TACE Combined with PSE in Treating Hepatocelluar Carcinoma with Hypersplenism

OBJECTIVE To observe the effectiveness and safety of transcatheter arterial chemoembolization (TACE) combined with partial splenic embolization (PSE) in treating primary hepatocelluar carcinoma (HCC) with hypersplenism. METHODS Thirty HCC patients with liver cirrhosis, portal hypertension and hypersplenism were treated with TACE and PSE. The degree of tumor volume reduction and remission of hypersplenism were observed. RESULTS The tumor reduction rate of the HCC was 73.3%. Twenty-eight patients had hypersplenic remission with a rate of 93.3%. There were no severe complications such as hepatic abscesses. CONCLOUSION TACE combined with PSE is a safe and effective method to treat HCC with liver cirrhosis, portal hypertension and hypersplenism.     

Radiological Imaging in Patients with Esophageal Carcinoma

Diagnostic imaging is carried out in patients with esophageal carcinoma in order to decide on thetherapeutical procedure,to control therapy,to document complications and to assess concomitant diseases.Chest X-rays and esophagograms give a 2-dimensional view of the X-ray absorption in a-dimensionalexamination volumes,the diagnostic accuracy thus being limited by overshadowing.Because of the robustexamination technique,the broad availability and the low costs chest X-rays are usually used for short-termcontrols under therapy and follow-up.Esophagography is carried out in order to asses the exact locationand length of a known esophageal carcinoma prior to therapy and in order to assess peristaltic disturbancesand fistulas.CT and MRI provide tomographic images with a spatial resolution of up to 1 mm allowingthe reconstruction of high-resolution images not only in the transversal but also in any other plain.Thediagnostic accuracy of esophagography is comparatively high in T1-T3 stages (80%-90%).T1 and T2tumors cannot be diagnosed by CT and MRI,because both methods do not visualize the mucosa (unlikeesophagography and endoscopy) and the esophageal wall layers (unlike EUS).Infiltration depth tends tobe overestimated in T1 and T2 carcinomas and to be underestimated in T3 and T4 cancers.CT andMRI cannot detect metastases in normally sized lymph nodes and cannot accurately differentiate betweenbenign and malignant lymphadenopathy in enlarged nodes with a reported sensitivities and specifities of60% and 74%,respectively.However,further prospective studies using up to date CT and MR technologyare needed to assess the present diagnostic situation.CT and MRI do not only visualize the mediastinum,but also the lungs,the pleura and the skeleton as well as the neck and the abdomen thus providing acomprehensive overview of the TNM stage in 3 body regions.     

Studies with interferon-α in human tumors

Clinical trials with IFN-α, produced from buffy coats of leukocytes, have been going on at Radiumhemmet, Karolinska Hospital since 1969. In some of the benign and malignant tumor diseases studied, IFN has been shown to induce regressions. In the case of the benign tumor juvenile laryngeal papillomatosis, IFN has been shown to be superior to other treatment modalities. So far IFN has not been shown to be superior to conventional treatment in any of the malignant tumors studied.     

A phase I study of Triapine® in combination with doxorubicin in patients with advanced solid tumors

Purpose

To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine^® administered in combination with doxorubicin.

Study design

Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine^® IV on days 1–4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m² and Triapine^® 25 mg/m². PK analysis was performed at various time-points before and after treatment.

Results

Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m², Triapine^® 45 mg/m²), two patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional three patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m²) with Triapine^® 45 mg/m². The two patients enrolled on this level had two DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine^® were reduced to 45 and 25 mg/m², respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer.

Conclusions

Pretreated patients with advanced malignancies can tolerate the combination of Triapine^® and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m² on day 1 and Triapine^® 25 mg/m² on days 1–4 of a 21-day cycle.     

Intravesical chemotherapy with 4′-epi-Adriamycin in patients with superficial bladder tumors

Summary We evaluated the effects of 4-epi-Adriamycin (EPI), a derivative of Adriamycin (ADR), in intravesical instillation chemotherapy. The patients received two courses of three daily instillations of 50–80 mg EPI dissolved in 30 ml physiological saline on 3 consecutive days, with an interval of 4 days between courses. Full evaluation was possible in 33 of 35 patients with superficial bladder tumors treated with EPI. Complete response was observed in 4 cases and partial response in 14 cases, giving a response rate of 55%. Side effects such as pollakiuria and pain on micturition occurred in 9 cases. EPI appears to be an effective agent for intravesical instillation chemotherapy in patients with superficial bladder tumors.     

