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1.
Ann Oncol ; 31(2): 257-265, 2020 02.
Article in English | MEDLINE | ID: mdl-31959342

ABSTRACT

BACKGROUND: Radium-223 prolongs overall survival and delays symptomatic skeletal events (SSEs) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. The approved radium-223 regimen is 55 kBq/kg every 4 weeks (q4w) for six cycles (standard dose). We investigated different radium-223 regimens in patients with mCRPC. PATIENTS AND METHODS: Patients were randomised 1 : 1 : 1 to radium-223 standard-dose, high-dose (88 kBq/kg q4w for six cycles) or extended-schedule arms (55 kBq/kg q4w for 12 cycles). The primary end point, SSE-free survival (SSE-FS), was compared in patients treated with a high- versus standard-dose regimen, or with a standard dose in an extended (>6 to 12 cycles) versus standard schedule (six cycles). RESULTS: A total of 391 patients were randomised; baseline characteristics were balanced between arms. On-treatment SSEs developed in 37/130 (28%), 42/130 (32%) and 48/131 (37%) patients in the standard-dose, high-dose and extended-schedule arms, respectively. There was no statistically significant difference in SSE-FS in the high- versus standard-dose arms [median 12.9 months versus 12.3 months; hazard ratio (HR) 1.06, 80% confidence interval (CI) 0.88-1.27, P = 0.70], and in the extended- versus standard-schedule arms (median 10.8 months versus 13.2 months; HR 1.26, 80% CI 0.94-1.69, P = 0.31). Overall survival in the three treatment arms was similar. As many as 370 (95%) patients received treatment (median of six cycles) in each arm. Grade ≥3 treatment-emergent adverse events (TEAEs) affected 34% of patients in the standard-dose, 48% in the high-dose and 53% in the extended-schedule arm, causing permanent discontinuation in 9%, 16% and 17% of patients, respectively. CONCLUSION: Radium-223 high-dose or extended-schedule regimens resulted in no change in SSE-FS or other efficacy end points and were associated with more grade ≥3 TEAEs. The extended-schedule regimen (beyond six doses) could not be implemented in a large proportion of patients due to disease progression. Therefore, the standard-dose schedule remains one of the standard therapies for patients with symptomatic mCRPC. TRIAL REGISTRATION: ClinicalTrials.govNCT02023697.


Subject(s)
Bone Neoplasms , Prostatic Neoplasms, Castration-Resistant , Radium , Bone Neoplasms/drug therapy , Bone Neoplasms/radiotherapy , Humans , Male , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/radiotherapy , Radioisotopes , Radium/adverse effects
2.
Intern Med J ; 45(6): 666-9, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26059878

ABSTRACT

Autoimmune thrombocytopenia is an uncommon but reported paraneoplastic manifestation of renal cell carcinoma (RCC). Treatment usually involves management of the underlying malignancy; however, steroids have shown a benefit in published case reports. Here, we describe a patient with profound thrombocytopenia secondary to metastatic RCC. It was refractory to steroid and intravenous immunoglobulin, but the platelet count improved markedly following initiation of everolimus. The possible explanation includes immunomodulation, tumour lysis or a combination of both effects. This is the first reported case of everolimus used in paraneoplastic thrombocytopenia from RCC. More studies are needed for further investigation of its potential use in secondary immune thrombocytopenia from RCC and perhaps other malignancies.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Everolimus/therapeutic use , Kidney Neoplasms/drug therapy , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Aged , Carcinoma, Renal Cell/complications , Carcinoma, Renal Cell/diagnosis , Humans , Kidney Neoplasms/complications , Kidney Neoplasms/diagnosis , Male , Purpura, Thrombocytopenic, Idiopathic/complications , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Treatment Outcome
3.
Prostate Cancer Prostatic Dis ; 17(2): 105-11, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24686773

