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PubMed2006

Influence of applied quantity of sunscreen products on the sun protection factor--a multicenter study organized by the DGK Task Force Sun Protection.

It is often debated that the protection against solar-induced erythema under real conditions is dependent upon the amount of sunscreen applied. It is believed that when too little is applied a lower sun protection than indicated on the label will result. The aim of this study was to quantify this effect. In this multicenter study, the influence of three different amounts (0.5, 1.0, 2.0 mg/cm(2)) of three commercial sunscreen products in three reliable test centers was investigated according to the test protocol of The International Sun Protection Factor Test Method. The main result was a linear dependence of the SPF on the quantity applied. Taking into consideration the volunteer-specific variations, an exponential dependence of confidence interval of the in vivo SPF and amount applied was found. The highest amount applied (2.0 mg/cm(2)) was linked to the lowest confidence intervals. Thus, from the point of view of producing reliable and reproducible in vivo results under laboratory conditions, the recommendation of this multicenter study is an application quantity of 2.0 mg/cm(2).

Confidence Intervals↗

PubMed2006

The multicenter trial SAKK 37/95 of cladribine, cyclophosphamide and prednisone in the treatment of chronic lymphocytic leukemias and low-grade non-Hodgkin's lymphomas.

A multicenter trial was performed to confirm the therapeutic efficacy and the toxicity profile of the combination of cladribine, cyclophosphamide and prednisone in low-grade non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Twenty-three adults with previously treated (61%) or untreated (39%) NHL International Working Formulation A or Binet B and C CLL were administered cladribine 0.1 mg/kg/day as a subcutaneous bolus for 5 days, intravenous cyclophosphamide 500 mg/m2 on day 1, and oral prednisone 40 mg/m2 on days 1-5, every 4 weeks. Unexpected early hematological toxicities led to dose modifications for pretreated patients who received cladribine for 3 days only up to a maximum of five courses. Responses were observed in 75%, with 7 patients obtaining a complete clinical and hematological response. Median duration of complete response was 9 months. Median time to progression or relapse was 31 months. Myelosuppression and infections were dose limiting whereas posttreatment complications, including fatalities, resulted from infections. Median overall survival time from trial entry was 60 months. Activity of the combination of cladribine, cyclophosphamide and prednisone was confirmed. However, in the specific setting of a multicenter trial, unexpected fatal infectious episodes occurred in pretreated patients. Great caution is thus required in these susceptible patients and the routine use of corticosteroids should probably be abandoned.

Aged↗

PubMed1992

Effectiveness and safety of recombinant human erythropoietin in predialysis patients. Austrian Multicenter Study Group of r-HuEPO in Predialysis Patients.

Experience with erythropoietin in the treatment of anemia in predialysis patients is limited. A practical treatment regimen which minimized the number of outpatient visits was investigated. The Austrian multicenter study included 123 patients. At baseline, the treatment protocol mandated once weekly the administration of 10,000 U recombinant human erythropoietin (r-HuEPO) subcutaneously. The follow-up period was 3 months, and dose adjustments were made at montly intervals. At baseline, the mean values for creatinine were 6.2 +/- 0.2 mg/dl, and for hemoglobin (Hb) 9.0 g/dl. During 3 months of therapy, mean Hb increased to 10.8 g/dl and creatinine to 6.6 mg/dl. The initial r-HuEPO weekly dose was 10,000 U. The mean dose after 3 months was 9,000 +/- 4,000 U. There was no significant alteration of the slope of the reciprocal creatinine curve or of blood pressure values. No side effects occurred during the 3-month treatment period. In conclusion, the results of this multicenter trial demonstrate that using a simple once-weekly subcutaneous treatment regime, r-HuEPO can be administered safely and effectively in predialysis patients.

Adolescent↗

PubMed1999

Multicenter clinical trial to evaluate the efficacy of correction for photon attenuation and scatter in SPECT myocardial perfusion imaging.

