Using bevacizumab in the fight against malignant glioma: first results in Asian patients.

OBJECTIVES: To investigate the efficacy and safety profile of bevacizumab in combination with irinotecan in Hong Kong Chinese patients with recurrent malignant glioma and to determine whether their response differed from that reported in other populations. DESIGN: Retrospective study. SETTING: Two private clinics and a public hospital in Hong Kong. PATIENTS: Fourteen individuals who presented with recurrent glioma presenting to the hospital between November 2005 and November 2009. INTERVENTION: Salvage therapy with bevacizumab (10 mg/kg) and irinotecan (125 mg/m(2) [340 mg/m(2) for those taking enzyme-inducing antiepileptic drugs]) on a 14-day schedule. RESULTS: A radiological response was observed in 12 (86%) of the patients, four (33%) of whom had a complete response. The median progression-free survival was 6 (range, 1-15) months; 71% remained progression-free at 6 months. The median overall survival was 18 (range, 9-61) months. The most common adverse events during the bevacizumab and irinotecan treatment period were haematological; five patients had grade 2/3 adverse events. Pulmonary embolism occurred in two patients, one of whom died. Intracranial haemorrhage was not detected in any of the 14 treated patients. CONCLUSIONS: Bevacizumab plus irinotecan was at least as effective at treating Chinese patients with recurrent glioma as previously reported in clinical trials in different patient populations.

Two different first-line 5-fluorouracil regimens with or without oxaliplatin in patients with metastatic colorectal cancer.

BACKGROUND: Oxaliplatin, 5-fluorouracil (5-FU), and leucovorin (LV) are standard first-line treatments for patients with metastatic colorectal cancer (mCRC). The aim of this multicentre, open-label, phase IIIb study was to assess the addition of oxaliplatin to two different 5-FU regimens. PATIENTS AND METHODS: Patients with previously untreated mCRC were randomised to arm A [two-weekly oxaliplatin 85 mg/m(2) + either continuous intravenous infusion (CIV) of 5-FU without LV or two-weekly bolus and CIV 5-FU + LV (LV5FU2)] or arm B (5-FU CIV or LV5FU2 alone). Irinotecan monotherapy was planned on progression. RESULTS: A total of 725 patients were enrolled. After a fixed follow-up of 2 years for each patient, 2-year survival rates were 27.3% and 24.8% in arms A and B, respectively (hazard ratio 0.93; 95% confidence interval 0.78-1.10). The addition of oxaliplatin significantly improved response rates (54.1 versus 29.8%; P < 0.0001) and median progression-free survival (7.9 versus 5.9 months; P < 0.0001). The most common grade 3-4 toxic effects were neutropenia (arm A, 33%; arm B, 5%), diarrhoea (arm A, 14%; arm B, 8%), and fatigue (arm A, 9%; arm B, 8%). CONCLUSIONS: Despite improved rates of tumour control, these results failed to demonstrate a survival benefit from the addition of oxaliplatin to infused 5-FU and lend further support to the use of sequential monotherapy in some patients with mCRC.

Efficacy of combination chemotherapy with irinotecan (CPT-11) plus capecitabine in patients with metastatic or advanced colorectal carcinoma--a dual-centre phase II study: the MAC-6.

AIMS: A phase II trial was initiated to evaluate the efficacy and toxicity of combination chemotherapy with irinotecan (CPT-11) plus capecitabine in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Patients received a combination of CPT-11 plus capecitabine. CPT-11 was infused intravenously on day 1 every 2 weeks and oral capecitabine was taken twice daily for 5 days every 7 days. Efficacy and toxicities were assessed. RESULTS: Between 2004 and 2005, 43 patients were enrolled. The overall response rate was 51.35%. With a median follow-up of 13 months, the median time to progression was 10 months (95% confidence interval 7.6-12.3 months); the median survival was 15 months (95% confidence interval 13.9-16.9 months). The most common grade 3 haematological and non-haematological toxicities were neutropenia (5.4%), diarrhoea (8.1%) and hand-foot syndrome (2.7%). CONCLUSIONS: CPT-11 plus capecitabine with a 14 day cycle showed a comparable response with international phase II data with a 3 weekly regimen and was well tolerated as a first-line palliative chemotherapy in patients with metastatic colorectal cancer. The data should be interpreted with caution due to the limited sample size and should be further confirmed by a phase III randomised trial.

Hypersensitivity reactions to oxaliplatin: experience in a single institute.

