Phase II trial of thalidomide for therapy of radioiodine-unresponsive and rapidly progressive thyroid carcinomas.

BACKGROUND: There are no known effective therapies for distantly metastatic, rapidly progressive thyroid carcinomas unresponsive to radioiodine. Objective: Since thyroid carcinomas are hypervascular and thalidomide is antiangiogenic, we assessed thalidomide's tumoristatic effects and toxicity in a phase II trial. DESIGN: Thirty-six patients with follicular, papillary, insular, or medullary thyroid carcinomas and distant, radioiodine-unresponsive metastases (volumes increasing >or= 30% per year before entry) were accrued between July 2001 and December 2002. Daily thalidomide started at 200 mg, increasing over 6 weeks to 800 mg or maximum tolerated dose. Toxicities and responses were assessed at 8-week intervals with tumor volume assessments. MAIN OUTCOMES: Twenty-eight of 36 patients were evaluable, 5 with partial responses (PR: 18%; 95% confidence interval [95% CI]: 6-37%) and 9 patients with stable disease (SD: 32%; 95% CI: 12-42%) for overall 50% response (95% CI: 31-69%). Median PR duration was 4 months (range: 2-6 months), and SD duration was 6 months (range: 2-14 months). Median survival was 23.5 months for responders (PR + SD) and 11 months for nonresponders. Most frequent toxicity was fatigue (69% grade 1-2, 8% grade 3-4). Four patients had grade 3-4 infections (without neutropenia), one had pericardial effusion, and one had pulmonary embolus. CONCLUSIONS: Thalidomide confers therapeutic benefit in subsets of thyroid cancer patients with rapidly progressive, distantly metastatic disease.     

Thalidomide-based multidisciplinary treatment for patients with advanced hepatocellular carcinoma: a retrospective analysis

AIM: To evaluate the efficacy of thalidomide in combination with other therapies to treat patients with advanced hepatocellular carcinoma (HCC).METHODS: We performed a retrospective analysis of all patients with HCC who were treated with thalidomide for at least two months. The medical records of patients with HCC who were treated at our institution between April 2003 and March 2008 were reviewed. Image studies performed before and after treatment, tumor response, overall survival, and the decrease in α-fetoprotein (AFP) levels were evaluated.RESULTS: A total of 53 patients with HCC received either 100 or 200 mg/d of thalidomide. The patient population consisted of 9 women and 44 men with a median age of 61 years. Thirty patients (56.6%) were classified as Child-Pugh A, and 12 patients (22.6%) were classified as Child-Pugh B. Twenty-six patients had portal vein thrombosis (49.1%), and 25 patients had extrahepatic metastasis (47.1%). The median duration of thalidomide treatment was 6.0 mo. Six of the 53 patients achieved a confirmed response (11.3%), one achieved a complete response (1.9%) and 5 achieved a partial response (9.4%). The disease control rate (CR + PR + SD) was 28.3% (95% CI: 17.8-42.4), and the median overall survival rate was 10.5 mo. The 1- and 2-year survival rates were 45% and 20%, respectively. Only one complete response patient showed an improved overall survival rate of 66.8 mo. Sixteen patients (30.2%) showed more than a 50% decrease in their serum AFP levels from baseline, indicating a better response rate (31.3%), disease control rate (43.8%), and overall survival time (20.7 mo). The therapy was well tolerated, and no significant toxicities were observed.CONCLUSION: Thalidomide was found to be safe for advanced HCC patients, demonstrating anti-tumor activity including response, survival, and AFP decreases of greater than 50% from baseline.     

Thalidomide in advanced hepatocellular carcinoma as antiangiogenic treatment approach: a phase I/II trial