BACKGROUND: Soft tissue attenuation is a prominent cause of single-photon emission computed tomography (SPECT) imaging artifacts, which may result in reduced diagnostic accuracy of myocardial perfusion imaging. A method incorporating simultaneously acquired transmission data permits nonuniform attenuation correction and when incorporating scatter correction and resolution compensation may substantially reduce interpretive errors. METHODS AND RESULTS: A prospective multicenter trial was performed recruiting patients with angiographically documented coronary disease (n=96) and group of subjects with a low likelihood of disease (n=88). The uncorrected and attenuation/scatter corrected images were read independently, without knowledge of the patient's clinical data. The detection of >/=50% stenosis was similar using uncorrected perfusion data or with attenuation/scatter correction and resolution compensation (visual or visual plus quantitative analysis), 76% versus 75% versus 78%, respectively (P=NS). The normalcy rate, however, was significantly improved with this new methodology, using either the corrected images (86% vs 96%; P=0.011) or with the corrected data and quantitative analysis (86% vs 97%; P=0.007). The receiver operator characteristic curves were also found to be marginally but not significantly higher with attenuation/scatter correction than with tradition SPECT imaging. However, the ability to detect multivessel disease was reduced with attenuation/scatter correction. Regional differences were also noted, with reduced sensitivity but improved specificity for right coronary lesions using attenuation/scatter correction methodology. CONCLUSIONS: This multicenter trial demonstrates the initial clinical results of a new SPECT perfusion imaging modality incorporating attenuation and scatter correction in conjunction with 99mTc sestamibi perfusion imaging. Significant improvements in the normalcy rate were noted without a decline in overall sensitivity but with a reduction in detection of extensive coronary disease.

Data Interpretation, Statistical↗

PubMed1994

Angiographic detection of carotid plaque ulceration. Comparison with surgical observations in a multicenter study. North American Symptomatic Carotid Endarterectomy Trial.

BACKGROUND AND PURPOSE: Carotid plaque ulceration is used as one of the determinants in deciding which patients should be submitted to carotid endarterectomy. Uncertainties about its importance persist. Its detection by angiography is an important consideration. METHODS: The detection of ulceration by angiography was compared with observations during endarterectomy in the first 500 patients recruited into the North American Symptomatic Carotid Endarterectomy Trial. This represents the first multicenter compilation of data on this subject and the largest series of patients with both arteriographic and direct surgical observation. RESULTS: Sensitivity and specificity of detecting ulcerated plaques were 45.9% and 74.1%, respectively. The positive predictive value of identifying an ulcer was 71.8%. These results remained unchanged with differing degrees of carotid stenosis and were confirmed by analyses based on receiver operating characteristic (ROC) methodology. The area under the ROC curve (Az) was estimated to be 0.61 (95% confidence interval, 0.55 to 0.67). CONCLUSIONS: These observations from a multicenter study confirm that little agreement exists between angiography and surgical observation in detecting carotid plaque ulceration.

Angiography↗

PubMed1998

Hypervolemic hemodilution in acute ischemic stroke: the Multicenter Austrian Hemodilution Stroke Trial (MAHST).

