A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is an important regulator of the chronic inflammation contributing to tumour progression. Infliximab, an anti-TNF-alpha monoclonal antibody was investigated in this trial of patients with advanced cancer. The primary objectives were to determine the safety profile and biological response of infliximab in a cancer population. Clinical response was a secondary objective. PATIENTS AND METHODS: Forty-one patients received infliximab at 5 mg/kg (n = 21) or 10 mg/kg (n = 20) i.v. at 0 and 2 weeks and then every 4 weeks. Post-treatment samples were measured for changes in plasma and serum TNF-alpha, CCL2, IL-6 and C-reactive protein (CRP). RESULTS: Infliximab was well tolerated with no dose-limiting toxic effects. At both doses of infliximab, neutralisation of serum TNF-alpha was observed after 1 h while plasma CCL2, IL-6 and serum CRP were decreased 24 and 48 h following infliximab administration. Seven patients experienced disease stablisation (range 10-50+ weeks). There was no evidence of disease acceleration in any patient. CONCLUSIONS: Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-alpha and CCL2 being correlated with infliximab response.     

A double-blinded, randomized, placebo-controlled trial of infliximab in subjects with active pulmonary sarcoidosis

STUDY OBJECTIVES: To evaluate the safety and tolerability of infliximab in the treatment of active pulmonary sarcoidosis, and to provide an initial assessment of the efficacy of infliximab in the treatment of active pulmonary sarcoidosis. DESIGN: Double-blind, randomized, placebo-controlled phase II study. SETTING: Multicenter. PATIENTS: Active Radiographic Stage II, III, and IV active pulmonary sarcoidosis despite corticosteroids or previous intolerance to corticosteroids. INTERVENTION: Infliximab 5mg/kg (group I) or placebo (group II) at weeks 0 and 2 and open-label infliximab 5mg/kg for all subjects at weeks 6 and 14. MEASUREMENTS: Pulmonary function, chest radiographs, dyspnea stage, SF-36. RESULTS: Mean vital capacity (VC) at wk 0 was 2.47 +/- 0.2 (group I) and 2.37 +/- 0.31 (group II). At 6 weeks the mean +/- SD relative change in VC compared to baseline was 15.22 +/- 9.91% for group I (n=13) and 8.39 +/- 3.33% for group II (n=6) (p=0.65). Four patients had serious adverse events, including decreased WBC and elevated CPK (1 patient), pneumonia (1 patient), cellulitis, acute renal failure, pulmonary embolus and death (1 patient), and visual field defect (1 patient). CONCLUSIONS: Infliximab may improve VC in patients with active PS resistant to steroids. Larger scale, longer term studies will be needed to assess both safety and efficacy.     

Infliximab for the treatment of severe steroid refractory acute graft-versus-host disease in three patients after allogeneic hematopoietic transplantation

Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic peripheral blood stem cell transplantation (PBSCT). Patients with severe aGVHD not responding to treatment with steroids have a poor prognosis. We treated three patients with severe aGVHD refractory to steroids with infliximab. Patients (MDS 1, NHL 1, ALL 1) developed grade II-IV GVHD at a median of 13 days (range 9-17) after non-myeloablative PBSCT (HLA mismatched). All patients had received treatment with high-dose steroids for a median of 7 days (range 7-10) in addition to mycophenolate mofetil (MMF) (one). Infliximab was given in 3 weekly doses of 5 mg/kg. In one of three patients a partial resolution of diarrhea and minor improvement of skin were observed. One patient died with refractory GVHD. Infliximab is apparently an effective drug for the treatment of aGVHD, but can be more effective at doses of 5 mg/kg or higher and/or by administering it repeatedly every week.     

