Right- and left-subclavian vein port-a-cath systems: comparison of complications.

BACKGROUND: Central venous access systems are frequently used for delivery of medications; however, few studies have compared surgical and postoperative complications of right versus left access via the subclavian vein (SCV). The aim of this study was to compare the surgical and postoperative complications associated with Port-A-Cath system insertion via the right and left SCV. METHODS: The medical records of patients who received Port-A-Cath insertion via the SCV for parenteral chemotherapy between August 2004 and July 2008 were reviewed. The incidence of surgical and postoperative complications was compared between patients who received right- versus left-SCV Port-A-Cath insertion. RESULTS: A total of 1,848 patients were included in the study. Right-SCV catheterization was attempted in 1,029 (55.7%) patients and was successful in 866 (84.2%). Left-SCV catheterization was attempted in 819 (44.3%) patients and was successful in 651 (79.5%). The mean length of postoperative follow-up was 417.3 ± 401.3 and 396.7 ± 379.9 days for the right- and left-SCV groups, respectively. The incidence of SCV puncture failure was significantly lower in the right-SCV group (12.3%) compared with the left-SCV group (16.8%, p = 0.006). The incidence of catheter knotting at the ipsilateral brachiocephalic vein was also significantly lower in the right-SCV group (0.0%) compared with the left-SCV group (0.5%, p = 0.038), as was the incidence of catheter occlusion (1.0% for right SCV vs. 3.5% for left SCV, p = 0.001). CONCLUSION: These findings suggest that the right-SCV approach is superior to the left-SCV approach for Port-A-Cath insertion.

Upregulation of tumor necrosis factor-alpha gene by Epstein-Barr virus and activation of macrophages in Epstein-Barr virus-infected T cells in the pathogenesis of hemophagocytic syndrome.

A potentially fatal hemophagocytic syndrome has been noted in patients with malignant lymphomas, particularly in EBV-infected T cell lymphoma. Cytokines, such as interferon-gamma (IFN-gamma), TNF-alpha, and IL-1alpha, are elevated in patients' sera. To verify whether infection of T cells by EBV will upregulate specific cytokine genes and subsequently activate macrophages leading to hemophagocytic syndrome, we studied the transcripts of TNF-alpha, IFN-gamma, and IL-1alpha in EBV-infected and EBV-negative lymphoma tissues. By reverse transcription PCR analysis, transcripts of TNF-alpha were detected in 8 (57%) of 14 EBV-infected T cell lymphomas, higher than that detected in EBV-negative T cell lymphoma (one of six, 17%), EBV-positive B cell lymphoma (two of five, 40%) and EBV-negative B cell lymphomas (one of seven, 14%). Transcripts of IFN-gamma were consistently detected in T cell lymphoma and occasionally in B cell lymphoma, but were independent of EBV status. IL-1alpha expression was not detectable in any category. Consistent with these in vivo observations, in vitro EBV infection of T cell lymphoma lines caused upregulation of TNF-alpha gene, and increased secretion of TNF-alpha, but not IFN-gamma or IL-1alpha. Expression of TNF-alpha, IFN-gamma, and IL-1alpha was not changed by EBV infection of B cell lymphoma lines. To identify the specific cytokine(s) responsible for macrophage activation, culture supernatants from EBV-infected T cells were cocultured with a monocytic cell line U937 for 24 h. Enhanced phagocytosis and secretion of TNF-alpha, IFN-gamma, and IL-1alpha by U937 cells were observed, and could be inhibited to a large extent by anti-TNF-alpha (70%), less effectively by anti-IFN-gamma (31%), but almost completely by the combination of anti-TNF-alpha and anti-IFN-gamma (85%). Taken together, the in vivo and in vitro observations suggest that infection of T cells by EBV selectively upregulates the TNF-alpha expression which, in combination with IFN-gamma and probably other cytokines, can activate macrophages. This study not only highlights a probable pathogenesis for virus-associated hemophagocytic syndrome, but also suggests that anti-TNF-alpha will have therapeutic potential in the context of their fatal syndrome.