BACKGROUND AND PURPOSE: Experimental studies suggest a beneficial effect of hemodilution on acute ischemic stroke. This was not proven by previous multicenter trials in the clinical setting. Various reasons have been suggested for the failure of these studies, which we attempted to consider in the Multicenter Austrian Hemodilution Stroke Trial (MAHST). METHODS: MAHST is a randomized, double-blind, placebo-controlled study of hypervolemic hemodilution (HHD) within 6 hours of a clinically first ischemic stroke localized in the middle cerebral artery territory. The treatment consisted of 10% hydroxyethyl starch 200/0.5 (HES) and was tested against pure rehydration with Ringer's lactate over a period of 5 days. Our primary outcome measure was clinical improvement within 7 days as measured by the Graded Neurologic Scale (GNS). We performed an adaptive interim analysis to reevaluate the study goal after entering half of the projected number of patients (n = 200). At least 600 patients per group would have been required for significant results, and therefore we decided to terminate the trial. RESULTS: Ninety-eight patients received HHD and 102 patients placebo. The baseline characteristics were comparable between both groups. In the HHD group the absolute reduction of the hematocrit was 2.5% on day 2 with a maximum of 3.7% on day 5, which compares with a reduction in the placebo group of 1% and 1.9%, respectively. Intention-to-treat analysis showed no significant difference of the change of the GNS scores between HHD-treated (median, -8.5; 95% confidence interval, -14.2 to -4.0) and placebo-treated patients (median, -6.0; 95% confidence interval, -11.0 to 0.0) on day 7, and GNS scores remained similar in both treatment groups throughout the trial. At 3 months, slightly more HHD patients showed complete independence on the Barthel Index (28 versus 24), and fewer HHD than placebo patients had died (13 versus 17), but these differences were not statistically significant. HHD treatment was not associated with any specific adverse event. CONCLUSIONS: Mild HHD is safe but failed to demonstrate a significant beneficial effect over the pure rehydration regimen in patients with acute ischemic stroke.

Aged↗

PubMed1994

Long-term effects of ticlopidine on lower limb blood flow, ankle/brachial index and symptoms in peripheral arteriosclerosis. A double-blind study. The STIMS Group in Lund. Swedish Ticlopidine Multicenter Study.

The aim was to test within a randomized double-blind trial whether the platelet inhibitor ticlopidine might improve peripheral blood flow and distal pressures in patients with aortofemoral arteriosclerosis. One hundred and one patients with intermittent claudication were studied after one year, after two to three years, and after five years of treatment with ticlopidine, 500 mg/day, or placebo. Analysis was performed according to years on treatment. Baseline flow values as assessed by venous occlusion plethysmography were significantly and similarly deranged in the ticlopidine and placebo groups as compared with a reference group of healthy subjects. Ankle/brachial index was unrelated to either leg blood flow variables or walking distance. After five years of treatment (median follow-up time) a slight tendency to a slower progression of disease was observed in the ticlopidine group as compared with placebo. However, intergroup differences were not significant. Therefore, the potential benefit of ticlopidine in this respect is from a clinical point of view certainly only marginal. Minor increases in claudication distances were found with no difference between groups. Smoking habits and lipoproteins were mainly unaltered at the end of the study. It is concluded that platelet inhibition for up to five years has no clear beneficial effect on leg blood flow variables, ankle/brachial index, or walking distances and probably no clinically relevant retarding effect on the slow progression of atherosclerosis. This lack of influence must be distinguished from the antithrombotic effect of ticlopidine, shown as a decreased incidence of acute cardiovascular events and mortality in the authors' multicenter study, STIMS (the Swedish Ticlopidine Multicenter Study).

Adult↗

PubMed1997

Perindopril/hydrochlorothiazide dose combinations for the treatment of hypertension: a multicenter study.

The primary goal of combination therapy is to enhance efficacy without compromising safety. In this multicenter study, the efficacy and tolerability of perindopril added to continuing hydrochlorothiazide therapy were evaluated in patients with mild to moderate (stage I and II), essential hypertension. Two hundred fifty-two patients with supine diastolic blood pressure of 95 mmHg to 114 mmHg were treated for 4 weeks with open-label hydrochlorothiazide at 25 mg/day. The 208 patients whose supine diastolic blood pressure was > or = 90 mmHg at the end of hydrochlorothiazide monotherapy entered a 12-week, double-blind treatment, where placebo or perindopril were added to the 25-mg/ day hydrochlorothiazide therapy as follows: placebo (n = 50) and doses of perindopril at 2 mg/day (n = 52), 4 mg/day (n = 53), and 8 mg/day (n = 53). The perindopril-hydrochlorothiazide combinations decreased both supine systolic blood pressure and supine diastolic blood pressure by 10.3/6.7, 9.6/8.0, and 9.3/6.3 mmHg, for perindopril doses of 2, 4, and 8 mg/day, respectively; there was no difference among the three drug groups. Placebo decreased blood pressure by 1.6/2.0 mmHg, an effect that was significantly lower compared with perindopril-hydrochlorothiazide combinations. Adverse events were mild and similar among all treatment groups, except cough, which was 4.0%, 3.9%, 7.6%, and 13.2% for placebo and perindopril doses of 2, 4, and 8 mg, respectively. The results of this multicenter study indicate that the combination of perindopril and hydrochlorothiazide is safe and effective in lowering blood pressure. The findings also demonstrate that lower doses of perindopril are as effective as higher doses when combined with hydrochlorothiazide.