Leflunomide for chronic sarcoidosis

BACKGROUND AND AIM: Leflunomide (Arava) is a cytotoxic drug which has been used as a single agent or in combination with methotrexate for the treatment of rheumatoid arthritis. It appears to have less toxicity than methotrexate. The use of leflunomide for sarcoidosis patients has not been systematically evaluated. METHODS: The records were reviewed from all patients treated at a tertiary sarcoidosis center from July 2002-July 2003, and information from patients treated with either leflunomide or methotrexate was analyzed for efficacy and toxicity. RESULTS: Thirty-two patients were treated with leflunomide; fifteen patients received concurrent therapy with methotrexate. The most common indications for therapy were ocular and lung disease. Complete or partial response to leflunomide was seen in 12 of 17 treated with leflunomide alone, and 13 of 15 treated with leflunomide plus methotrexate. There was no difference in the response rate for eye [23/28 (82%)] versus pulmonary disease [12/16 (75%)]. Seventeen patients were treated with leflunomide alone because of methotrexate toxicity (nausea in 12 and pulmonary symptoms in five). All but two tolerated leflunomide. Three patients experienced nausea leading to drug discontinuation, but no other serious adverse reaction was encountered with leflunomide. CONCLUSION: Leflunomide was well tolerated in patients with chronic sarcoidosis. It appears to be as effective as methotrexate, with less toxicity. It should be considered as an alternative in chronic sarcoidosis patients who cannot tolerate methotrexate.     

Real World Outcomes and Hepatotoxicity of Infliximab in the Treatment of Steroid-Refractory Immune-Related Adverse Events

Background and aims: Current guidelines state that infliximab is contraindicated for the treatment of immune checkpoint inhibitor-related hepatitis (ir-hepatitis) due to the risk of inducing further liver damage. As this recommendation is largely based on the use of infliximab for rheumatologic diseases, we evaluated the efficacy and hepatotoxicity of infliximab in patients with steroid-refractory immune-related adverse events (irAEs). Methods: We retrospectively reviewed consecutive patients treated with infliximab for irAEs at Princess Margaret Cancer Centre. To assess hepatotoxicity, we compared the mean value of ALT, AST, and total bilirubin (BT) before and after infliximab treatment. We used logistic regression to assess factors associated with infliximab efficacy. Results: Between January 2010 and February 2019, 56 patients were identified. The median age of the patients was 63 (27–84) years. Colitis was the most frequent toxicity (66%), followed by pneumonitis (11%). Infliximab was used to treat ir-hepatitis in one patient. The median number of infliximab doses was 1 (1–3) and led to toxicity resolution in 43 (76%) patients. The mean ALT, AST, and BT levels before and after infliximab treatment were not statistically different. The patient treated for ir-hepatitis had a complete recovery, with no incremental liver toxicity. Conclusions: In this dose-limited setting, infliximab was effective in resolving irAEs and did not induce hepatotoxicity.     

Comparison of etoposide and cisplatin with bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide for salvage treatment in small cell lung cancer. A Southwest Oncology Group Study

Small cell lung cancer patients who failed primary systemic therapy or who failed after response were randomly assigned to salvage treatment with etoposide (VP-16) and cisplatin (CDDP) or bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide (BTOC). Good risk patients were those who had tolerated prior chemotherapy well, those who had not had prior radiation therapy, and those who were 65 years of age or younger. Patients with a history of poor tolerance, prior radiation therapy, or those who were older than 65 years of age were classified as poor risk. Forty-five patients were randomized to the BTOC regimen and 58 to the VP-16/CDDP regimen. The overall remission rate was 13% (13 of 103 patients). Good risk patients treated with the BTOC regimen had a remission rate of 27% (three of 11 patients), which was the same rate as patients treated with the VP-16/CDDP regimen (three of 11 patients). Poor risk patients had remission rates of 9% (three of 34 patients) with the BTOC regimen and 9% (four of 47 patients) with the VP-16/CDDP regimen. The median survival time from the start of therapy was 16 weeks for all patients. BTOC good risk patients had a median survival time of 10 weeks, as compared with 14 weeks for poor risk patients. VP-16/CDDP good risk patients had a median survival time of 35 weeks, as compared with 12 weeks for poor risk patients. Although based on small numbers, the advantage in survival time for good risk patients treated with VP-16/CDDP over those treated with BTOC is statistically significant. Prior exposure to VP-16 did not influence the outcome of patients treated with VP-16/CDDP. Both regimens produced moderate toxicity, but were generally well tolerated. It was concluded that VP-16/CDDP may be a useful salvage treatment for good risk patients, despite its limited remission rate. Also, it was found that BTOC has no value for patients in this setting and that neither regimen helps patients who are poor risk.     