Induction therapy of newly diagnosed acute nonlymphocytic leukemia with idarubicin and cytosine arabinoside--the Taiwan experience.

From October 1993 to December 1994, 26 patients with newly diagnosed and untreated acute nonlymphocytic leukemia (ANLL) received induction chemotherapy with the 3 + 7 regimen, i.e., idarubicin (IDA) 12 mg/m2/d for 3 days any cytosine arabinoside (Ara-C) 100 mg/m2/d for 7 days. Complete remission (CR) was achieved in 80.8% of the whole group and in 66.7% (two of three) of the elderly subgroup (age > or = 60 years). Seventeen patients achieved a CR after only one course, whereas four needed two courses. Toxicity was tolerable. All of the patients experienced myelosuppression, and infection episodes were noted in all except one patients. Other toxicities included vomiting (62%, mostly mild to moderate, grade I/II), diarrhea (46%, mostly grade I), mucositis (65%, mostly grade I), and alopecia (100%). None presented with liver dysfunction or cardiotoxicity. Of the 21 complete responders, one refused further consolidation, 20 received either two additional courses of IDA/Ara-C or high-dose Ara-C as consolidation, and one died of infectious complications during consolidation. As of May 1995, nine had relapsed, and 11 (55%) continued in CR for 6 to 21 months (median, 14.5). All four patients who needed two courses of IDA/ Ara-C to achieve remission had relapsed, with either high-dose Ara-C or allogeneic bone marrow transplantation (BMT) as postremission therapy. We suggest that induction failure with one course of IDA/Ara-C is a poor prognostic factor in ANLL.

Relation of left atrial spontaneous echo contrast with prethrombotic state in atrial fibrillation associated with systemic hypertension, idiopathic dilated cardiomyopathy, or no identifiable cause (lone).

To investigate the association of left atrial (LA) spontaneous echo contrast with the hemostatic state in nonrheumatic atrial fibrillation (AF), we examined the plasma levels of prothrombin fragment 1+2 and fibrinopeptide A in 73 patients with chronic nonrheumatic AF undergoing transesophageal echocardiography and 38 age-matched normal subjects. The results support the theory that LA spontaneous echo contrast in nonrheumatic AF is associated with a hypercoagulable state, especially in patients with marked LA spontaneous echo contrast.

In-vitro effects of antineoplastic prostaglandins on human leukemic cell growth and normal myelopoiesis.

The effects of prostaglandin (PG)E1, PGD2 and 9-deoxy-delta 9-PGD2 (PGJ2) on the clonogenic growth of six kinds of human leukemic cell lines (K562, KG1, HL60, U937, THP1 and Molt4) and normal human myeloid progenitor cells (CFU-GM) were studied using semisolid agar cultures. While the degree of suppression of leukemic growth by PGE1 varied from cell line to cell line, PGD2 and PGJ2 equally suppressed the growth of all leukemic cell lines. The potency of growth inhibition was as follows: PGJ2 greater than PGD2 greater than PGE1. The increase of cellular cAMP level induced by prostaglandin treatment did not parallel their cytotoxic potency. Normal myeloid colony formation was also suppressed by PGE1, PGD2 or PGJ2. In contrast to the preferential inhibition of macrophage colony formation by PGE1, such lineage-selective suppression was not observed for PGD2 or PGJ2. These findings suggest that PGD2 and PGJ2 potently inhibit the leukemic growth by a different mechanism from that of PGE1 and by a cAMP-independent mechanism. These prostaglandins seem to be promising chemotherapeutic agents for acute leukemia.

Epstein-Barr virus-containing T-cell lymphoma and atherosclerotic abdominal aortic aneurysm in a young adult.