ABSTRACT

BACKGROUND: The optimal hormone treatment strategy in prostate cancer is uncertain, particularly in patients with metastatic disease. We aimed to compare the relative benefits and harms of intermittent androgen deprivation (IAD) to continuous androgen deprivation (CAD) in all stages of prostate cancer. METHODS: We included eight randomised control trials (4668 patients) in our systematic review and meta-analysis. Median follow-up ranged from 29 to 118 months. Pooled hazard ratios (HRs) were calculated for overall survival (OS), cancer-specific survival, time to cancer progression and mortality unrelated to prostate cancer. The relative effect of treatment in patients with metastatic and those with non-metastatic disease was compared using pre-planned subgroup analysis. RESULTS: There was no difference in OS between patients treated with IAD and CAD (HR 1.01, 95% confidence interval (CI) 0.93-1.10); nor was there any difference in cancer-specific survival (HR 1.03; 95% CI 0.88-1.21). There was a non-significant trend towards longer time to prostate cancer progression for IAD (HR 0.93, 95% CI 0.84-1.04), raising the possibility of slower selection for castrate resistance. There was no significant difference in OS when analysis was restricted to patients with metastatic disease (HR 1.04, 95% CI 0.91-1.19) or patients without metastatic disease (HR 1.06, 95% CI 0.91-1.23) (test for subgroup differences P=0.84). Most studies found an improvement in quality of life or toxicity profile with IAD. CONCLUSIONS: IAD is non-inferior to CAD in terms of OS and cancer-specific survival, and is at least non-inferior in terms of time to progression. This meta-analysis confirms IAD as a valid standard of care for managing prostate cancer patients.


Subject(s)
Androgen Antagonists/therapeutic use , Androgens/metabolism , Prostatic Neoplasms/drug therapy , Antineoplastic Agents, Hormonal/therapeutic use , Disease Progression , Humans , Male , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Randomized Controlled Trials as Topic , Treatment Outcome
4.
Curr Oncol ; 21(1): e151-4, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24523613

ABSTRACT

Mismatch-repair-deficient colorectal cancers often contain kinase-activating V600E BRAF mutations, but no clinical utility has yet been demonstrated in this setting for monotherapy using oral braf kinase inhibitors such as vemurafenib or dabrafenib. Recent studies have indicated that tumour resistance to braf inhibition is mediated by upregulated epidermal growth factor receptor (egfr) signalling, disruption of which is a routine treatment strategy in KRAS wild-type colorectal cancer. In this report, we describe the clinical course of a heavily pretreated patient who elected to receive off-label dual-targeted braf- and egfr-inhibitory therapy with good tolerance and apparent clinical benefit.

5.
Clin. transl. oncol. (Print) ; 15(11): 865-870, nov. 2013.
Article in English | IBECS | ID: ibc-127667

ABSTRACT

The completion of the human genome sequence sparked optimism about prospects for new anticancer drug development, but clinical progress over the last decade has proven slower than expected. Here it is proposed that unrealistically high expectations of first-generation discovery-based diagnostics have contributed to this problem. Hypothesis-based single-molecule tests (e.g., mutation screening of KRAS, EGFR, BRAF or KIT genes) continue to change clinical practice incrementally, whereas first-generation multiplex assays--such as gene expression profiling and proteomics--have identified few high-impact therapeutic targets despite numerous correlations with prognosis. To move forward, second-generation multiplex diagnostics should be based not on statistical patterns/associations alone, but on clinically interpretable ('high-signal-to-noise') data such as change-of-function mutations, gene amplifications, recurrent chromosomal anomalies, and abnormal phosphorylation profiles of ERK or mTOR signaling cascades (AU)


Subject(s)
Humans , Male , Female , Genome, Human/genetics , Genome, Human/radiation effects , Proteomics/methods , DNA Mutational Analysis/adverse effects
6.
Clin Transl Oncol ; 15(11): 865-70, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24002944

ABSTRACT

The completion of the human genome sequence sparked optimism about prospects for new anticancer drug development, but clinical progress over the last decade has proven slower than expected. Here it is proposed that unrealistically high expectations of first-generation discovery-based diagnostics have contributed to this problem. Hypothesis-based single-molecule tests (e.g., mutation screening of KRAS, EGFR, BRAF or KIT genes) continue to change clinical practice incrementally, whereas first-generation multiplex assays--such as gene expression profiling and proteomics--have identified few high-impact therapeutic targets despite numerous correlations with prognosis. To move forward, second-generation multiplex diagnostics should be based not on statistical patterns/associations alone, but on clinically interpretable ('high-signal-to-noise') data such as change-of-function mutations, gene amplifications, recurrent chromosomal anomalies, and abnormal phosphorylation profiles of ERK or mTOR signaling cascades.