Improvement of small fiber neuropathy in a sarcoidosis patient after treatment with infliximab

We describe a patient with severe small fiber neuropathy (SFN) accompanied by autonomic involvement, who was experimentally treated with infliximab, an anti-tumour necrosis factor-alpha (TNF-alpha) therapy. Six months after this treatment was started his symptoms completely resolved. Until now they did not return. Repeated temperature threshold testing (TTT) as well as cardiovascular autonomic function test clearly improved after one year therapy. This case reveals two important issues. First, it shows that SFN seems not an irreversible disorder, even in severe cases. Second, TNF-alpha may be a crucial cytokine in the pathogenesis of SFN in sarcoidosis and eventually also in other immune mediated inflammatory diseases.     

Myalgia and Arthralgia Immune-related Adverse Events (irAEs) in Patients With Genitourinary Malignancies Treated With Immune Checkpoint Inhibitors

BackgroundMyalgia and arthralgia immune-related adverse events (irAEs) in patients treated with checkpoint inhibitors (CPIs) present a clinical challenge. We describe the clinical characteristics and treatment of myalgia and arthralgia irAEs in CPI-treated patients with genitourinary (GU) malignancies.Patients and MethodsPatients with GU malignancies who were treated with CPIs and developed myalgia and arthralgia irAEs that resulted in interruption or discontinuation of CPI therapy were reviewed. Patient-, disease-, and irAE-related data were collected and analyzed.ResultsTwenty-one patients were identified. Eighteen (86%) had renal cell carcinoma; 3 (14%) had urothelial carcinoma. The majority (71%) were male; the median age at diagnosis was 56 years (range, 36-78 years). CPI therapy included anti-programmed death-ligand 1 (29%), anti-programmed cell death protein 1 (48%), and combined programmed cell death protein 1/cytotoxic T-lymphocyte-associated protein 4 antibodies (24%). The median time from CPI initiation to myalgia and arthralgia irAE was 5.1 months (range, 0.23-50.5 months). All patients were treated with prednisone with a median initial dose of 40 mg/d (range, 10-90 mg/d) for a median duration of 64 weeks (range, 3-242 weeks). Treatment with methotrexate (14%), infliximab (14%), tocilizumab (10%), gabapentin (10%), and etanercept (5%) was also required in some patients. Six (29%) patients restarted CPI therapy following symptom improvement, 3 (15%) switched to a subsequent therapy, and 12 (55%) patients had an ongoing sustained response to therapy (median, 14.5 months; range, 3-55 months) despite no subsequent anti-cancer therapy.ConclusionMyalgia and arthralgia irAEs in CPI-treated patients with GU malignancies vary in timing of presentation, severity, and treatment. Multidisciplinary teams that include a rheumatologist are critical for optimal management. Durable response to CPIs can be maintained even after therapy discontinuation.     

Experience with interferon in chronic hepatitis B in Egypt

Forty patients with compensated chronic active hepatitis B and elevated aminotransferases who were HBsAg and HBeAg positive were randomised to a treatment group receiving recombinant interferon alpha-2b (rIFN alpha-2b) or no treatment as a control group. The treated patients were divided into 2 groups, group I (n = 12) received IFN in a dose of 5 MU/m2 thrice weekly by subcutaneous injection for 16 weeks, and group II (n = 8) received the same dose daily for the same duration. Patients were followed up for 12 months after therapy ended. Initiation of IFN therapy was associated with an increase in aminotransferases, reaching a peak at 4-6 weeks in most patients, associated with clearance of HBeAg. At end of follow-up, 81% of the treated patients had cleared HBeAg vs 33% of the control group (p less than 0.01). Changes in other HBV markers were more frequent in the treated patients, though insignificantly. The type of response to therapy was significantly related to the duration of illness, being shortest in those who cleared HBsAg. A complete response to therapy with loss of HBsAg was associated with marked reduction in biochemical and histological activity. A partial response with clearance of HBeAg was associated with moderate improvement in biochemical parameters and ongoing activity in liver histology; whereas persistence of HBeAg was associated with elevated aminotransferases and histological deterioration in most cases. The rise in aminotransferases during seroconversion was associated with hepatic decompensation and death on 3 occasions: one during spontaneous seroconversion, and the other 2 during IFN therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combination treatment of oral terbinafine with topical terbinafine and 10% urea ointment in hyperkeratotic type tinea pedis