Adult↗

PubMed2026

Continuous Intravenous Lidocaine for Refractory Cancer Pain in Palliative Care: A Multicenter Feasibility Study.

ObjectivesTo assess the feasibility and tolerability of continuous low-dose intravenous lidocaine infusion in patients with opioid-refractory cancer pain receiving palliative care, and to explore its potential impact on pain outcomes in real-world clinical conditions.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled feasibility study in palliative care units to evaluate continuous intravenous lidocaine infusion in patients with opioid-refractory cancer pain. Patients were randomized to receive lidocaine (5 mg/kg/day, increased to 8 mg/kg/day if pain reduction was <30% after 24 h) or placebo for 48 h. Pain intensity was assessed using the Numeric Pain Intensity Scale, with a clinically meaningful response defined as a ≥30% reduction from baseline at 40 min. Secondary outcomes included pain evolution over time, neuropathic pain, symptom burden, and tolerability.ResultsThirty-five patients were included in the final analysis (18 lidocaine, 17 placebo). No significant difference was observed between lidocaine and placebo for the primary endpoint or for secondary pain outcomes. Reductions in pain intensity were observed in both groups. In the lidocaine group, 61% of patients required dose escalation to 8 mg/kg/day. Continuous intravenous lidocaine infusion was generally well tolerated, with mostly mild adverse events and no unexpected toxicity.ConclusionIn this multicenter feasibility study, continuous low-dose intravenous lidocaine did not demonstrate a clinically meaningful analgesic benefit over placebo. As the planned sample size was not reached, the study was underpowered. These findings highlight the challenges of randomized trials in palliative care and may inform future feasibility-oriented designs.

Humans↗

PubMedDate not supplied

Factor structure and reliability of the Alzheimer's Disease Assessment Scale in a multicenter trial with linopirdine.

The Alzheimer's Disease Assessment Scale (ADAS) has assumed a primary role in assessment of treatment responses in large-scale multicenter trials of drugs being evaluated for treatment of dementia in elderly patients. Data from 280 patients with Alzheimer's disease were analyzed to evaluate factor structure and reliability. Results confirm the presence of three primary factors interpreted as mental status, verbal fluency, and praxis. The presence of a large general factor underlying those more specific dimensions also supports the utility of the composite ADAS cognitive score that has been used as a primary outcome measure in previous drug trials. Test-retest reliability of the factor scores were calculated to be 0.83, 0.78, and 0.87. Test-retest reliability of the composite ADAS cognitive score was 0.90. Statistics useful for estimation of sample sizes for future multicenter trials are provided.

Aged↗

PubMedDate not supplied

Tumor-biological factors uPA and PAI-1 as stratification criteria of a multicenter adjuvant chemotherapy trial in node-negative breast cancer.

In axillary node-negative primary breast cancer, 70% of the patients will be cured by locoregional treatment alone. Therefore, adjuvant systemic therapy is only needed for those 30% of node-negative patients who will relapse after primary therapy and eventually die of metastases. Traditional histomorphological and clinical factors do not provide sufficient information to allow accurate risk group assessment in order to identify node-negative patients who might benefit from adjuvant systemic therapy. In the last decade various groups have reported a strong and statistically independent prognostic impact of the serine protease uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1) in node-negative breast cancer patients. Based on these data, a prospective multicenter therapy trial in node-negative breast cancer patients was started in Germany in June 1993, supported by the German Research Association (DFG). Axillary node-negative breast cancer patients with high levels of either or both proteolytic factors in the tumor tissue were randomized to adjuvant CMF chemotherapy versus observation only. Recruitment was continued until the end of 1998, by which time 684 patients had been enrolled. Since then, patients have been followed up in order to assess the value of uPA and PAI-1 determination as an adequate selection criterion for adjuvant chemotherapy in node-negative breast cancer patients. This paper reports on the rationale and design of this prospective multicenter clinical trial, which may have an impact on future policies in prognosis-oriented treatment strategies.