BACKGROUND: The high vascularity of hepatocellular carcinoma (HCC) seems to be a potential therapeutic target. We evaluated the efficacy, toxicity, and histologic response to thalidomide in advanced HCC in a single center phase I/II pilot trial. METHODS: Between September 2000 and August 2004 patients with HCC uneligible for any established therapy were enrolled in the study. The initial thalidomide dosage of 100 mg/day was escalated in 100 mg steps weekly up to 300 mg/day based on tolerability. Discontinuation and dose reduction were based on toxicity. Tumor biopsies were scheduled to assess tumor microvessel density and serum levels of angiogenic factors, vascular endothelial growth factor, basic fibroblast growth factor, and endostatin were determined. RESULTS: Twenty-eight patients with histologically proven HCC were entered into this study. The median maximum-tolerated dose of thalidomide was 300 mg/day. Most common toxicities were fatigue (75%), dizziness (64%), nausea (43%), and constipation (39%). Two patients had stable disease for 2.6 and 5.4 months, the remaining 26 patients had disease progression. The median overall survival was 5.1 months. Well preserved liver function was associated with longer overall survival on univariate analysis (P=0.0279). The serum concentrations of vascular endothelial growth factor and endostatin increased significantly (P=0.039 and P=0.024, respectively) after 3 months of thalidomide treatment. No clear differences were observed between the serum basic fibroblast growth factor concentrations at study entry and after 3 months (P=0.983). Microvessel density did not decrease significantly during thalidomide therapy (P=0.109). CONCLUSION: Thalidomide is moderately tolerated and minimally effective in large HCC.     

Preoperative chemoradiotherapy in cancer of the thoracic esophagus

Surgery with or without adjuvant radiotherapy (RT) is the standard treatment of esophageal cancer. Preoperative radio- and chemotherapy (CT) have been introduced to improve prognosis. We report a phase II prospective non-randomized trial of preoperative RT (42 Gy/25) plus CT (cisplatin 20 mg/mq/day plus 5-fluorouracil 600 mg/mq/day, 1-5 weeks) for the treatment of thoracic esophageal cancer. From 1993, 50 patients were enrolled (40 men and 10 women, mean age 57 years, range 30-75 years). Squamous cell carcinoma accounted for 90% of cases; 10% were adenocarcinoma. Downstaging of the disease was obtained in 77.3% of cases; there were 13 (29.5%) complete responses (CR) and 21 (47.7%) partial responses (PR). Median survival was 28 and 25 months, respectively, for CR and partial response (PR) plus stable disease (SD) and progressive disease (PD) (P = 0.05). Progressive-free median survival was 22 and 17 months, respectively, for CR and PR + SD + PD (P = 0.08). Multimodal treatment of esophageal cancer showed promising results, although not significant, in terms of survival and disease progression for patients achieving a complete pathologic response.     

Association between ADAMTS13 activity–VWF antigen imbalance and the therapeutic effect of HAIC in patients with hepatocellular carcinoma

BACKGROUNDPrediction of HAIC treatment response is important for improving the prognosis in patients with hepatocellular carcinoma (HCC). The progression of HCC is related to hypercoagulability and angiogenesis. It is known that ADAMTS13 and von Willebrand factor (VWF) are related to hypercoagulability. In addition, previous study reported that the association between ADAMTS13 and VWF, and angiogenesis via vascular endothelial growth factor (VEGF). Recently, ADAMTS13 and VWF have been associated with the prognosis in patients with various kinds of cancer undergoing chemotherapy.AIMTo investigate whether ADAMTS13 and VWF become useful biomarkers of treatment response in HCC patients before the initiation of HAIC treatment.METHODSSeventy-two patients were enrolled in this study. ADAMTS13 activity (ADAMTS13:AC), VWF antigen (VWF:Ag) and VEGF levels were determined via enzyme-linked immunosorbent assay. Univariable and multivariable analyses were performed to determine the predictive factors of treatment response in patients with HCC undergoing HAIC treatment.RESULTSADAMTS13:AC levels in HCC patients with stable disease (SD) + partial response (PR) of HAIC treatment were significantly higher than those with progressive disease (PD) (P < 0.05). In contrast, VWF:Ag/ADAMTS13:AC ratio and VEGF levels in HCC patients with SD + PR were significantly lower than those with PD (both P < 0.05). Patients with high VWF:Ag/ADAMTS13:AC ratio (> 2.7) had higher VEGF levels than those with low ratio (≤ 2.7). Multivariable analysis revealed that VWF:Ag/ADAMTS13:AC ratio was a predictive factor of HAIC treatment response.CONCLUSIONVWF:Ag/ADAMTS13:AC ratio may become a useful biomarker of treatment response in HCC patients before the initiation of HAIC treatment.     