Subject(s)
Biomarkers, Tumor/genetics , Biomedical Research , Mutation/genetics , Neoplasms/diagnosis , Neoplasms/genetics , Humans , Neoplasms/therapy , Predictive Value of Tests
7.
QJM ; 106(6): 517-21, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23596265

ABSTRACT

BACKGROUND: Occupational factors have long been linked to patterns of mortality. AIM: Based on the premiss that an obituary in The New York Times (NYT) tends to imply success in one's vocation, we used NYT obituary data to elucidate the relationships between career success, terminal disease frequency and longevity. DESIGN: One thousand consecutive obituaries published in NYT over the period 2009-11 were analysed in terms of gender, occupation and terminal disease, as attributed. METHODS: The frequency of disease for each occupational category was determined, and the mean age of death was calculated for each disease and occupational subgroup. RESULTS: Male obituaries outnumbered female (813 vs. 186), and the mean age of death was higher for males than females (80.4 ± 0.4 vs. 78.8 ± 1.1 years). Younger ages of death were evident in sports players (77.4 years), performers (77.1) and creative workers (78.5), whereas older deaths were seen in military (84.7), business (83.3) and political (82.1) workers. Younger deaths were more often associated with accidents (66.2 years), infection (68.6) and organ-specified cancers (73.0). 'Old age' was more often the cited cause of death for philanthropists, academics and doctors, and less often for sportsmen, performers and creatives. Cancer deaths occurred most often in performers and creatives, with lung cancer commonest among performers and least common in professionals. CONCLUSION: Fame and achievement in performance-related careers may be earned at the cost of a shorter life expectancy. In such careers, smoking and other risk behaviours may be either causes or effects of success and/or early death.


Subject(s)
Life Expectancy , Newspapers as Topic/statistics & numerical data , Occupations/statistics & numerical data , Aged , Aged, 80 and over , Cause of Death , Female , Humans , Lung Neoplasms/mortality , Male , Sex Distribution , United States/epidemiology
8.
Med Oncol ; 29(3): 1536-42, 2012 Sep.
Article in English | MEDLINE | ID: mdl-21983862

ABSTRACT

Primary breast invasive ductal carcinoma coexisting with ductal carcinoma in situ (IDC-DCIS) is characterized by lower proliferation rate and metastatic propensity than size-matched pure IDC. IDC-DCIS is also more often ER-positive, PR-positive and/or HER2-positive. This analysis aims to clarify whether the presence of coexisting DCIS in IDC affects tumor aggressiveness in various biological subtypes of breast cancer, respectively. Tumor data obtained from 1,355 consecutive female patients undergoing upfront surgery for primary breast cancer were analyzed retrospectively; 196 patients with pure DCIS were excluded. Based on evidence that immunohistochemistry (IHC) provides a reasonable approximation of molecular phenotypes, the tumor samples were divided into 4 groups: (1) luminal A (ER and/or PR-positive, HER2-negative, Ki67 ≤ 12), (2) luminal B (ER and/or PR-positive, HER2-negative, Ki67 > 12), (3) HER2 (HER2-positive) and (4) basal-like (triple-negative) disease. Ki67 expression and nodal involvement of IDC with or without DCIS in these groups were compared. The number of patients with luminal A, luminal B, HER2 and basal-like breast cancer were 396, 265, 258 and 117, respectively. Ki-67 was lower in IDC-DCIS than in size-adjusted pure IDC of both luminal A and luminal B subtypes (P = 0.15 and <0.005, respectively). In HER2 or basal-like tumors, there were no significant difference between pure IDC and IDC-DCIS. The presence of coexisting DCIS in IDC predicts lower biological aggressiveness in luminal cancers but not in the conventionally more aggressive HER2-positive and triple-negative subtypes.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Neoplasms, Multiple Primary/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Lymphatic Metastasis/pathology , Middle Aged , Neoplasm Invasiveness/pathology , Retrospective Studies
9.
Ann Oncol ; 23(3): 610-617, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21700731