Biomarkers, Tumor↗

PubMed2002

High rate of clinical and molecular remissions in follicular lymphoma patients receiving high-dose sequential chemotherapy and autografting at diagnosis: a multicenter, prospective study by the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

Single-center experiences have shown that intensified treatments with autologous transplantation are a promising therapeutic strategy for patients with high-risk follicle-center lymphoma (FCL) at diagnosis, whereas data from prospective multicenter trials are still lacking. This paper describes the results of a prospective multicenter study of an intensified purging-free high-dose sequential (i-HDS) chemotherapy schedule with peripheral blood progenitor cell (PBPC) autografting. The main feature of this program is harvesting stem cells after intensified chemotherapeutic debulking, with no ex vivo manipulation of PBPCs. Ninety-two previously untreated patients aged 60 or younger with advanced-stage FCL were enrolled by 20 Italian centers and evaluated on an intention-to-treat basis. i-HDS proved feasible with limited toxicity (87% patients completed the planned treatment schedule). i-HDS led to a complete remission rate of 88%. The projected overall survival and disease-free survival (DFS) were, respectively, 84% and 67% at 4 years. Centralized molecular analysis showed that polymerase chain reaction-negative harvests could be collected in 47% of cases. Following autograft, 65% of molecularly evaluable patients achieved clinical and molecular remission. The projected DFS at 4 years of this subgroup is 85%. This result emphasizes the importance of achieving maximal tumor reduction in these patients. In conclusion, our data show that highly effective intensified treatments can now be routinely offered to young patients with poor-risk FCL even at small institutions, with no need for sophisticated and expensive cell manipulation procedures.

Adult↗

PubMed2006

A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease.

Treatment for steroid-resistant acute graft-versus-host disease (GVHD) has had limited success. ABX-CBL is a hybridoma-generated murine IgM monoclonal antibody against the CD147 antigen, weakly expressed on human leukocytes and up-regulated on activated lymphocytes. A prospective, multicenter, open-label, randomized clinical trial comparing ABX-CBL to antithymocyte globulin (ATG) for treatment of steroid-resistant acute GVHD was conducted in 95 patients at 21 centers. Forty-eight patients received ABX-CBL daily for 14 consecutive days followed by up to 6 weeks of ABX-CBL twice weekly. Forty-seven patients received equine ATG, 30 mg/kg every other day for a total of 6 doses with additional courses as needed. By day 180, overall improvement was similar in the patients receiving ABX-CBL and in those receiving ATG (56% versus 57%, P = .91). Patient survival at 18 months was less favorable on ABX-CBL than on ATG (35% versus 45%), with the 95% confidence interval ruling out that ABX-CBL provides at least a 10.4% improvement. Data from this trial suggest that ABX-CBL does not offer an improvement over ATG in the treatment of acute steroid-resistant GVHD. This prospective, multicenter, randomized clinical trial for steroid-resistant acute GVHD serves as a model for future evaluation of new agents.

Adolescent↗

PubMed2001

Determinants of patient recruitment in a multicenter clinical trials group: trends, seasonality and the effect of large studies.