A phase II study of extended dose temozolomide and thalidomide in previously treated patients with metastatic melanoma

Purpose To assess the efficacy and tolerability of extended dose temozolomide and continuous thalidomide in patients with advanced metastatic cutaneous melanoma.Patients and methods Eligibility criteria included adults with histologic diagnosis of metastatic melanoma with adequate organ function and performance status. Temozolomide (75 mg/m²/day) was administered for 6 weeks followed by a 2-week rest. Thalidomide (200 mg/day) was given for the first 2 weeks and increased by 100 mg/day at weekly intervals up to a maximum of 400 mg/day, if no toxicity. For patients older than 70 years, thalidomide was started at 100 mg/day and the dose was increased by 50 mg/day up to a maximum of 250 mg/day.Results Twenty-six extensively pretreated subjects, with poor prognostic factors, were entered into this study and included in all analyses. According to the RECIST criteria, one (4%) subject achieved a complete response (CR), two (8%) partial response (PR), and five (19%) stable disease (SD), for a response rate (CR + PR) of 12% [95% confidence interval (CI), 0–24.7%] and a clinical benefit (CR + PR + SD) of 31%. Median time to progression was 1.8 months (95% CI, 1.2–2.4 months) and median survival was 5.2 months (95% CI, 4.1–6.2 months).Conclusions The combination of temozolomide and thalidomide is well tolerated in patients with very advanced heavily pretreated metastatic melanoma. It has modest activity in this population with grave prognosis.     

Nephrotic-range proteinuria in patients with renovascular disease

PURPOSE: Proteinuria is usually considered a manifestation of glomerular disease. We sought to describe the characteristics of patients with nephrotic-range proteinuria resulting from renovascular disease and to compare them with those of patients who had glomerulonephritis. SUBJECTS AND METHODS: We identified 14 patients with nephrotic-range proteinuria and renovascular disease and compared them with 14 patients who had nephrotic-range proteinuria and biopsy-proven glomerulonephritis, matched for sex, age, and glomerular filtration rate. RESULTS: Patients with renovascular disease were more likely to have known atherosclerotic vascular disease [13 of 14 (93%) vs 3 of 14 (21%), P < 0.0001) and were usually smokers [12 of 14 (85%) vs 3 of 14 (21%), P < 0.0001]. They also had a greater mean (+/- SD) difference between the lengths of their kidneys (29 +/- 10 vs 5 +/- 5 mm, P < 0.001); greater systolic blood pressure (203 +/- 22 vs 174 +/- 25 mm Hg, P < 0.005), plasma renin activity (17 +/- 19 vs 2 +/- 2 ng/mL/h, P = 0.005), and plasma aldosterone concentration (40 +/- 23 vs 11 +/- 10 ng/dL, P = 0.0001); and lower serum potassium levels (3.3 +/- 0.5 vs 3.8 +/- 0.5, P <0.05). Effective renal plasma flow was lower (139 +/- 68 vs 307 +/- 185 mL/min/1.73 m3) and filtration fraction was markedly greater (0.28 +/- 0.04 vs 0.15 +/- 0.07, P = 0.0001) in the patients with renovascular disease. After the oral administration of captopril, blood pressure, effective renal plasma flow, and glomerular filtration rate decreased only among patients with renovascular disease. Of the 14 patients with renovascular disease, 13 had evidence of renal artery thrombosis seen at angiography; 2 patients required dialysis, and 3 others died during follow-up. CONCLUSION: Our findings suggest that the patients with nephrotic-range proteinuria resulting from renovascular disease have distinct characteristics and a poor prognosis.     

Thalidomide in multiple myeloma: lack of response of soft-tissue plasmacytomas

Thalidomide is active in patients with refractory myeloma. Seventeen patients (nine men/eight women, median age 73 years) with multiple myeloma (MM) were treated with thalidomide. Fifteen patients had refractory disease and two untested relapse. The median dose of thalidomide was 500 mg (range, 200-800 mg). Nine of the 17 patients (53%) responded. The response rate was significantly higher in patients with no extramedullary disease than in those with soft tissue masses (75% CI: 43-95% versus 0%; P = 0.01)). Of note, no decrease in the size of soft tissue plasmacytomas was observed in all the five patients who had extramedullary involvement. This data suggests that the mechanism of action and effectiveness of thalidomide might depend on the site of the tumour cells.     

