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.     

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.     

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.     

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.     

β-Glucuronidase levels in patients with fibrocystic breast disease

Certain enzymes in tissues and body fluids may, through reversal of the detoxification process, influence the composition and availability of steroid hormones, toxins, and carcinogens. The ubiquitous enzyme -glucuronidase, which hydrolyzes glucuronide conjugates, thereby reversing one of the main detoxification and excretion pathways, was found to vary in concentration in different cysts over a 300-fold range. The distribution was a continuum, devoid of discrete sub-populations. Evidence obtained on selected cyst fluids of high and low -glucuronidase activities indicated that the level of the enzyme significantly influenced the ratio of unconjugated: glucuronidated estradiol. The patients with fibrocystic breast disease fell into 2 distinct subpopulations on the basis of their serum -glucuronidase activity. In one group the activity was near normal, while in the second group the average serum -glucuronidase activity was 3-fold higher than in the women who did not have benign breast disease.     

Leiomyomatosis peritonealis disseminata in association with Currarino syndrome?

Background  

Leiomyomatosis peritonealis disseminata (LPD) is a rare disease in which multiple smooth muscle or smooth muscle-like nodules develop subperitoneally in any part of the abdominal cavity. No reports of multiple congenital malformations associated with LPD have been found in the English literature.     

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.     

Metronomic Chemotherapy in Patients with Advanced Non—Small-Cell Lung Cancer Associated with Long-Term Survival

PurposeMetronomic chemotherapy is defined as lower-dose, more frequent chemotherapy treatments. Herein, we report 14 consecutive patients with advanced non—small-cell lung cancer (NSCLC; 3 patients with stage IIIB disease, 11 patients with stage IV disease) who were treated between 2002 and current time with continuous weekly chemotherapy until disease progression or 1–2 cycles (12–24 weeks) beyond optimal response.Patients and MethodsPatients with disease progression were treated with a salvage weekly chemotherapy regimen until progression. Since 2005, patients who had optimal response were placed on maintenance erlotinib. All patients had Eastern Cooperative Oncology Group performance status of 0–1, initiated first-line treatment at our clinic, and received ≥ 12 weeks of planned chemotherapy.ResultsAll patients had a partial or complete response as their best response during the course of treatment. Median survival of this group of patients was > 30 months. One patient (patient 14) with bronchoalveolar lung cancer had a partial response (PR) in her lungs but developed brain metastasis that progressed soon after whole-brain radiation therapy. She was then placed on erlotinib and survived for 13 months. Another patient (patient 13) died of possible stroke while still in PR. Overall side effects from treatments were mild, with the most common side effects being grade 1/2 fatigue (75%) and peripheral neuropathy (40%), but no grade 3 or 4 neuropathy was observed.ConclusionMetronomic chemotherapy might be associated with long-term survival in patients with advanced NSCLC. Further clinical trials to confirm these findings are warranted.