) on Days 1 and 8, carboplatin dosed to area under curve of 5 on Day 1, and gemcitabine 1000 mg/m(2) on Days 1 and 8 every 21 days for a maximum of 8 cycles. RESULTS: Two patients achieved a complete response, and 23 patients achieved a partial response, for an overall response rate of 78%. The main toxicities were hematologic, with 41% of patients experiencing Grade 3 or 4 anemia, 41% of patients experiencing Grade 3 or 4 thrombocytopenia, and 78% of patients experiencing Grade 3 or 4 neutropenia. The median time to disease progression was 8.1 months, and the median overall survival was 18.6 months. CONCLUSIONS: The combination of paclitaxel, carboplatin, and gemcitabine showed promising efficacy against metastatic NPC but at the expense of considerable toxicity.

Order effects in the assessment of quality of life in cancer patients.

Methodological studies and outcome research often include several health-related quality of life (HRQoL) measurement scales in one questionnaire. Psychological studies have previously demonstrated that changing the sequential order of measurement scales within a questionnaire can alter the pattern of responses. Little is known, however, about whether there are order effects on the assessment of HRQoL in cancer patients. Here we address this issue in a study of 190 Singaporean cancer patients who were assessed using two different HRQoL instruments placed in alternating sequence within a questionnaire package. Measurement properties of the instruments, including the number of missing values, means, variability, known-group validity and internal consistency, were compared in the two samples representing different presentation orders. The HRQoL instruments administered in different sequential orders appeared to be equivalent in several aspects. No major effect of presentation order on outcomes was shown. The reasons and implications of the absence of an order effect are discussed. We conclude that presentation order is unlikely to alter the responses to the two HRQoL instruments.

Radical prostatectomy lowers plasma vascular endothelial growth factor levels in patients with prostate cancer.

OBJECTIVES: To measure the change in plasma vascular endothelial growth factor (VEGF) levels after radical prostatectomy (RP) and to examine the association of pre-RP VEGF levels with known prognostic factors. METHODS: Plasma was collected from patients in two separate cohorts. The first cohort included 86 patients who consented to give blood before and after RP. The second cohort consisted of 280 plasma samples, obtained from untreated patients with clinically localized prostate cancer. Plasma VEGF levels were measured by enzyme-linked immunosorbent assay. The change in plasma VEGF before and 6 to 8 weeks after RP was analyzed using a Wilcoxon signed rank test. The associations between the pre-RP VEGF levels and prognostic factors were assessed with the Spearman correlation coefficient and the Kruskal-Wallis test. RESULTS: In a cohort of 86 patients with clinically localized prostate cancer, the median preoperative VEGF level was 49.8 pg/mL. The median level 1 month after surgery was significantly lower at 39.1 pg/mL (P = 0.006, 20% decrease). A repeat analysis 6 months or more after surgery demonstrated that the percentage of decrease in the plasma VEGF levels persisted. Plasma VEGF levels were also measured in a separate cohort of 280 patients with localized prostate cancer and demonstrated no statistically significant association with risk groups or known tumor-associated prognostic factors. CONCLUSIONS: These results suggest that the prostate gland itself may be a significant source of systemic VEGF and raises the possibility that elevated plasma VEGF levels could be a reflection of prostatic VEGF production.