ABSTRACT

BACKGROUND: This phase II study evaluated single-agent bosutinib in pretreated patients with locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Patients received oral bosutinib 400 mg/day. The primary end point was the progression-free survival (PFS) rate at 16 weeks. Secondary end points included objective response rate, clinical benefit rate, 2-year overall survival rate, safety, and changes in levels of bone resorption/formation biomarkers. RESULTS: Seventy-three patients were enrolled and treated. Median time from diagnosis of metastatic disease to initiation of bosutinib treatment was 24.5 months. For the intent-to-treat population, the PFS rate at 16 weeks was 39.6%. Unexpectedly, all responding patients (n = 4) were hormone receptor positive. The clinical benefit rate was 27.4%. The 2-year overall survival rate was 26.4%. The main toxic effects were diarrhea (66%), nausea (55%), and vomiting (47%). Grade 3-4 laboratory aminotransferase elevations occurred in 14 (19%) patients. Myelosuppression was minimal. No consistent changes in the levels of bone resorption/formation biomarkers were seen. CONCLUSIONS: Bosutinib showed promising efficacy in prolonging time to progression in chemotherapy-pretreated patients with locally advanced or metastatic breast cancer. Bosutinib was generally well tolerated, with a safety profile different from that of the Src/Abl tyrosine kinase inhibitor dasatinib in a similar patient population.


Subject(s)
Aniline Compounds/therapeutic use , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Nitriles/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Quinolines/therapeutic use , Salvage Therapy/methods , Adult , Aged , Bone Remodeling/drug effects , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Metastasis/drug therapy , Neoplasm Staging , Protein-Tyrosine Kinases/antagonists & inhibitors
10.
Asian Pac J Cancer Prev ; 12(8): 2093-6, 2011.
Article in English | MEDLINE | ID: mdl-22292657

ABSTRACT

BACKGROUND: The affordability of diagnostic, preventive and therapeutic interventions is a global concern, particularly in the developing world. To clarify the educational and financial factors that influence purchasing decisions, we conducted a survey of Hong Kong cancer patients across a broad social spectrum. METHODS: A questionnaire was designed to assess the effect of costs on purchasing decisions relating to six drug-related variables: efficacy, tolerability, convenience, safety, peer pressure, and uncertainty. Validation of the original 31-part survey resulted in a final set of 22 core questions that was administered to 51 consecutive oncology patients who were characterized in terms of varying household income and educational level. RESULTS: Most respondents (87.6%) were Hong Kong-born or mainland Chinese. There was a strong correlation between household income and education. Demand for drug tolerability and safety was high and cost-inelastic across all educational and income groups. An unexpected finding was that patients from low-income/education households were keen to purchase costly medications (whether Western, or Chinese herbs) of reputed high efficacy, whereas patients from middle-income/-education backgrounds were more negatively influenced by considerations of cost. Only the most affluent and well-educated patients valued overall survival above disease-free survival when making drug purchasing decisions; this cohort was also the least influenced by peer pressure, and the most willing to pay extra for drugs offering more convenience alone. CONCLUSION: Low-income/education Asian patients had paradoxically high expectations of costly drug interventions. Although larger studies addressing this issue are needed to confirm these conclusions, public education initiatives aimed at protecting low-income/education patients from exploitation or disappointment may be desirable.


Subject(s)
Antineoplastic Agents/economics , Decision Making , Educational Status , Income/statistics & numerical data , Neoplasms/drug therapy , Neoplasms/economics , Asian People , Cohort Studies , Disease-Free Survival , Drug Costs , Hong Kong , Humans , Pilot Projects , Poverty , Socioeconomic Factors , Surveys and Questionnaires
11.
Br J Cancer ; 102(9): 1391-6, 2010 Apr 27.
Article in English | MEDLINE | ID: mdl-20424617