Hyperkeratotic‐type tinea pedis is chronic and recalcitrant to topical antifungal agents. Some topical antifungal agents are effective; however, long duration of therapy is required, which often reduce the treatment compliance of patients. To seek for short period therapy of hyperkeratotic type tinea pedis, in this study, we observed the efficacy and safety of treatment of topical terbinafine and 10% urea ointment combined oral terbinafine. Participants with hyperkeratotic type tinea pedis were randomly assigned to two groups. Patients in group I were treated with oral terbinafine for 2 weeks and topical terbinafine and 10% urea ointment for 4 weeks, whereas in group II, only the above topical agents were applied for 12 weeks. Clinical improvement rates and fungal eradication rates were compared between the two groups at 24 weeks after the initiation of treatment. The group I had stopped the topical therapy 8 weeks earlier than group II. There were no significant differences in mycological eradication rates and clinical improvement rates between the two groups, besides, no major side effects were noted in both groups. The short combination therapy with oral terbinafine was effective and safe; it should be a valuable option for patients with hyperkeratotic type tinea pedis.     

CD4+CD28-T cells are expanded in sarcoidosis

BACKGROUND AND AIM: A subset of CD4+ lymphocytes lacking CD28, an important costimulatory molecule, is increased in certain inflammatory conditions. However, studies have not directly studied CD4+CD28-lymphocytes in patients with chronic sarcoidosis. The aim of this study was to further characterize the CD4+CD28-T cell population in patients with sarcoidosis, particularly those with active disease. METHODS: Seventeen patients with chronic sarcoidosis and 15 blood donors were studied. Bronchoalveolar lavage cells were available for paired analysis in seven sarcoid patients. In 4 sarcoid patients, adequate sample was available for intracellular cytokine analysis by flow cytometry. IFN-gamma production in plasma and BAL was determined by ELISA and cytometric bead array analysis and compared to previously studied controls. RESULTS: Peripheral blood from patients with sarcoidosis had a significantly higher proportion of CD4+CD28- cells compared with healthy donors. A higher percentage of CD4+CD28- cells was evident in the BAL relative to peripheral blood in patients with active sarcoid. IFN-gamma levels were greater both in the plasma and concentrated BAL fluid of sarcoid subjects compared to controls. The majority of IFN-gamma and TNF-alpha producing lymphocytes were CD28+ in both healthy blood donors and sarcoid subjects. CONCLUSIONS: CD4+CD28- cells are increased in the peripheral blood and lungs of patients with sarcoidosis requiring treatment. These cells may contribute to the inflammatory response; however, they are not major contributors of IFN-gamma or TNF-alpha.     

Adverse long-term effect of corticosteroid therapy in recent-onset sarcoidosis

BACKGROUND AND AIM: The indications for corticosteroid therapy (CST) in persons with pulmonary (stages II-IV) sarcoidosis lacking compelling symptoms are undefined. Some studies have demonstrated a long-term adverse outcome in treated individuals in comparison with controls. The objectives of this analysis are: 1) to seek corroborative evidence for an adverse long-term effect of CST in pulmonary sarcoidosis; 2) to determine which individuals are at risk; and 3) to provide evidence-based guides for CST in pulmonary sarcoidosis. METHOD: I summarized and stratified according to disease duration all CST trials of pulmonary sarcoidosis providing long-term follow-up, published in the English language, identified in the MEDLINE database, 1966-2001, employing the search term "sarcoidosis AND therapy trials," and in a review of bibliographies of retrieved articles. RESULTS: Three competent concurrent controlled CST trials and two non-concurrent controlled trials in young persons with recently diagnosed stage II-III sarcoidosis showed that, long-term, those allocated for treatment were more than twice as likely as untreated subjects to exhibit radiographic or clinical progression or death. In controlled trials in patients with disease of intermediate duration, the effect of universal vs. selective provision of CST varied from neutral to slightly beneficial. Patients with progressive chronic sarcoidosis either improved or stabilized, intermediate term, in response to CST. CONCLUSIONS: CST in persons with recent onset sarcoidosis is more likely to result in long-term harm than benefit; in persons with sarcoidosis of intermediate duration, its effect is close to neutral; persons with progressive chronic pulmonary sarcoidosis respond favorably intermediate-term.     