BACKGROUND: A rising incidence of hypersensitivity reactions to oxaliplatin has been observed as a result of increasing clinical use. Epidemiological and clinical features of these reactions are reviewed. PATIENTS AND METHODS: Records of patients treated with a modified FOLFOX regimen from March 1999 to March 2004 were reviewed. RESULTS: One hundred and eighty patients were identified. Twenty-seven patients (15%) have been labelled as allergic to oxaliplatin, the proportion being higher among those receiving oxaliplatin in palliative second-line or above settings (19.6%) than in adjuvant or palliative first-line settings (10.2%). Some 2.2% of them developed grade 3-4 reactions. The reactions occurred after a mean (+/-SD) of 8.5 (+/-4.2) cycles (range 1-18). Among the 14 patients re-exposed to oxaliplatin, four (28.6%) developed hypersensitivity reaction, in two of whom (14.3%) reactions were grade 3-4 in severity. CONCLUSIONS: The risk of developing hypersensitivity reactions in patients receiving oxaliplatin should not be underestimated. The risk of developing potentially life-threatening hypersensitivity reactions should be explained to patients in the context of the potential benefits of such therapy. Patients receiving oxaliplatin infusion should be closely monitored. Once a patient develops hypersensitivity reaction to oxaliplatin, re-exposure should only be considered if the reaction is mild and there has been documented clinical benefit from previous doses of this agent.

Radiation recall with oxaliplatin: report of a case and a review of the literature.

Oxaliplatin is a new platinum derivative that has significant activity in patients with metastatic colorectal carcinoma. Some of these patients may have been previously treated with radiotherapy. The interaction of radiotherapy with oxaliplatin needs to be further studied. We report a patient with advanced colonic carcinoma who was treated with concomitant chemoirradiation with oxaliplatin and developed a peculiar dermnatitis in the irradiated field after being exposed to subsequent chemotherapy with oxaliplatin.

Apparent cyclophosphamide (cytoxan) embryopathy: a distinct phenotype?

Cyclophosphamide (CP) is an alkylating agent widely used in treating cancer and autoimmune disease. CP is classified as a pregnancy risk factor D drug and is teratogenic in animals, but population studies have not conclusively demonstrated teratogenicity in humans. Six isolated reports of prenatally exposed infants with various congenital anomalies exist, but to date no specific phenotype has been delineated. The purpose of this report is to document a new case of in utero CP exposure with multiple congenital anomalies and to establish an apparent CP embryopathy phenotype. The mother had systemic lupus erythematosus and cyclophosphamide exposure in the first trimester. She also took nifedipine, atenolol, clonidine, prednisone, aspirin, and potassium chloride throughout pregnancy. The infant had growth retardation and multiple anomalies including microbrachycephaly, coronal craniosynostosis, hypotelorism, shallow orbits, proptosis, blepharophimosis, small, abnormal ears, unilateral preauricular pit, broad, flat nasal bridge, microstomia, high-arched palate, micrognathia, preaxial upper limb and postaxial lower limb defects consisting of hypoplastic thumbs, and bilateral absence of the 4th and 5th toes. Chromosomes were apparently normal. The reported cases of in utero exposure to cyclosposphamide shared the following manifestations with our patient: growth deficiency, developmental delay, craniosynostosis, blepharophimosis, flat nasal bridge, abnormal ears, and distal limb defects including hypoplastic thumbs and oligodactyly. We conclude that (a) cyclophosphamide is a human teratogen, (b) a distinct phenotype exists, and (c) the safety of CP in pregnancy is in serious question.

Longitudinal study of hepatitis C viremia in chronic hepatitis C.

Serial serum samples from 20 untreated patients with chronic hepatitis C virus (HCV) infection were tested for HCV RNA by a nested polymerase chain reaction assay using primers from the highly conserved 5' noncoding region to determine the relationship between hepatitis C viremia and the activity of liver disease during the natural course of chronic HCV infection. Semiquantitation of serum HCV RNA level was achieved by testing serial 10-fold dilutions of RNA extracts to determine the end-point titer. All the patients were HCV RNA positive at presentation. There was a poor correlation between the initial HCV RNA titer and serum transaminase levels. All patients except one were persistently HCV RNA positive during a follow-up period of 1.5-15 years, although 17 (85%) had periods of normal or near-normal transaminase levels. There was no correlation between changes in the serum transaminase levels and HCV RNA titer. Patients with chronic HCV infection have persistent viremia despite fluctuations in ALT levels.

A prospective study of hepatitis C virus infection among renal transplant recipients.