Thalidomide therapy for patients with refractory Crohn's disease: an open-label trial

BACKGROUND & AIMS: Inhibition of tumor necrosis factor is a proposed mechanism for the anti-inflammatory properties of thalidomide. We performed an open-label trial of thalidomide in refractory Crohn's disease. METHODS: Twenty-two patients with refractory Crohn's disease (Crohn's Disease Activity Index [CDAI] > 200 and/or draining perianal disease) initiated therapy with thalidomide, 200 mg at bedtime (18 patients), or 300 mg at bedtime (4 patients). CDAI and goal interval scores (GIS) were assessed at weeks 0, 4, and 12. Clinical response for patients with luminal disease was defined as reduction in CDAI score of >150 points and for fistula patients was 2 scores of >/=1+ in 3 parameters of the GIS. Clinical remission was defined as a total CDAI < 150 (luminal patients) or >/=2+ for all parameters of the GIS (fistula patients). RESULTS: Nine patients with luminal disease and 13 with fistulas (16 male, 6 female) were enrolled. The median CDAI score at entry was 371 (95-468). Sixteen patients completed 4 weeks of treatment (12 clinical responses, 4 clinical remissions). All 14 patients completing 12 weeks met criteria for clinical response. Nine achieved clinical remission (3 luminal, 6 fistula patients). The median CDAI score was 175 (30-468; P < 0.001 vs. baseline). CONCLUSIONS: Thalidomide is efficacious in some patients with refractory Crohn's disease.     

Intravenous melphalan, thalidomide and prednisone in refractory and relapsed multiple myeloma

OBJECTIVES: Thalidomide combined with conventional chemotherapies including oral melphalan shows significant anti-myeloma activity. To address this issue, feasibility and efficacy of a three drug combination consisting of intravenous (i.v.) melphalan, thalidomide and prednisone [M(i.v.)PT] was evaluated in advanced myeloma patients. PATIENTS AND METHODS: Twenty-four advanced myeloma patients were treated with multiple cycles of a regimen consisting of low dose i.v. melphalan (20 mg/m2) at d 1, thalidomide at the dose of 50-100 mg/d given continuously and oral prednisone at the planned dose of 50 mg/d every other day. Intravenous melphalan was administered every fourth month. Median time from diagnosis was 40 months (range: 8-144 months). Fifteen patients (66%) had previously been treated with a combination of thalidomide and dexamethasone or with thalidomide alone. RESULTS: Overall, on an intent-to treat basis, 14 patients responded: three achieved near complete remission (nCR), seven achieved partial response (PR), four minimal response (MR). Six patients showed stable disease (SD) and four-disease progression. Interestingly, of five patients who had previously progressed while on thalidomide and prednisone, one reached nCR, two PR and one MR. After a median follow up of 14 months, median progression free survival was 9 months. Response duration was longer than that induced by the previous line of treatment in eight patients (33%). Thalidomide-associated toxicity mainly consisted of constipation, tingling and sedation. CONCLUSIONS: M(i.v.)PT is an effective regimen, which can overcome resistance to thalidomide plus prednisone in advanced myeloma with acceptable toxicity.     

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the prognostic factors and efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. METHODS: Fifty hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) were treated using hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted port. The epirubicin-cisplatin-5-fluorouracil (ECF) chemotherapeutic regimen consisted of 35 mg/m 2 epirubicin on day 1, 60 mg/m 2 cisplatin for 2 h on day 2, and 500 mg/m 2 5-fluorouracil for 5 h on days 1-3. The treatments were repeated every 3 or 4 wk. RESULTS: Three (6%) of the 50 patients achieved a complete response (CR), 13 (26%) showed partial responses (PR), and 22 (44%) had stable disease (SD).The median survival and time to progression were 7 and 2 mo, respectively. After 2 cycles of HAIC, CR was achieved in 1 patient (2%), PR in 10 patients (20%) and SD in 26 patients (52%). Significant pre-treatment prognostic factors were a tumor volume of < 400 cm 3 (P = 0.01) and normal levels of protein induced by vitamin K absence or antagonist (PIVKA)-Ⅱ (P = 0.022). After 2 cycles of treatment, disease control (CR + PR + SD) (P = 0.001), PVTT response (P = 0.003) and α-fetoprotein reduction of over 50% (P = 0.02) were independent factors for survival. Objective response (CR + PR), disease control, PVTT response, and combination therapy during the HAIC were also significant prognostic factors. Adverse events were tolerable and successfully managed. CONCLUSION: HAIC may be an effective treatment modality for advanced HCC with PVTT in patients with tumors < 400 cm 3 and good prognostic factors.     