Malignant lymphoma infiltrating the abdominal aorta and resulting in an aortic aneurysm has never been documented. We report here a case of angiocentric T-cell lymphoma in a 33-year-old man who for months presented intermittent fever, splenomegaly, and an abdominal pulsatile mass. Angiography revealed extensive aneurysmal dilatation of the infrarenal abdominal aorta, bilateral iliac artery, and right common femoral artery. Splenic abscess and infected abdominal aortic aneurysm were initially suspected. An urgent splenectomy and aneurysmectomy with an aortic bifemoral bypass were performed. Pathological examination of the aortic aneurysm showed extensive necrosis, severe atherosclerosis, and lymphoma cell infiltration of the aortic wall. The lymphoid cells in the aorta and spleen were stained positive for CD45RO, CD56, and CD8, but negative for CD4 and CD19. Double-labeling immunohistochemistry and in situ hybridization using EBER1 for Epstein-Barr virus (EBV) revealed positive nuclear staining in the atypical T-lymphoid cells. This is the first definitive proof of peripheral T-cell lymphoma involving the abdominal aorta. Our evidence also supports that the EBV infection of T cells could be responsible for the atherosclerosis and hypertriglyceridemia, and the angiocentricity of the tumor cells apparently results in the presenting atherosclerotic aortic wall destruction, providing an additional causative concept for abdominal aortic aneurysm.

Rapid engraftment of mast cells of donor origin in a case of acute myeloid leukemia with mast cell leukemia after allogeneic stem cell transplantation.

Mastocytosis is a rare disease characterized by an abnormal increase of mast cells in tissues. We report a case of acute myeloid leukemia (AML) with t(8;21) and mast cell leukemia (MCL) in which the mastocytosis persisted after standard chemotherapy and allogeneic stem cell transplantation, although the myeloid leukemia achieved molecular complete remission soon after induction chemotherapy. Donor-type mast cells were noted on d31 after transplant. No c-kit mutation was found before or after the transplant. This represents the first reported case in which rapid engraftment of mast cells of donor origin was documented. Thus, the possibility that the mast cell originates from a common myeloid precursor cell may be questioned and a reactive process should be considered in some cases of systemic mastocytosis.

Cytoprotective effect of reduced glutathione in hydrogen peroxide-induced endothelial cell injury.

The kinetic effects of hydrogen peroxide (H2O2) on cultured endothelial cells isolated from bovine carotid artery were studied. The cytoprotective effects of glutathione (GSH) on H2O2-induced cell injury were also investigated. H2O2-induced a dose- and time-dependent cell injury in cultured endothelial cells. H2O2-induced cell injury was blocked by simultaneous treatment by catalase, but not by superoxide dismutase. H2O2 also induced endogenous PGI2 biosynthesis, and the maximum PGI2 production was reached after 1 h treatment. Stimulation of PGI2 production was parallel with arachidonate release from H2O2-treated cells. However the prostaglandin biosynthesis enzyme activity in cells was inhibited by H2O2 treatment. When the cells were treated with GSH, the intracellular GSH reached a plateau after 3 h treatment. Both H2O2-induced cell injury and PGI2 production were significantly inhibited by the 3 h pretreatment with GSH. The cytoprotective effect of GSH was completely inhibited by buthionine sulfoximine which is a specific inhibitor of gamma-glutamylcysteine synthetase. The results indicate that the cytoprotective effect of GSH on H2O2-induced cell injury in cultured bovine carotid artery endothelial cells depends on the increase in intracellular GSH content.

The effect of recombinant human erythropoietin on hemostatic status in chronic uremic patients.

The hemostatic effects of recombinant human erythropoietin (rHuEP) were investigated in 20 patients with end-stage renal disease (thirteen on hemodialysis, seven without dialysis) receiving this hormone. We studied their hemograms and coagulation profiles before and at 1 month after initiation of rHuEP therapy. One month after rHuEP administration, improvement in anemia (16/20, 80%) and shortening of bleeding time (17/19, 89.5%) were observed. Shortening or correction of bleeding time was achieved in three patients without any increase of the hemoglobin level. This means that factors other than the increased hematocrit level might contribute to shortening bleeding time in uremic patients receiving rHuEP treatment. The platelet count, prothrombin time, partial thromboplastin time, and fibrinogen level did not change over the course of rHuEP therapy. Thrombosis of vascular access was not observed, and heparin doses were not increased in this short-term period. A significant decrease was found in the plasminogen level, from 108.5% to 88.2% (p less than 0.05), in uremic patients on hemodialysis. The antithrombin III level also decreased, from 98.8% to 89.8% (p less than 0.05), and its level dropped to below normal ranges in six of thirteen patients (46%) on hemodialysis after treatment with rHuEP. No significant change was noted in the levels of antithrombin III, plasminogen, and alpha 2-antiplasmin in uremic patients not receiving dialysis. These results suggest that rHuEP administration induces increased extracorporeal dialyzer clotting and consumption coagulopathy, and that this extracorporeal consumption coagulopathy may play a role in the genesis of thrombotic complications.