BACKGROUND: Chronic non-A, non-B hepatitis is a major cause of liver disease in renal transplant recipients. METHODS: One hundred eight-five renal allograft recipients, including 151 who had been prospectively followed up for 24 months, were studied to determine the prevalence and course of hepatitis C virus (HCV) infection. Antibody to HCV (anti-HCV) was measured by enzyme immunoassay, and HCV RNA was measured by nested polymerase chain reaction assay. RESULTS: Twenty-three (12.4%) patients were positive for anti-HCV and/or HCV RNA: 19 (10.3%) were anti-HCV positive; and HCV RNA was detected in 18 (94.7%) anti-HCV-positive and 4 (2.4%) anti-HCV-negative patients. Markers of HCV infection persisted in all HCV-positive patients over the 2-year period. Most HCV-positive patients acquired HCV infection before or at the time of transplantation. The incidence of new infection after transplantation was 0.45% per patient-year. Anti-HCV and/or HCV RNA was detected in 75% of patients with biochemical chronic non-A, non-B hepatitis, but transaminase levels were persistently normal in 30.4% of HCV-positive individuals. CONCLUSIONS: HCV infection is common among renal transplant recipients. Testing for HCV RNA is important because some patients might not produce anti-HCV. Transaminase levels cannot be used as a surrogate marker of HCV infection in these patients.

Prevalence of hepatitis C virus infection in hemodialysis patients: a longitudinal study comparing the results of RNA and antibody assays.

We longitudinally studied 51 patients from two hemodialysis centers to determine the prevalence of hepatitis C virus infection in hemodialysis patients. Serum samples were tested for antibody to HCV by first- and second-generation enzyme immunoassays and for hepatitis C virus RNA by nested polymerase chain reaction assay. Antibody to hepatitis C virus was detected in the initial serum samples by first-generation enzyme immunoassay and second-generation enzyme immunoassay in 6 (11.8%) and 11 (21.6%) patients, respectively. First-generation enzyme immunoassay had a false-positive rate of 33.3% and a false-negative rate of 63.6%. Hepatitis C virus RNA was found in eight second-generation enzyme immunoassay-positive patients (72.7%) and in one patient negative for antibody to hepatitis C virus (2.5%) giving an overall positivity rate of 17.6%. After 19 mo, antibody to hepatitis C virus was detected in 15 patients (29.4%) on second-generation enzyme immunoassay; hepatitis C virus RNA was found in 13 patients (25.5%). Hepatitis C virus markers persisted in all 12 patients with initial evidence of hepatitis C virus infection. Three patients acquired hepatitis C virus infection during the interim, giving a new infection rate of 4.9% per patient-year. Antibody to hepatitis C virus, hepatitis C virus RNA or both was detected in 55.6% of patients with biochemical changes suggestive of non-A, non-B hepatitis. Of the 15 antibody to hepatitis C virus, second-generation enzyme immunoassay-positive patients, 66.7% had persistently normal serum transaminase levels. In summary, hepatitis C virus infection is common among hemodialysis patients. First-generation enzyme immunoassay is an unreliable assay for antibody to hepatitis C virus in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Seroepidemiological survey of hepatitis E in Hong Kong by recombinant-based enzyme immunoassays.

The agent that causes the enterally transmitted form of non-A, non-B hepatitis has been cloned and called hepatitis E virus (HEV). We have carried out a seroepidemiological survey on the prevalence of hepatitis E in Hong Kong. In a retrospective study, serum from 394 patients with acute viral hepatitis and 355 healthy subjects was tested for antibodies to HEV (anti-HEV) with a recombinant-based enzyme immunoassay. 65 (16.5%) patients with hepatitis were positive for IgM anti-HEV and 23 (5.8%) were also positive for IgM anti-HEV. Of 18 patients diagnosed as having acute non-A, non-B, non-C hepatitis, 6 were IgM anti-HEV positive. 17 (6%) patients in whom acute hepatitis A was diagnosed were also infected with HEV. None of 70 patients with acute hepatitis B or C or exacerbation of chronic hepatitis B was IgM anti-HEV positive. 57 (16.1%) of the healthy subjects were positive for IgG anti-HEV. The prevalence of IgG anti-HEV was higher in subjects over 20 years old than in younger subjects (24% vs 4%, p < 0.0001). IgG anti-HEV was detected in 26% of subjects who were positive for IgG antibody to HAV and in 7% of those negative for that antibody (p < 0.0001). We demonstrated the validity of the recombinant-based enzyme immunoassays for the diagnosis of hepatitis E. Our results suggest that hepatitis E accounts for a third of non-A, non-B, non-C hepatitis in Hong Kong and that coinfection of hepatitis A and E can occur.

Isopycnic centrifugation of chromatin in renografin solutions.

Solutions of Renografin (30-60%) can be centrifuged to form density gradients in the range from 1.0 g/cm(3) to 1.4 g/cm(3) or, alternatively, preformed gradients can be made which under appropriate conditions of centrifugation have an indefinite stability. Such solutions have a low viscosity and a relatively low ionic strength. The density of DNA in such solutions is surprisingly low ( approximately 1.14 g/cm(3)). Crude chromatin can be sedimented to an equilibrium position in such gradients, corresponding to a density of 1.2(4) g/cm(3), or slightly lower, depending on the method of preparation. The complex is shown to contain DNA, RNA, protein, and possibly some lipoprotein. Most of the RNA can be removed with RNase without any significant effect on the density of the chromatin.