BACKGROUND: We examined whether quarterly patient enrollment in a large multicenter clinical trials group could be modeled in terms of predictors including time parameters (such as long-term trends and seasonality), the effect of large trials and the number of new studies launched each quarter. We used the database of all clinical studies launched by the AIDS Clinical Trials Group (ACTG) between October 1986 and November 1999. Analyses were performed in two datasets: one included all studies and substudies (n = 475, total enrollment 69,992 patients) and the other included only main studies (n = 352, total enrollment 57,563 patients). RESULTS: Enrollment differed across different months of the year with peaks in spring and late fall. Enrollment accelerated over time (+27 patients per quarter for all studies and +16 patients per quarter for the main studies, p < 0.001) and was affected by the performance of large studies with target sample size > 1,000 (p < 0.001). These relationships remained significant in multivariate autoregressive modeling. A time series based on enrollment during the first 32 quarters could forecast adequately the remaining 21 quarters. CONCLUSIONS: The fate and popularity of large trials may determine the overall recruitment of multicenter groups. Modeling of enrollment rates may be used to comprehend long-term patterns and to perform future strategic planning.

Clinical Trials as Topic↗

PubMed1993

Multicenter phase II trial of mitoxantrone in patients with advanced nasopharyngeal carcinoma in Southeast Asia: an Asian-Oceanian Clinical Oncology Association Group study.

PURPOSE: Patients with advanced nasopharyngeal carcinoma (NPC) have a high incidence of recurrence and often develop distant metastases despite local control. This prospective multicenter phase II trial was conducted to evaluate the safety and efficacy of Novantrone (mitoxantrone; Lederle Laboratories, Wayne, NJ) in the therapy of patients with advanced NPC. PATIENTS AND METHODS: One hundred eight patients with advanced NPC, namely, those with recurrent or persistent disease following primary radiotherapy, or newly diagnosed metastatic disease, were treated with mitoxantrone. Mitoxantrone was administered intravenously at an initial dose of 12 mg/m2 and repeated every 3 weeks, with dose escalation to a maximum of 14 mg/m2. The distribution of histologic subtypes was representative of NPC, with the majority being (61%) undifferentiated (or anaplastic) carcinoma. RESULTS: The overall response rate (complete response [CR] and partial response [PR]) was 25% (95% confidence interval, 17% to 33%). The median response duration, time to treatment failure, and survival duration were 140, 82, and 394 days, respectively. Histology (poorly differentiated squamous cell) was found to be the only important factor in predicting response (P = .04) based on a multivariate analysis of nine pretreatment characteristics. The major dose-limiting toxicity was leukopenia. The incidences of nausea/vomiting, alopecia, and stomatitis/mucositis were 34%, 6%, and 3%, respectively. None were severe. Two patients had asymptomatic, moderate Alexander-grade cardiotoxicity. CONCLUSION: This study represents a large, controlled multicenter trial of single-agent mitoxantrone in the treatment of advanced NPC. Mitoxantrone was well tolerated and produced an overall response rate comparable to that of other single-agent therapies used in the treatment of advanced head and neck cancer. Combination trials with mitoxantrone for advanced disease should be considered.

Adult↗

PubMed1996

CEOP-IMVP-Dexa in the treatment of aggressive lymphomas: an Austrian multicenter trial.

PURPOSE: This trial evaluated the efficacy, toxicity, and practicability of a new intensive chemotherapy regimen in a multicenter setting of university and community hospitals. PATIENTS AND METHODS: We tested a hybrid protocol of two non-cross-resistant regimens, cyclophosphamide, epirubicin, vincristine, and prednisolone (CEOP) and ifosfamide, etoposide (VP-16), methotrexate, and dexamethasone (IMVP-Dexa) given every fourth week, three to six times according to response, in patients with untreated intermediate- and high-grade non-Hodgkin's lymphoma. Ten Austrian centers entered 81 patients onto this multicenter trial. Eleven patients were excluded. The median age was 55 years. Twenty-six of 70 patients had stage III or IV disease. The distribution among international risk categories low, intermediate-low, intermediate-high, and high was 20%, 34%, 23%, and 23%, respectively. RESULTS: Of 70 eligible patients, 56 (80%) had a complete remission and seven (10%) a partial remission. After a median observation time of 36 months, the estimated time to relapse and overall survival rates are 67% and 72%, respectively. Age and Karnofsky index were the only independent risk factors for survival. Toxicity was primarily hematologic, with a median granulocyte nadir of 0.56 x 10(9)/L. Sixty-seven percent of patients had infections; 25.7% were severe World Health Organization (WHO) grade III or IV. There were three treatment-related deaths. CONCLUSION: CEOP-IMVP-Dexa chemotherapy is safe and feasible on a groupwide basis even when used in community hospitals. Neutropenic infections are the major complications. A 72% 3-year survival rate in patients with intermediate- and high-grade non-Hodgkin's lymphoma warrants further studies. These data are the basis for a randomized trial to compare cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with CEOP/IMVP-Dexa.