Selective IgA deficiency with recurrent vasculitis of the central nervous system.

We describe an unusual case of selective IgA deficiency complicated by recurrent vasculitis of the central nervous system (CNS). The patient suffered from two episodes of CNS vasculitis, one of which was located in the cerebrum and the other in the cerebellum. The vasculitic process resulted in brain tumor-like lesions shown by computed tomography. There was no evidence of associated connective tissue diseases. Vasculitis in other organs or tissues was not noted. This is the first detailed description in the English literature of pathologically proven CNS vasculitis in a patient with selective IgA deficiency. Our report demonstrates that isolated CNS angiitis can be a rare clinical feature of selective IgA deficiency.

Treatment of classical type Kaposi's sarcoma with paclitaxel.

Paclitaxel has recently been shown to be effective in treating acquired immunodeficiency syndrome-associated Kaposi's sarcoma. We report good therapeutic effects of paclitaxel in two patients with classical form Kaposi's sarcoma (KS) which had poor or partial response to chemotherapy (vincristine, vinblastine, oncovin, bleomycin, epirubicin, dactinomycin, decarbazine) and interferon alpha-2b. Paclitaxel appears to be active against Kaposi's sarcoma as a single agent. The experience suggests that paclitaxel is an effective alternative in the treatment of classical form Kaposi's sarcoma.

Bone marrow metastasis in nasopharyngeal cancer: early detection using EBER1 in situ hybridization.

BACKGROUND: Previous studies have reported the abundant expression of EBER1 in primary nasopharyngeal carcinoma (NPC) metastatic to lymph nodes and bone marrow (BM). This study was done to research the use of EBER1 in situ hybridization to detect micrometastasis in the marrow of NPC patients. PATIENTS AND METHODS: A total of 41 patients who underwent BM biopsy either for routine pretherapeutic evaluation or suspected bone marrow metastasis were enrolled for study. Thirty-two patients underwent BM biopsy for routine staging examination (Group I) and 10 were examined for unexplained cytopenia, leukoerythroblastosis, disseminated intravascular coagulation, or extensive bone metastasis (Group II). The authors applied EBER1 in situ hybridization to investigate the expression of EBER1 in 42 BM specimens. Examinations were performed on paraffin embedded tissues using polymerase chain reaction-derived, digoxigenin-labeled EBER1 DNA probes. RESULTS: Eight of 42 specimens (19%) were positive for BM metastasis. Just one (3%) had bone marrow involvement in Group I. However, seven (70%) were positive in Group II. All but one of them with bone marrow metastasis showed positive EBER1 in situ hybridization in the BM. Another patient suspected of having BM metastasis was negative for cytokeratin, but was positive for EBER1 in situ hybridization. CONCLUSION: Routine bone marrow study is not recommended in the staging of NPC, since only 3% of patients had BM metastasis. EBER1 in situ hybridization of marrow specimens cannot detect malignant cells earlier in NPC, but can be usefully applied to cases of equivocal marrow metastasis.

Papillary cystic tumors of the pancreas: assessment of malignant potential by analysis of progesterone receptor, flow cytometry, and ras oncogene mutation.