ABSTRACT

BACKGROUND: The metastatic propensity of invasive ductal carcinoma (IDC) of the breast correlates with axillary node involvement and with expression of the proliferation antigen Ki-67, whereas ductal carcinoma in situ (DCIS) is non-metastasising. To clarify whether concomitant DCIS affects IDC prognosis, we compared Ki-67 expression and node status of size-matched IDC subgroups either with DCIS (IDC-DCIS) or without DCIS (pure IDC). METHODS: We analysed data from 1355 breast cancer patients. End points were defined by the association of IDC (with or without DCIS) with grade, nodal status, Ki-67, and ER/HER2. RESULTS: Size-matched IDC-DCIS was more likely than pure IDC to be screen detected (P=0.03), to occur in pre-menopausal women (P=0.002), and to be either ER-positive (P=0.002) or HER2-positive (P<0.0005), but less likely to be treated with breast-conserving surgery (P=0.004). Grade and Ki-67 were lower in IDC-DCIS than in pure IDC (P=0.02), and declined as the DCIS enlarged (P<0.01). Node involvement and lymphovascular invasion in IDC-DCIS increased with the size ratio of IDC to DCIS (P<0.01). A 60-month cancer-specific survival favoured IDC-DCIS over size-matched pure IDC (97.4 vs 96.0%). CONCLUSION: IDC co-existing with DCIS is characterised by lower proliferation and metastatic potential than size-matched pure IDC, especially if the ratio of DCIS to IDC size is high. We submit that IDC-DCIS is biologically distinct from pure IDC, and propose an incremental molecular pathogenesis of IDC-DCIS evolution involving an intermediate DCIS precursor that remains dependent for replication on upstream mitogens.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal/pathology , Neoplasm Invasiveness , Adult , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Carcinoma in Situ/pathology , Carcinoma, Ductal/mortality , Carcinoma, Ductal/surgery , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Ki-67 Antigen/analysis , Ki-67 Antigen/genetics , Lymphatic Metastasis , Middle Aged , Neoplasm Metastasis , Postmenopause , Premenopause , Receptor, ErbB-2/analysis , Receptors, Estrogen/analysis , Receptors, Estrogen/genetics , Receptors, Progesterone/analysis , Receptors, Progesterone/genetics , Survival Rate , Survivors
12.
Br J Cancer ; 102(6): 981-6, 2010 Mar 16.
Article in English | MEDLINE | ID: mdl-20160718

ABSTRACT

BACKGROUND: Molecularly targeted agents with anti-angiogenic activity, including bevacizumab, have demonstrated clinical activity in patients with advanced/metastatic hepatocellular carcinoma (HCC). This multicentre phase II study involving patients from several Asian countries sought to evaluate the safety and efficacy of bevacizumab plus capecitabine in this population. METHODS: Histologically proven/clinically diagnosed advanced HCC patients received bevacizumab 7.5 mg kg(-1) on day 1 and capecitabine 800 mg m(-2) twice daily on days 1-14 every 3 weeks as first-line therapy. RESULTS: A total of 45 patients were enrolled; 44 (96%) had extrahepatic metastasis and/or major vessel invasion and 30 (67%) had hepatitis B. No grade 3/4 haematological toxicity occurred. Treatment-related grade 3/4 non-haematological toxicities included diarrhoea (n=2, 4%), nausea/vomiting (n=1, 2%), gastrointestinal bleeding (n=4, 9%) and hand-foot syndrome (n=4, 9%). The overall response rate (RECIST) was 9% and the disease control rate was 52%. Overall, median progression-free survival (PFS) and overall survival (OS) were 2.7 and 5.9 months, respectively. Median PFS and OS were 3.6 and 8.2 months, respectively, for Cancer of the Liver Italian Programme (CLIP) score < or =3 patients, and 1.4 and 3.3 months, respectively, for CLIP score 4 patients. CONCLUSION: The bevacizumab-capecitabine combination shows good tolerability and modest anti-tumour activity in patients with advanced HCC.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Liver Neoplasms/drug therapy , Adult , Aged , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab , Capecitabine , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Disease Progression , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Survival Analysis , Treatment Outcome , Young Adult
13.
Perspect Biol Med ; 52(1): 116-25, 2009.
Article in English | MEDLINE | ID: mdl-19168949

ABSTRACT

The end of the human race is not imminent, but it is both inevitable and important. Judging by the scarcity of relevant publications, however, there seems little public or professional concern about this prospect. We submit that this striking disinterest reflects a combination of ignorance and denial that is putting the long-term interests of society in jeopardy. With the pace of change now outstripping that of adaptation, it is no longer alarmist for academics to raise awareness about the approach of human extinction and to design strategies by which time to extinction might be prolonged. By making complacent and anthropocentric thinking less politically correct than it is at present, such awareness could motivate the world community to reformulate social norms in a way that benefits our descendants as much as possible for as long as possible.