A phase I trial of imatinib in combination with mFOLFOX6–bevacizumab in patients with advanced colorectal cancer

Purpose

Platelet-derived growth factor receptor (PDGFR) inhibition by reducing tumoral interstitial fluid pressure might increase the efficacy of chemotherapy. Imatinib inhibits PDGFR kinase activity at therapeutically relevant doses. This phase I study aimed to assess the maximal tolerated dose (MTD) of imatinib in combination with mFOLFOX6–bevacizumab in patients with advanced colorectal cancer and to identify pharmacokinetic (PK) interactions and toxicities.

Methods

Eligible patients had measurable disease and adequate organ function. On day-14, patients commenced imatinib daily plus bevacizumab (5 mg/kg/2 weekly). Two weeks later (day 1), patients were also treated with full dose mFOLFOX6–bevacizumab for 12 cycles. Blood samples were taken for PK. DLTs defined in the first 6 weeks. Standard dose escalation of imatinib, with 3 patient cohorts: planned dose levels (DL): DL1; 400 mg, DL2; 600 mg, DL3; 800 mg daily.

Results

Ten patients enrolled. DL1 3 patients, DL2 7 patients. DLTs observed in 3 of 6 patients in DL2: febrile neutropenia (2); Grade 3 infection and Grade 4 neutropenia (1). Neutropenia was most frequent AEs: Grade 3/4 in >60 % of patients overall. In DL2 pts, imatinib clearance was reduced post-chemotherapy (P < 0.05). Oxaliplatin and 5FU PK unchanged by imatinib.

Conclusions

MTD was imatinib 400 mg plus full dose mFOLFOX–bevacizumab. Dose escalation of imatinib limited by neutropenia. Further study is warranted as imatinib can be delivered at levels that inhibit PDGFR.     

Metabolic syndrome is associated with better prognosis in patients with tongue squamous cell carcinoma

Introduction:Metabolic syndrome (MS) is associated with several cancers, but it is not clear whether MS affects the prognosis of tongue squamous cell carcinoma (TSCC). This study aimed to evaluate the ...     

Is intravenous iron supplementation with erythropoiesis-stimulating agents beneficial in cancer patients with anemia?

Chemotherapy-induced anemia is often an important problem for cancer patients, and this complication can be treated with erythropoiesis-stimulating agents (ESAs). This commentary discusses the findings of a study by Bastit et al., in which 396 patients with nonmyeloid malignancies and chemotherapy-induced anemia were treated with darbepoetin alfa with or without intravenous iron. This phase III trial showed that intravenous iron supplementation increases the hematopoietic response rates to ESAs in cancer patients; however, this study provides no information as to whether all cancer patients with anemia should receive intravenous iron as well as treatment with ESAs. Further data are needed to identify those patients who might benefit from intravenous iron supplementation in addition to ESAs, in order to avoid overtreatment of patients who are unlikely to benefit from the additional iron. As both ESAs and intravenous iron have known short-term and long-term risks, identification of reliable predictors of response that can guide these treatments is necessary before this strategy can be implemented into practice.     

Incidence of hand–foot syndrome with capecitabine in combination with chemotherapy as first-line treatment in patients with advanced and/or metastatic gastric cancer suitable for treatment with a fluoropyrimidine-based regimen

Introduction

Hand?Cfoot syndrome (HFS) is a limiting toxicity of capecitabine, which is not life-threatening but could compromise capecitabine efficacy.

Materials and methods

This phase II, multicenter, non-controlled study assessed the safety, particularly grade three HFS incidence, and efficacy of four capecitabine-based chemotherapy regimens [cisplatin/capecitabine (CX), epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/capecitabine (EOX) and docetaxel/cisplatin/capecitabine (DCX)] as first-line treatment for advanced and/or metastatic gastric cancer.

Results

One hundred and eight patients were assigned to one of the four treatment groups, according to investigator??s criteria, and grouped together for both safety and efficacy primary analyses. HFS was reported in 31 patients (19.6?%) and its first presentation occurred at a median of 72?days (range 19?C209?days). Grade 3 HFS developed in 6.3, 5.2, 3.7 and 2.4?%, of patients receiving ECX, DCX, EOX or CX chemotherapy regimen, respectively. Capecitabine dose reduction/discontinuation due to HFS was required in 5.7?% of patients (9/158). The most common (>10?%) grade 3?C4 treatment-related AEs were neutropenia (15.2?%), asthenia (12.0?%) and diarrhoea (11.4?%).