BACKGROUND: Although the biologic behavior of papillary cystic tumor (PCT) of the pancreas is more favorable than the adenocarcinoma, a malignant form has been reported. There has been much controversy as to the histologic evidence for malignancy. The purpose of this study is to evaluate whether the ras oncogene mutation is present in the PCT, together with hormone receptor status and DNA flow cytometry that can be used to predict tumor aggressiveness. MATERIALS AND METHODS: In 6 collected cases of PCT, estrogen receptors (ER) and progesterone receptors (PR) were detected by immunohistochemical techniques, DNA ploidy and S-phase fraction (SPF) were studied by flow cytometry, and H, K, and N-ras oncogene mutation were analyzed by polymerase chain reaction (PCR). RESULTS: General strong positive immunostaining of PR and negative staining of ER are found in all 6 cases of PCT, including 5 adolescent girls and one 55-year-old women with areas of anaplastic transformation. Flow cytometry analysis revealed diploid DNA in all 6 cases but higher SPF in the anaplastic portion of the old one. None of the 6 cases showed H-, K-, or N-ras oncogene mutation. CONCLUSIONS: These results suggest PR status and ras oncogene mutation appear to be not useful in predicting aggressive behavior. DNA ploidy and S-phase fraction may provide useful information for prognosis, but their more precise prognostic value of PCT needs a larger number of cases to clarify.

Bcl-2 and proliferating cell nuclear antigen (PCNA) expression correlates with subsequent local recurrence in nasopharyngeal carcinomas.

Many anticancer treatments, including radiation therapy, have been demonstrated to work through apoptosis. The treatment of choice on nasopharyngeal carcinoma (NPC), a radiosensitive tumor, is radiotherapy. Apoptosis therefore provides a good model to predict or re-evaluate the therapeutic response in NPC. Cellular genes such as p53 and bcl-2 have been shown to be involved in apoptosis. Proliferating cell nuclear antigen (PCNA) is a useful marker for proliferating cells. This study was designed to investigate whether the expression of p53, bcl-2 and PCNA, evaluated on tumor specimens obtained at diagnosis, is indicative of the subsequent local recurrence and distant metastasis following radiation therapy. We analyzed the expression of p53, bcl-2 and PCNA by immunohistochemical methods from NPC specimens prior to radiation therapy. A total of 63 T3/T4 NPC patients including 10 patients with local relapse (Group I), 19 patients with distant metastasis (Group II), and 34 disease-free patients (Group III) were assessed. Six of the 10 (60%) group I NPC, 4 of the 19 (21.1%) group II NPC, and 13 of the 34 (38.2%) group III NPC exhibited positive p53 expression. For bcl-2 immunostaining, 8 of the 10 (80%) group I NPC, 10 of the 19 (52.6%) group II NPC, and 10 of the 34 (29.4%) group III NPC were positive. High PCNA labelling index was shown in 6 of the 10 (60%) group I NPC, 7 of the 19 (36.8%) group II NPC, and 5 of the 34 (14.7%) group III NPC. The bcl-2 and PCNA reactivity in NPC developing local recurrence after radiation therapy was significantly higher than that in the disease-free NPC (p < 0.05). These findings show that the overexpression of bcl-2 and high PCNA labelling index are probably related to local relapse in NPC patients receiving radiation therapy alone as primary treatment.

Eradiction of H. pylori results in regression of B-cell low grade gastric MALToma with evident B-symptoms.

Although it is well known that eradication of H. pylori may result in either complete or partial regression of low-grade B-cell mucosa-associated lymphoid tissue lymphoma (MALToma), it would be of clinical interest to determine whether the B-symptoms of patients with MALToma could be relieved by eradication of H. pylori. Here, we report on a 29 year-old female case with B-cell low-grade gastric MALToma with apparent B-symptoms. Her peripheral blood also disclosed large granular lymphocytes (LGL). The B-symptoms of this patient were quickly relieved within 2 weeks after starting an anti-H. pylori regimen; peripheral blood LGLs were clearly decreased as well. Complete regression of MALToma was determined 4 months after the anti-H. pylori regimen. Thereafter, the patient has been disease-free and in good general condition during a 2-year follow-up.

Leukemia cutis in acute lymphocytic leukemia masquerading as viral exanthem.