Methotrexate is steroid sparing in acute sarcoidosis: results of a double blind, randomized trial

BACKGROUND AND AIM OF THE WORK: Methotrexate has been steroid sparing for some patients with chronic sarcoidosis. We wished to determine whether methotrexate can be steroid sparing in the first year of corticosteroid therapy in sarcoidosis. METHODS: Patients with new onset, symptomatic disease within four weeks of starting on prednisone were randomized to receive either methotrexate or placebo for the next year. They were seen monthly and prednisone dosage was tapered following a pre-determined schedule. RESULTS: Of 24 patients enrolled, only 15 received at least six months of therapy. Since methotrexate appears to take six months to be effective, only patients who completed six or more months of therapy were evaluated. The amount of prednisone per day decreased for both groups: methotrexate (First 6 months: Median 26 (Range 15-37) mg/day); Second 6 months 8 (1-22) mg/day, p < 0.01) and placebo (First 6 Months 28 (24-33) mg/day; Second 6 months 16 (11-22) mg/day, p < 0.02), with less prednisone used for the methotrexate patients versus placebo in the last six months (p < 0.01). There was also less weight gain for those patients receiving methotrexate. There was no difference in toxicity between methotrexate and placebo. The difference between methotrexate versus placebo was not seen when all patients (including the dropouts) were analyzed. CONCLUSIONS: Methotrexate can be a steroid sparing agent in acute sarcoidosis.     

Use of fluticasone in acute symptomatic pulmonary sarcoidosis

BACKGROUND: Inhaled corticosteroids have been used with variable success in sarcoidosis. The role of the inhaled corticosteroid fluticasone in symptomatic pulmonary patients was studied. METHODS: Twenty-two patients at five institutions who had been given an initial dose of oral corticosteroids within the prior four weeks were enrolled in a randomized double blind trial of inhaled fluticasone. An algorithm for the dosage of prednisone including rules for reducing dose was developed and applied at all centers. RESULTS: Of the 21 patients seen for more than one visit, 10 received fluticasone and 11 placebo. There was no significant difference in the improvement of vital capacity or average daily dose of prednisone for the fluticasone versus placebo. Eight of ten patients taking fluticasone had improvement in cough, while only 6 of 11 patients on placebo had improved cough despite taking oral corticosteroids (p = 0.36, N.S.). The algorithm for decreasing corticosteroid dosage was exactly applied in over 80% of patient visits and oral corticosteroids were used throughout most of the year of treatment. Patients registered higher complaints regarding increased appetite and polyuria when on ten mg or more prednisone a day. There was no clinical difference in the rate of toxicity for the fluticasone versus placebo group. CONCLUSION: A standard approach to tapering oral corticosteroids was followed in over 80% of patient visits. Oral corticosteroids were associated with significant complaints, while inhaled corticosteroids were well tolerated.     

中药青黛治疗慢性出血性放射性直肠炎

Objective:To evaluate the efficacy and safety of Qing Dai (indigo naturalis).a traditional Chinese medicine,in the treatmenl for chronic hemorrhagic radiation proctitis.Methods:Ten patients with chronic hemorrhagic radiation proctitis between January 2005 to January 2008 were Veated with Qing Dai.Qing Dai was administered orally at a dose of 1.5 g,bid for 5 consecutive days,every 2 weeks for two courses.Patients were followed up every 3 months.The clinical response and side-effects were evaluated.Results:Six patients showed improvement of rectal bleeding to grade 0-1 arer 1 course of Qing Dai therapy.Four patients had reduced rectal bleeding to grade 0-1 after 2 courses of the therapy.The median follow-up time was 10 months frange:6-24).During the follow-up period,1 patient experienced recurrent rectal bleeding and was managed with topical formalin dabbing.which controlled the symptom.No treatment toxidty was observed.Conclusion:Qing Dai may be a safe and effective treatment for chtonic hemorrhagic radiation proctitis.     