Conclusions

A moderate incidence of HFS was reported in patients treated with capecitabine, which generally presented late and required dose reduction in <1/3 of patients. The results suggest that capecitabine may be useful in combination with standard fluorouracil-based regimens in patients with advanced and/or metastatic gastric cancer with favourable safety profile.     

Phase I study of sorafenib in combination with docetaxel and prednisone in chemo-na?ve patients with metastatic castration-resistant prostate cancer

Purpose

We performed a dose-escalation study to investigate the safety of sorafenib in combination with docetaxel and prednisone in chemo-na?ve patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods

Six patients were included per dose level. Following docetaxel infusion on day 1 (75?mg/m²/q3?weeks), sorafenib was administered at 200?mg BID on days 2?C19 (dose level 1), at 200?mg BID on days 1?C21 (dose level 2), at 400?mg BID on days 2?C19 (dose level 3), at 400?mg BID on days 1?C21 (dose level 4). Maximal tolerated dose (MTD) was exceeded if ??2 patients experienced dose-limiting toxicities (DLT) during cycle 1. The recommended phase 2 dose for sorafenib was defined as one dose level below MTD. If MTD was not reached, the highest feasible dose would be selected to treat an expanded cohort to confirm safety.

Results

Two DLTs were observed during sorafenib dose-escalation consisting of grade 4 febrile neutropenia (dose level 2) and grade 3 hand-foot syndrome (HFS) (dose level 3). Our pharmacokinetic results showed an increased exposure to docetaxel across all dose levels during sorafenib comedication. The main grade ??3 toxicities were neutropenia (35?%), HFS (27?%), and febrile neutropenia (19?%). The prostate-specific antigen (PSA) response rate was 74?%. Median overall survival was 25.2?months.

Conclusion

Three-weekly docetaxel and prednisone could be combined with sorafenib at 400?mg BID on days 1?C21 without reaching MTD. However, we observed a pharmacokinetic interaction between sorafenib and docetaxel, associated with significant toxicities, raising concerns about the safety of this combination in mCRPC.     

Was the drop in mammography rates in 2005 associated with the drop in hormone therapy use?

BACKGROUND:

In 2005, mammography rates in the United States dropped nationally for the first time among age‐eligible women. An increased risk of breast cancer related to hormone therapy (HT) use reported in 2002 led to a dramatic drop in its use by 2005. Because current users of HT also tend to have higher mammography rates, the authors examined whether concurrent drops in HT and mammography use were associated.

METHODS:

Multivariate logistic regression was used to test for an interaction between HT use and survey year, controlling for a range of measurable factors in data from the 2000 and 2005 National Health Interview Surveys (NHIS).

RESULTS:

Women ages 50 to 64 years were more likely to report a recent mammogram if they also reported more education, a usual source of care, private health insurance, any race except non‐Hispanic Asian, talking with an obstetrician/gynecologist or other physician in the past 12 months, or were currently taking HT. Women aged ≥65 years were more likely to report a recent mammogram if they also reported younger age (ages 65‐74 years), more education, a usual source of care, having Medicare Part B or other supplemental Medicare insurance, excellent health, any race except non‐Hispanic Asian, talking with an obstetrician/gynecologist or other physician in the past 12 months, or were currently taking HT.

CONCLUSIONS:

The change in HT use was associated with the drop in mammography use for women ages 50 to 64 years but not for women aged ≥65 years. NHIS data explained 70% to 80% of the change in mammography use. Cancer 2011;. © 2011 American Cancer Society.     

Endoscopic options in children： experience with 134 procedures

OBJECT： There are frequent applications for endoscopy in neurosurgery. However, endoscopic surgery in children has peculiar characteristics and is associated with different rates of success. In this study, the authors report on their experience with 134 consecutive endoscopy procedures performed in 126 patients〈18 years of age. METHODS： Between April 1993 and October 2007, 134 endoscopic procedures were performed in 126 children. Indications for surgery included brain tumors in 48 children, cystic lesions in 24, aqueductal stenosis in 23, various malformations in 20, hemorrhage and infarction in 6, and isolated ventricles in 5 children. In this long-term followup study, data were analyzed with respect to clinical and radiological success rates, as well as shunt dependence both in relation to lesion origin, and to the type of endoscopic procedure performed （endoscopic third ventrieulostomy [ETV], septostomy, aqueductoplasty, or cystocistemostomy）. Finally, the influence of patient age on the success rate was evaluated.