Leukemia cutis is a specific skin lesion caused by infiltration of leukemic cells into the skin. It is uncommon in acute lymphocytic leukemia (ALL). It typically manifests as red or violaceous papules, nodules, or plaques, mainly on the face. Leukemia cutis presenting with a generalized viral exanthem-like maculopapular eruption appears to be rare in the English literature. We report such a case. A 19 year-old man presented with a generalized purpuric maculopapular eruption of eight day's duration. Hematologic studies showed changes of acute lymphocytic leukemia, T-cell type. A skin biopsy specimen revealed a cuff-like, dense, perivascular infiltration of atypical lymphocytes in the upper and mid-dermis, consistent with leukemia cutis. The rash resolved in two weeks after chemotherapy. Our case illustrates that leukemia cutis should be considered in the differential diagnosis of a generalized morbilliform viral exanthem-like eruptions. Skin biopsy is important in establishing the diagnosis.

Sweet's syndrome in a severely neutropenic patient during therapy with recombinant human granulocyte colony-stimulating factor.

We report a new case of Sweet's syndrome (SS) associated with recombinant human granulocyte colony-stimulating factor (rHuG-CSF) therapy in a patient with acute myelogenous leukemia (AML). The patient developed a fever in association with multiple tender, purpuric and pustular skin lesions and swelling of both calves after receiving rHuG-CSF 3 micrograms/kg/d for 4 days. The absolute neutrophil count was 0.55 x 10(9)/L at onset. A skin biopsy revealed a dense neutrophilic infiltration in the dermis without evidence of vasculitis or infection. All skin and calf lesions regressed within 1 week after prednisolone therapy. Physicians should be aware of potential neutrophil-mediated dermatoses in patients with severe neutropenia on rHuG-CSF treatment.

Clinical characteristics of and response to combination chemotherapy and subsequent application of international prognostic index in non-Hodgkin's lymphoma--an experience from a medical center in Southern Taiwan.

A retrospective analysis was performed of 117 non-Hodgkin's lymphoma (NHL) patients (72 male and 45 female, mean age 55 years) treated at NCKUH between July 1988 and December 1993. Of the 115 patients who could be classified by Ann Arbor staging system, 26 patients (22.2%) were in stage 1; 23 (19.7%) in stage 2; 29 (24.8%) in stage 3; and 37 (31.6%) in stage 4. According to the International Working Formulation, three patients (2.6%) were low grade NHL, 90 (76.9%) were intermediate, and 8 (6.8%) were high grade NHL. Histologically, diffuse large cell NHL accounted for 52.1% of cases, followed by 16.2% of cases exhibiting diffuse mixed NHL. Immunophenotype analysis was available in 95 cases, which revealed 76 (80%) cases exhibiting B-cell origin, 17 (18%) cases exhibiting diffuse mixed NHL. Immunophenotype analysis was available in 95 cases, which revealed 76 (80%) cases exhibiting B-cell origin, 17 (18%) cases exhibiting T-cell origin and 2 (2%) cases were of null cell type. All patients underwent two groups of induction chemotherapy, either CHOP (Cyclophosphamide, Epirubicin, Oncovin, and Prednisolone), or "modified" COPBLAM (Cyclophosphamide, Epirubicin, Oncovin, and Prednisolone), or "modified" COPBLAM (Cyclophosphamide, Epirubicin, Oncovin, Vinblastine, Bleomycin, Procarbazine, and Prednisolone). Seventy-two cases treated through COPBLAM and 45 cases treated through CHOP were evaluated. The response rate (RR) to COPBLAM treatment was 72.2% and was 68.9% for the CHOP group (P = 0.51). The 5-year overall survival rate (OAS) was 44.1% for COPBLAM, versus 40% for CHOP (P = 0.15). The disease-free survival (DFS) was 72.6% at 63 months for COPBLAM and 58% at 51 months for CHOP (P = 0.16). Neither B cell nor T-cell lineages of NHL showed any statistical difference in RR (P = 0.53, DFS (P = 0.58) or OAS (P = 0.97) to the different treatments. Using multiple logistic analysis, two independent factors, high LDH and advanced stage, were found to adversely affect the rate of complete remission. The application of the International Prognostic Index to our patients needs modification, which suggests the necessity of more evaluation before it can accurately be applied to all international series of NHL.