Phase II trial of toremifene in androgen-independent prostate cancer: a Penn cancer clinical trials group trial

Toremifene has antiestrogenic and estrogenic properties in vitro and in vivo. In addition, it may have antiangiogenesis and antimicrotubule properties at higher doses. Studies have demonstrated the efficacy of this agent in the treatment of metastatic breast cancer. We performed a phase II trial of toremifene in patients with androgen-independent prostate cancer (AIPC). Patients with an increasing prostate-specific antigen level despite castrate testosterone levels and antiandrogen withdrawal were eligible. Patients could not have received prior salvage hormonal therapy or chemotherapy. Patients received toremifene at 300 mg/m2/d orally (maximum dose 640 mg/d). Fifteen patients were treated. Patients received treatment for a median of 13 weeks (range, 4-30 weeks). The median age was 72 years (range, 58-80 years). The median Eastern Cooperative Oncology Group performance status was 0. The treatment was well tolerated and toxicity was mild. Two patients had grade III hepatic toxicity; one had grade III hyperglycemia. There were no treatment-related deaths. No objective responses were demonstrated. In summary, toremifene is not effective therapy for AIPC at the dose and schedule evaluated in this trial.     

Quality of life in patients with gastroenteropancreatic tumors treated with [177Lu-DOTA0,Tyr3]octreotate.

PURPOSE: To evaluate the quality of life (QoL) in patients with metastatic somatostatin receptor positive gastroenteropancreatic tumors treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate) therapy. PATIENTS AND METHODS: Fifty patients who had been treated with 600 to 800 mCi of (177)Lu-octreotate and had a follow-up of at least 3 months were studied. The patients completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 before therapy and at follow-up visit 6 weeks after the last cycle. Overall QoL and specific QoL domains of both the total group of patients and subgroups according to treatment outcome were analyzed. Twenty-four patients had regression, 19 had stable disease, six had progressive disease, and one had nonassessable disease status. Analysis of variance was used for statistical comparison. RESULTS: A significant improvement in the global health status/QoL scale was observed after therapy with (177)Lu-octreotate (P <.01). The score increased significantly six weeks after therapy to a mean of 78.2, up from 69.0 (scale range, 0 to 100). Furthermore, significant improvement was observed in the role, emotional, and social function scales. The symptom scores for fatigue, insomnia, and pain were significantly decreased. Patients with proven tumor regression most frequently had an improvement of QoL domains. Unexpectedly, patients with progressive disease also indicated an improvement in their global health/QoL score. CONCLUSION: (177)Lu-octreotate therapy significantly improved the global health/QoL and several function and symptom scales in patients with metastasized gastroenteropancreatic tumors, but especially in those patients with proven tumor regression.     

Clinical trial of recombinant leukocyte A interferon as initial therapy for favorable histology non-Hodgkin's lymphomas and chronic lymphocytic leukemia. An Eastern Cooperative Oncology Group pilot study

Twenty patients with disseminated favorable histology non-Hodgkin's lymphomas (16 patients) or chronic lymphocytic leukemia (four patients) who had not received previous chemotherapy were treated with recombinant leukocyte A interferon (IFL-rA) (Hoffmann-La Roche, Nutley, NJ). Treatment was administered in a moderate dose (12 X 10(6) U/m2) by intramuscular (IM) injection three times weekly for 8 weeks, followed by weekly maintenance therapy for an additional 16 weeks in patients responding to therapy. Five patients with stable disease at 8 weeks received four additional weeks of three-times-weekly treatment at an escalated dose (25 X 10(6) U/m2). Interferon was tolerated without severe toxicity by most patients, although treatment was discontinued prematurely due to side effects in four patients. Objective tumor responses (one complete response [CR] and six partial responses [PRs]) were seen in seven of 16 patients with lymphoma (44%). One of four patients with chronic lymphocytic leukemia also experienced a PR. Median time-to-progression from initiation of therapy among responding patients was 26 + weeks (range, 7 + to 84 + weeks). This study has demonstrated single agent antitumor activity of IFL-rA given in a tolerable outpatient dosage regimen in patients with advanced favorable histology non-Hodgkin's lymphomas, and serves as a basis for further trials of IFL-rA combined with chemotherapy as initial therapy for such patients in the future.     