反流性食管炎与非糜烂性反流病食管酸暴露的特点比较

目的　比较反流性食管炎 (RE)与非糜烂性反流病 (NERD)各亚组食管酸暴露特点。方法　具有典型反酸 烧心等症状的 12 8例患者 ,经胃镜等系统检查诊断为胃食管反流病 (GERD)。便携式 pH监测仪行胃食管 2 4hpH监测 ,DeMeester积分≥ 15分为存在病理性酸反流。 结果　 12 8例患者中 ,37例 (2 8 9% )存在RE ,91例 (71 1% )为NERD。pH监测阳性在RE组和NERD组中分别为 2 5例 (6 7 6 % )和 4 6例 (5 0 5 % ) ,差异无统计学意义 ;两组DeMeester积分均值差异亦无统计学意义 (5 3 4 5± 6 2 0 4比 4 0 0 4± 6 1 80 ,P >0 0 5 )。RE组长反流次数显著高于NERD组 (8 16±10 2 7比 3 96± 6 87,P =0 0 0 4 )。以症状指数 >5 0 %为阳性 ,NERD阳性组 (pH值监测异常 )症状指数阳性率显著高于NERD阴性组 (pH值监测正常 ) (43 5 %比 15 6 % ,P <0 0 0 1)。NERD阴性组中具有阳性症状指数的患者 7例 (15 6 % ) ,阴性症状指数者 38例。前者总反流次数及立位反流时间百分比显著高于后者。RE患者中 ,12例 pH监测阴性者食管及胃内pH的中位值显著高于 pH监测阳性者。结论　RE患者长反流发生率高于NERD患者 ;症状的发生与酸反流相关 ;NERD患者根据酸反流与症状关系可分为不同的亚组。RE阴性组可能存在混合反流或胆汁反流     

Curative efficacy might be an early predictor of prognosis in patients with small cell lung cancer treated with 2 cycles of platinum-based first-line chemotherapy

BackgroundPlatinum-based chemotherapy remains the essential therapy for small cell lung cancer (SCLC). Here, we conducted a statistical analysis to explore whether the curative efficacy of 2-cycle platinum-based chemotherapy can predict the survival of patients with SCLC.MethodsFifty-six SCLC patients who had each received 2 cycles of platinum-based chemotherapy were enrolled. The curative efficacy of the chemotherapy was evaluated, mainly by chest computed tomography, and the treatment response was categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patients were continuously followed up for progression-free survival (PFS) and overall survival. The 55 patients were separated into 2 groups by the curative efficacy of the 2-cycle first-line platinum-based chemotherapy. All statistical analyses were performed with SPSS software (version 17.0; SPSS, Inc.; Chicago, IL, USA)ResultsPatients who responded to 2-cycle chemotherapy (partial response, PR) had significantly better survival than others who did not (stable disease, SD or progressive disease, PD). The median progression-free survival (mPFS) in the PR group was 6.330 months, which was significantly longer than the 2.870 months seen in SD+PD group (95% CI: 4.631–8.029 vs. 0.000–5.790, P=0.022). The median overall survival (mOS) was 10.870 months in the PR group, which was remarkably longer than the 8.970 months observed in the SD+PD group (95% CI: 9.546–12.194 vs. 6.517–11.423, P=0.028). Curative efficacy had no correlation with clinical features.ConclusionsThe curative efficacy of 2-cycle first-line platinum-based chemotherapy was significantly correlated with PFS and OS, and showed prognostic value in SCLC patients. Patients who were sensitive to chemotherapy had superior survival to those who were chemotherapy insensitive.     