Subject(s)
Biological Evolution , Extinction, Biological , Anthropology , Consciousness , Genome, Human , Humans , Models, Theoretical
14.
Infect Genet Evol ; 9(2): 283-5, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19073283

ABSTRACT

Beta-lactam-resistant staphylococci evolved due to widespread nosocomial antibiotic use during the twentieth century, but the last decade has seen the emergence of genotypically distinct resistant bacteria outside hospitals, such as community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). This changing epidemiology suggests that mechanisms other than direct antibiotic selection could be involved in the spread of bacterial resistance. Here we report a 17% prevalence of methicillin-resistant Staphylococcus intermedius (MRSI)-a markedly higher rate than the 0-2% reported in some other series-in a random sample of nasal swabs from healthy pet dogs in Hong Kong. In contrast, MRSA was not detected. Since the mecA mobile genetic element responsible for methicillin resistance has been shown by others to be horizontally transmissible between dogs and humans, our findings suggest that the high prevalence of this resistance vector in companion species is a legitimate concern for public health, and raise the important possibility that pet-acquired methicillin-resistant staphylococci (PA-MRS) could play a role in zoonotic mecA gene spread.


Subject(s)
Community-Acquired Infections/microbiology , Disease Reservoirs , Dogs/microbiology , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Staphylococcal Infections/microbiology , Animals , Anti-Bacterial Agents/pharmacology , Community-Acquired Infections/epidemiology , Hong Kong/epidemiology , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Prevalence , Staphylococcal Infections/epidemiology
16.
Ann Surg Oncol ; 15(9): 2500-5, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18581185

ABSTRACT

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a notoriously aggressive malignancy associated with a highly lethal clinical course despite therapeutic intervention. Our present study attempts to identify factors that could potentially improve therapeutic strategies by analyzing the clinicopathological features, treatment and outcome of ATC patients managed over the past four decades at our institution. METHODS: Fifty patients with biopsy-proven ATC during the period 1966 to 2006 were studied. All patients were managed with surgery, radiotherapy, chemotherapy and/or chemoradiation. Survival was calculated by the Kaplan-Meier method. Potential factors affecting survival were compared by the log rank test. RESULTS: Most patients (88%) presented with a neck mass; 17 patients (34%) also had cervical lymphadenopathy. Distant metastases were clinically present in 9 (18%). Median survival was 97 days, whereas the 1- and 3-year survival was 14% and 8%, respectively. On univariate analysis, patients aged

Subject(s)
Carcinoma/mortality , Carcinoma/therapy , Thyroid Neoplasms/mortality , Thyroid Neoplasms/therapy , Thyroidectomy , Adult , Aged , Aged, 80 and over , Carcinoma/pathology , Carcinoma/radiotherapy , Carcinoma/surgery , Combined Modality Therapy , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Survival Rate , Thyroid Neoplasms/pathology , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery , Treatment Outcome
17.
Aliment Pharmacol Ther ; 27(11): 997-1005, 2008 Jun 01.
Article in English | MEDLINE | ID: mdl-18363897

ABSTRACT

BACKGROUND: The field of colorectal cancer chemotherapy has been transformed by the advent of molecule-specific drugs. Combined use of such drugs enhances tumour response rates, but controlled data quantifying the relative efficacy and cost-effectiveness of different drug combinations on overall survival remain scarce. AIM: To conduct an overview of published clinical trials in advanced colorectal cancer, with the objective of framing provisional approaches to current management. METHODS: An NCBI/PubMed search was performed using the strings, 'colorectal cancer' ('metastatic' or 'advanced' or 'palliative') and ('chemotherapy' or 'drug therapy' or 'targeted' or 'target-specific' or 'molecularly-targeted'). RESULTS: Combinations of target-specific drugs (with or without the DNA-alkylating agent oxaliplatin) have substantially enhanced colorectal cancer time to progression over the last decade and have also expedited surgical resection of liver metastases. Disease-free survival, overall survival and quality of life are favourably influenced. CONCLUSIONS: Target-specific drugs improve palliative efficacy in the setting of advanced colorectal cancer. However, key issues persist as to the cost-effectiveness of these newer drug treatments, and further controlled trials are needed to resolve this important debate.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Antineoplastic Agents/economics , Antineoplastic Combined Chemotherapy Protocols/economics , Chemotherapy, Adjuvant , Clinical Trials as Topic , Cost-Benefit Analysis , Drug Delivery Systems , Humans
18.
Cancer Chemother Pharmacol ; 62(6): 1111-2, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18283460