Pulmonary hypertension in sarcoidosis

BACKGROUND: Pulmonary hypertension has been notreported in some patients with sarcoidosis. METHODS: We retrospectively studied 53 sarcoidosis patients with persistent dyspnea despite systemic therapy for their sarcoidosis. All patients underwent cardiac catheterization to determine pulmonary artery (PA) pressure. RESULTS: Of the 53 patients, six were found to have left ventricle (LV) dysfunction, including four cases of diastolic dysfunction. Of the remaining 47 patients, 26 had a systolic PA pressure > or = 40 Torr and 25 had a mean PA pressure > or = 25 Torr. Using univariate analysis of those patients with normal LV function, echocardiography, vital capacity, and diffusion lung of carbon monoxide (D(L)co) correlated with systolic and/or mean pulmonary artery pressure. For the PA systolic, only the echocardiographic estimated PA pressure and D(L)CO % predicted remained in the multiple regression model (Coefficient of determination = 0.76, p < 0.005 for both). For the PA mean pressure, the only independent variable was the echocardiographic estimate of the PA pressure (Coefficient of determination = 0.70, p < 0.005). While echocardiography was useful in many cases, in nine cases PA pressure could not be estimated because there was no tricuspid regurgitation seen. Seven of these patients had a measured PA pressure of > or = 40 Torr. Seven patients with moderate to severe pulmonary hypertension were treated with pulmonary vasodilator therapy. Five patients experienced good clinical response. CONCLUSION: Pulmonary hypertension was commonly found in sarcoidosis patients with persistent dyspnea. For some of these patients, treatment of the pulmonary hypertension was associated with improved clinical status.     

Phase II study of weekly albumin-bound paclitaxel for patients with metastatic breast cancer heavily pretreated with taxanes

PURPOSE: Nanoparticle albumin-bound paclitaxel, a solvent-free, albumin-bound paclitaxel, demonstrated antitumor activity in patients with taxane-naive metastatic breast cancer (MBC). We examined albumin-bound paclitaxel (100 mg/m2 or 125 mg/m2 administered weekly) to determine the antitumor activity in patients with MBC whose disease progressed despite conventional taxane therapy. PATIENTS AND METHODS: Women with MBC that was previously treated with taxanes were eligible for participation. Taxane failure was defined as metastatic disease progression during taxane therapy or relapse within 12 months of adjuvant taxane therapy. Primary objectives were response rates (RRs) and the safety/tolerability of albumin-bound paclitaxel. RESULTS: Women were treated with albumin-bound paclitaxel 100 mg/m2 (n = 106) or 125 mg/m2 (n = 75) on days 1, 8, and 15 of a 28-day cycle. Response rates were 14% and 16% for the 100-mg/m2 and 125-mg/m2 cohorts, respectively; an additional 12% and 21% of patients, respectively, had stable disease (SD) > or = 16 weeks. Median progression-free survival times were 3 months at 100 mg/m2 and 3.5 months at 125 mg/m2; median survival times were 9.2 months and 9.1 months, respectively. Survival was similar for responding patients and those with SD. No severe hypersensitivity reactions were reported. Patients who developed treatment-limiting peripheral neuropathy typically could be restarted on a reduced dose of albumin-bound paclitaxel after a 1-2-week delay. Grade 4 neutropenia occurred in < 5% of patients. CONCLUSION: Albumin-bound paclitaxel 100 mg/m2 given weekly demonstrated the same antitumor activity as albumin-bound paclitaxel 125 mg/m2 weekly and a more favorable safety profile in patients with MBC that had progressed with previous taxane therapy. Survival of patients with SD > or = 16 weeks was similar to that of responders.