Neurological toxicity of long-term (>1 yr) thalidomide therapy in patients with multiple myeloma

OBJECTIVE: Thalidomide is remarkably active in advanced relapsed and refractory multiple myeloma (MM), so that its use has been recently proposed either in newly diagnosed patients or as maintenance treatment after conventional or high-dose therapy. This latter therapeutic approach has risen the concern of side-effects of long-term therapy with this drug. METHODS: We analysed long-term toxicity of 40 patients (27 M, 13 F, median age = 61.5 yr) who received salvage therapy with thalidomide +/- dexamethasone for longer than 12 months (median 15, range 12-44) at our centre. All the patients had achieved at least a stable disease upon treatment with thalidomide alone (200-400 mg/d, n = 20) or thalidomide (200 mg/d) and dexamethasone (40 mg/d for 4 d every 4 wk) (n = 20). RESULTS AND CONCLUSIONS: Neurotoxicity was the most troublesome and frequent toxic effect that was observed after long-term treatment, the incidence averaging 75%. Among these 30 patients symptoms included paraesthesias, tremor and dizziness. Neurotoxicity was grade 1 in six patients (15%); grade 2 in 13 patients (32.5%), thus determining thalidomide dose reduction to 100 mg/d; and grade 3 in 11 patients (27.5%) who had subsequently to interrupt therapy despite their response. Electromyographic study, performed in patients with grade >/=2 neurotoxicity, revealed a symmetrical, mainly sensory peripheral neuropathy, with minor motor involvement. The severity of neurotoxicity was not related to cumulative or daily thalidomide dose, but only to the duration of the disease prior to thalidomide treatment, although no patients presented neurological symptoms at study entry. These results suggest that long-term thalidomide therapy in MM may be hampered by the remarkable neurotoxicity of the drug, and that a neurological evaluation should be mandatory prior to thalidomide treatment, in order to identify patients at risk of developing a peripheral neuropathy.     

Long-term results of thalidomide in refractory and relapsed multiple myeloma with emphasis on response duration

OBJECTIVE: Thalidomide administered as a single agent produces a response rate of about 40% in patients with refractory or relapsed multiple myeloma (MM). The aim of our study was to determine the quality and duration of such responses. PATIENTS AND METHODS: Forty-two consecutive patients with refractory (20) or relapsed (22) MM were given thalidomide as a single agent at our institution. Most of them (70%) had previously received two or more lines of therapy, and 38% had undergone autologous stem cell transplantation. RESULTS: Eighteen patients (43%) responded to thalidomide [11 minimal responses (MR) and seven partial responses (PR)] according to the European Marrow Transplant Registry (EBMT) criteria. The median time to response was 3 months and the median duration of therapy in responding patients was 9 months. Treatment was discontinued because of toxicity in 10 responding patients. The toxicity mainly led to peripheral neuropathy and fatigue. At the time of this analysis, all responding patients had progressed except one who remains in continued stable PR. The median time to progression was 15.6 months (range 1.3 to 70+), with a trend towards a longer duration for patients who achieved PR vs. MR (21.2 vs. 11.2 months, P = 0.11). The median duration of response was 12.4 months (range: 0.3-67+) (17.2 months for PR vs. 9.7 months for MR, P = 0.11). CONCLUSION: These results show that the effect of thalidomide in refractory/relapsed MM can be sustained, particularly in patients who achieve a greater degree of response, and support the finding that this drug can be used for maintenance therapy.     

Thalidomide for the treatment of resistant cutaneous lupus: efficacy and safety of different therapeutic regimens