ABSTRACT

Targeted inhibition of epidermal growth factor receptors (EGFR) is becoming a standard anticancer treatment in defined clinical scenarios. EGFR inhibition may be achieved either by small-molecule orally bioavailable tyrosine kinase inhibitors, such as gefitinib or erlotinib, or else by large-molecule receptor antibodies, such as cetuximab or panitumumab. Here, we describe a case of pancreatic cancer in which the small-molecule EGFR antagonist erlotinib was used before and after the EGFR antibody cetuximab, with unexpected potentiation of both toxic and therapeutic sequelae.


Subject(s)
Adenocarcinoma/drug therapy , Antibodies, Monoclonal/pharmacology , ErbB Receptors/antagonists & inhibitors , Neoplasm Proteins/antagonists & inhibitors , Pancreatic Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Quinazolines/pharmacology , Adenocarcinoma/enzymology , Adenocarcinoma/secondary , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Biomarkers, Tumor/blood , Bone Neoplasms/drug therapy , Bone Neoplasms/enzymology , Bone Neoplasms/secondary , Cetuximab , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Drug Eruptions/etiology , Drug Interactions , Drug Resistance, Neoplasm , Erlotinib Hydrochloride , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/enzymology , Lung Neoplasms/secondary , Lymphatic Metastasis , Middle Aged , Pancreatic Neoplasms/enzymology , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/pharmacology , Quinazolines/administration & dosage , Quinazolines/adverse effects , Gemcitabine
19.
Cancer Chemother Pharmacol ; 61(4): 717-20, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17571263

ABSTRACT

Here we report an unusual case of mixed Wilms' tumour and angiosarcoma in a 38-year-old female patient who presented with haematuria and right lower back pain. A computed tomographic (CT) scan confirmed a massive renal tumour associated with extensive retroperitoneal lymph node involvement, bony metastases and a right hip fracture. She was initially managed with palliative nephrectomy, which was followed by rapid postoperative deterioration. Histopathology revealed differentiated adult Wilms' tumour with renal angiosarcoma, whereas the pathology of the para-aortic lymph node and bone metastasis revealed angiosarcoma only. In view of her cachexia and cytopaenia, emergency chemotherapy was initiated using a modified regimen of carboplatin, etoposide and vincristine (CEO) in preference to the more traditional but less well-tolerated VAC (vincristine, actinomycin D, cyclophosphamide). Four cycles of this protocol yielded a dramatic response on re-staging CT scan. This case suggests that highly angiogenic tumours such as angiosarcoma may be effectively palliated using agents usually reserved for refractory Wilms' tumour, and supports the view that adult Wilms' tumour is more sensitive to such agents.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hemangiosarcoma/drug therapy , Kidney Neoplasms/drug therapy , Wilms Tumor/drug therapy , Adult , Antineoplastic Agents/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Combined Modality Therapy , Etoposide/administration & dosage , Fatal Outcome , Female , Hemangiosarcoma/pathology , Hemangiosarcoma/surgery , Humans , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Magnetic Resonance Imaging , Neoplasm Metastasis , Neoplasm Recurrence, Local , Platelet Count , Tomography, X-Ray Computed , Vincristine/administration & dosage , Wilms Tumor/pathology , Wilms Tumor/surgery
20.
Phys Rev Lett ; 99(13): 137205, 2007 Sep 28.
Article in English | MEDLINE | ID: mdl-17930631

ABSTRACT

We cool the fundamental mode of a miniature cantilever by capacitively coupling it to a driven rf resonant circuit. Cooling results from the rf capacitive force, which is phase shifted relative to the cantilever motion. We demonstrate the technique by cooling a 7 kHz cantilever from room temperature to 45 K, obtaining reasonable agreement with a model for the cooling, damping, and frequency shift. Extending the method to higher frequencies in a cryogenic system could enable ground state cooling and may prove simpler than related optical experiments in a low temperature apparatus.

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