Adolescent↗

PubMed2000

Activity of docetaxel in platinum-treated non-small-cell lung cancer: results of a phase II multicenter trial.

PURPOSE: Although several new chemotherapeutic agents are promising as primary therapy in non-small-cell lung cancer (NSCLC), few have demonstrated activity in platinum-refractory disease. Based on encouraging results reported in two single-institution studies of docetaxel in this setting, we performed a multicenter phase II trial evaluating this novel taxane in previously treated NSCLC patients prospectively categorized by platinum response status. PATIENTS AND METHODS: Eighty patients with NSCLC previously treated with platinum-based chemotherapy received docetaxel at a dose of 100 mg/m(2) intravenously over 1 hour, repeated every 21 days, accompanied by dexamethasone 8 mg orally twice daily for 5 days. Forty-seven patients (59%) were defined as platinum-refractory based on response status to prior therapy. RESULTS: The median number of cycles delivered per patient was four (range, one to 21 cycles). Partial response was observed in 13 (16%) of 80 of patients, with similar response rates in platinum-sensitive and platinum-refractory patients. The median survival time was 7 months, and the 1-year survival rate was 25%. Docetaxel was relatively well tolerated in this previously treated population. Grade IV neutropenia was common in patients (77%) but typically of brief duration. Febrile neutropenia was observed in 11 patients (14%), with no fatal infections. Severe fluid retention was rare (4% of patients). CONCLUSIONS: This multicenter phase II trial confirms antitumor activity and encouraging survival with docetaxel therapy in platinum-treated and platinum-refractory NSCLC. To validate these results, a phase III trial randomizing platinum-treated patients to docetaxel or best supportive care is underway.

Adult↗

PubMed2005

Sustained complete molecular remissions after treatment with imatinib-mesylate in patients with failure after allogeneic stem cell transplantation for chronic myelogenous leukemia: results of a prospective phase II open-label multicenter study.

PURPOSE: In the era of molecular therapy of chronic myelogenous leukemia (CML) applying BCR-ABL tyrosine kinase inhibitors, the usefulness of molecular end points, in particular, quantitative polymerase chain reaction (PCR) for BCR-ABL in monitoring responses has been broadly accepted. Therefore, we have designed a prospective phase II trial in CML, which, for the first time, evaluated the feasibility and safety of molecular end points as surrogate markers to guide through a stratified treatment algorithm within a multicenter trial. PATIENTS AND METHODS: As a clinical model, we adopted minimal residual disease (MRD) found in relapse after allogeneic stem cell transplantation (SCT) in CML. Forty-four patients were enrolled and received the BCR-ABL tyrosine kinase inhibitor imatinib (IM) at a starting dose of 400 mg/d. The quality of molecular responses achieved then decided on discontinuation of IM or dose escalation up to 800 mg/d, and finally, on application of donor lymphocyte infusions. Results Seventy percent of patients achieved a complete molecular response (CMR), defined as nested PCR-negativity for BCR-ABL in three consecutive samples. Interestingly, in four out of 10 patients who discontinued IM, CMR was durable even after cessation of IM with a median follow-up of 494 days. This suggests the possibility of long-term tumor control in a subset of patients. CONCLUSION: The treatment strategy showed that IM treatment was well-tolerated and highly efficacious in MRD after allogeneic SCT. Moreover, this study demonstrated that evaluation of a molecular end point within a multicenter trial can be a safe and effective tool for clinical decision making.

Adult↗