PURPOSE: Thalidomide is effective for the treatment of severe cutaneous lupus. Our aim was to study the safety and efficacy of different doses of thalidomide in this condition. METHODS: We studied patients with severe cutaneous lupus that was unresponsive to antimalarials, prednisolone, methotrexate, azathioprine, and cyclosporin A. Starting doses of 100 mg daily (n = 16 patients), 50 mg daily (n = 17), or 50 mg on alternate days (n = 15) were compared. The response to thalidomide was categorized as complete remission, partial remission, or no visible improvement. All patients received a baseline electromyogram (EMG) followed by repeat EMG every 3 to 6 months, or sooner if neuropathic symptoms developed. RESULTS: Forty-eight patients (46 female; mean [+/- SD] age, 44 +/- 12 years; range, 22 to 71 years) with discoid lupus (n = 18), subacute cutaneous lupus (n = 6), or systemic lupus erythematosus with skin involvement (n = 24) were included. The response rate was 81%, including 29 patients (60%) in complete remission and 10 (21%) in partial remission. Nine patients (19%) failed to respond. Thirteen patients (27%) developed peripheral neuropathy, which was EMG-proven in 11, including 4 patients in the 50-mg alternate-day group. Other side effects included drowsiness, constipation or abdominal pain, and amenorrhea. The relapse rate after stopping thalidomide was 67% (26/39). There was no association between a positive response to the drug and either starting doses or cumulative dose. Similarly, no association was found between peripheral neuropathy and the starting or cumulative dose. CONCLUSION: Thalidomide is effective for the treatment of severe cutaneous lupus. There were no clear dose-dependent effects. However, the high incidence of neurotoxicity, even at low doses, suggests that it may be most useful as a remission-inducing drug.     

Frequent good partial remissions from thalidomide including best response ever in patients with advanced refractory and relapsed myeloma

Twenty-three patients with advanced and heavily pretreated myeloma were treated with thalidomide. Starting dose was 200 mg/d, and 20 patients had dose escalations up to 400 (n = 5), 600 (n = 12) or 800 mg/d (n = 3), usually in divided doses. Nineteen patients were refractory to recent chemotherapy, and four had untreated relapse after prior intensive therapy. Ten out of 23 patients (43%) achieved partial response (PR; nine with refractory and one with relapsed disease), six patients had minor response or stabilization of the disease and four had disease progression. Another three patients died early from advanced myeloma at less than 3 weeks of thalidomide therapy. Of the 10 patients with PR, seven had a better response than after any prior therapy, despite vincristine-doxorubicin-dexamethasone (VAD)-based treatment in all but one and high-dose melphalan with autologous stem cell support in four. Time to achieve PR was rapid in patients receiving thalidomide in divided doses (median 31 d). Responses also included reduced bone marrow plasma cell infiltration and improved general status. Normalized polyclonal gammaglobulin levels were seen in four cases. Six out of 10 patients with PR remained in remission with a median time on treatment of 23 weeks (range 15-50 weeks). Sedation was common but usually tolerable, and some patients continued full- or part-time work. Four patients had skin problems, three patients had pneumonia, one hypothyrosis, one sinus bradycardia and one minor sensory neuropathy. Thalidomide may induce good partial remissions in advanced refractory myeloma with tolerable toxicity, and should be evaluated in other settings for myeloma patients. Divided thalidomide doses seem to reduce time to achieve remission and may improve response rate.     

Effect of antimalarial agents on the fasting lipid profile in systemic lupus erythematosus

OBJECTIVE: To ascertain the relative effect of antimalarial (AM) agents on fasting lipid fractions in patients with systemic lupus erythematosus (SLE). METHODS: The study was cross sectional including all patients with SLE who were seen in our lupus clinic with fasting lipid profiles measured as part of evaluation from November 1995 to March 1999. RESULTS: A total of 123 patients with a mean age of 45.3 years and mean disease duration 13.4 years were studied; 73.2% were taking prednisone with a mean +/- SD dose of 10.9 +/- 9.2 mg/day, 48.0% were taking AM, and 30.8% were taking both. In the entire group, patients taking AM had a 12.5% lower total cholesterol (TC) (5.11 +/- 1.27 vs 5.84 +/- 1.23; p = 0.002), 22.1% lower very low density lipid-cholesterol (VLDL-C) (0.66 +/- 0.40 vs 0.85 +/- 0.39; p = 0.01), and 15.7% lower LDL-C (3.01 +/- 1.14 vs 3.58 +/- 1.10; p = 0.007). For patients taking prednisone, those taking concomitant AM (n = 38) had significantly lower TC (5.26 +/- 1.30 vs 5.99 +/- 1.29; p = 0.01), VLDL-C (0.65 +/- 0.39 vs 0.85 +/- 0.41; p = 0.02), and LDL-C (3.05 +/- 1.20 vs 3.69 +/- 1.09; p = 0.01) than those without AM (n = 48). For patients taking < or = 10 mg/day prednisone, TC (4.69 +/- 0.88 vs 5.74 +/- 1.20; p < 0.001), VLDL-C (0.61 +/- 0.37 vs 0.83 +/- 0.44; p = 0.05), and LDL-C (2.57 +/- 0.76 vs 3.49 +/- 1.04; p < 0.001) were still lower in patients with concomitant AM (n = 22) than those without AM (n = 36). CONCLUSION: TC, VLDL-C, and LDL-C levels were significantly lower in patients taking AM, including patients taking concomitant prednisone. Thus AM may have beneficial effects in SLE in addition to disease suppression.     