Comparison of oral controlled-release morphine with transdermal fentanyl in terminal cancer pain.

BACKGROUND: Controlled-release morphine (MST) given twice daily provides a simpler and more convenient treatment regimen than 4-hourly opioid administration for the control of cancer pain. Recently, a new formulation of transdermal fentanyl (TDF) has been developed which provides a new route for the treatment of cancer pain. The present study was designed to compare the analgesic efficacy, safety and adverse effects of MST and TDF in the management of chronic cancer pain. METHODS: In this open, comparative and randomized study, patients were treated with oral morphine hydrochloride immediate-release (MHIR) in the stabilization phase and then the prescription was switched to MST or TDF for 14 days in the treatment phase. Oral MHIR was provided as rescue medication for breakthrough pain. Assessments of the pain intensity, pain frequency, degree of pain improvement, profile of mood states, quality of sleep, activity status and adverse effects were performed before and after the stabilization phase and before and after the treatment phase. RESULTS: Forty of 47 cancer patients completed the study with 20 patients in each group. There were significant (p < 0.05) improvements in pain intensity, pain frequency, mood states and quality of sleep in both groups before and after treatment, while improvement in the activity status was not significant. No specific adverse effects were encountered except for drowsiness which occurred in 6 patients treated with MST and 5 treated with TDF (p < 0.05). Insomnia was significantly improved (p < 0.05) with both regimens compared with that in the period before treatment. There were no significant differences between the two study groups in analgesic efficacy or adverse effects. CONCLUSIONS: These results suggest that TDF and MSt are safe and effective analgesics for the management of chronic cancer pain. However, TDF provides a simpler and more convenient treatment for those patients with severe nausea, vomiting or dysphagia.

A phase II study of erlotinib in combination with bevacizumab versus chemotherapy plus bevacizumab in the first-line treatment of advanced non-squamous non-small cell lung cancer.

BACKGROUND: Molecularly targeted agents for non-small cell lung cancer (NSCLC) can provide similar efficacy to chemotherapy without chemotherapy-associated toxicities. Combining two agents with different modes of action could further increase the efficacy of these therapies. The TASK study evaluated the efficacy and safety of the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with the anti-angiogenic agent bevacizumab as first-line therapy in unselected, advanced non-squamous NSCLC patients. METHODS: Patients were recruited from December 2007 to September 2008. Planned sample size was 200 patients, a total of 124 patients were randomized. Patients were randomized using a minimization algorithm 1:1 to receive bevacizumab (iv 15 mg/kg day 1 of each 21-day cycle) plus chemotherapy (gemcitabine/cisplatin or carboplatin/paclitaxel standard doses, 4-6 cycles) (BC arm) or bevacizumab plus erlotinib (p.o. 150 mg/day; BE arm) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). If the hazard ratio (HR) of PFS for BE relative to BC was above 1.25 at the pre-planned interim analysis in favor of BC, the study would be re-evaluated. Secondary endpoints included overall survival, response rate and safety. RESULTS: All randomized patients (n = 63 BE; n = 61 BC) were evaluated for the efficacy analyses. At the updated interim analysis, median PFS was 18.4 weeks (95% confidence interval [CI] 17.0-25.1) versus 25.0 weeks (95% CI 20.6-[not reached]) for BE versus BC, respectively (HR for death or disease progression, BE relative to BC, 2.05, p = 0.0183). The incidence of death was 19% for BE treatment compared with 11.5% for BC treatment. The HR for PFS at the updated interim analysis was above 1.25, therefore patients on the BE arm were permitted to change arms or switch to another drug and the study was terminated. Adverse events reported were as expected. CONCLUSIONS: The TASK study did not show a benefit in terms of PFS for the combination of erlotinib with bevacizumab in unselected first-line advanced non-squamous NSCLC compared with chemotherapy plus bevacizumab.