Effect of preoperative transcatheter arterial chemoembolization on proliferation of hepatocellular carcinoma cells

AIM To evaluate the effect of preoperative transcatheter arterial chemoembolization (TACE) on proliferation of hepatocellular carcinoma (HCC) cells.METHODS A total of 136 patients with HCC underwent liver resection. Of 136 patients, 79 patients received 1 to 5 courses of TACE prior to liver resection (TACE group),who were further subdivided into four groups Group A (n = 11) who received 1 to 4 courses of chemotherapy alone; Group B (n = 33) who received 1 to 5 courses of chemotherapy combined with iodized oil; Group C (n = 23) who received 1 to 3 courses of chemotherapy combined with iodized oil and gelatin sponge; and Group D (n = 12) who received 1 to 3 courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge.The other 57 patients only received liver resection (nonTACE group). The expressions of Ki-67 and proliferating cell nuclear antigen (PCNA) protein were detected in the liver cancer tissues by immunohistochemical method.RESULTS The Ki-67 protein expression was significantly lower in Groups C and D as compared with non-TACE group (31.35% ± 10.85% vs 44.43% ± 20.70%,30.93% ± 18.10% vs 44.43% ± 20.70%, respectively, P ＜ 0.05). The PCNA protein expression was significantly lower in Groups C and D as compared with non-TACE group (49.61% ± 15.11% vs 62.92% ± 17.21%, 41.16% ± 11.83% vs 62.92% ± 17.21%, respectively, P ＜ 0.05).The Ki-67 protein expression was significantly higher in Group A as compared with non-TACE group (55.44% ± 13.72% vs 44.43% ± 20.70%, P ＜ 0.05). The PCNA protein expression was significantly higher in Groups A and B as compared with non-TACE group (72.22% ± 8.71% vs 62.92% ± 17.21%, 69.91% ± 13.38% vs 62.92% ± 17.21%, respectively, P ＜0.05).CONCLUSION Preoperative multi-material TACE suppresses the proliferation of HCC cells, while a single material embolization and chemotherapy alone enhance the proliferation of HCC cells.     

Efficacy of platinum analogue for advanced hepatocellular carcinoma unresponsive to transcatheter arterial chemoembolization with epirubicin

Aim:  Hepatocellular carcinoma (HCC) often shows resistance to transcatheter arterial chemoembolization (TACE). Such patients often have a poor prognosis and are unresponsive to other forms of therapy. The aim of this retrospective study was to determine the response to TACE using platinum analogues in patients deemed resistant to TACE using epirubicin.
Methods:  We studied 152 consecutive patients with advanced HCC resistant to TACE using epirubicin. All cases were treated with platinum analogue using transcatheter arterial chemotherapy with or without embolization.
Results:  Computed tomography at 3 months after therapy showed complete response (CR) in 6 patients (4.0%), partial response (PR) in 28 (18%), stable disease (SD) in 35 (23%), and progressive disease (PD) in 83 (55%). The cumulative survival rates for PR/CR patients who received platinum analogue-transcatheter arterial chemotherapy with or without embolization (81.8% at first year, 53.9% at second year, and 33.1% at third year) were significantly higher than those of SD/PD patients (36.6%, 17.5% and 7.4%, respectively) ( P  < 0.001). The 50% survival period was extended almost 1.4 year in PR/CR patients who received platinum analogue-transcatheter arterial chemotherapy with or without embolization.
Conclusion:  Our retrospective study is the first to report the efficacy of platinum analogues for advanced HCC unresponsive to TACE using epirubicin.