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Biomedical subjects

S W Langer

Publications and source records attributed to S W Langer.

18 recordsLinked to original sources
PubMed2006

Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies.

BACKGROUND: The purpose of this study was to assess the efficacy and tolerability of i.v. dexrazoxane [Savene (EU), Totect (US)] as acute antidote in biopsy-verified anthracycline extravasation. PATIENTS AND METHODS: Two prospective, open-label, single-arm, multicentre studies in patients with anthracycline extravasation were carried out. Patients with fluorescence-positive tissue biopsies were treated with a 3-day schedule of i.v. dexrazoxane (1000, 1000, and 500 mg/m(2)) starting no later than 6 h after the incident. Patients were assessed for efficacy (the possible need for surgical resection) and toxicity during the treatment period and regularly for the next 3 months. RESULTS: In 53 of 54 (98.2%) patients assessable for efficacy, the treatment prevented surgery-requiring necrosis. One patient (1.8%) required surgical debridement. Thirty-eight patients (71%) were able to continue their scheduled chemotherapy without postponement. Twenty-two patients (41%) experienced hospitalisation due to the extravasation. Mild pain (10 patients; 19%) and mild sensory disturbances (nine patients; 17%) were the most frequent sequelae. Haematologic toxicity was common as expected from the fact that the extravasation occurred during a chemotherapy course. Other toxic effects were transient elevation of alanine aminotransferases, nausea, and local pain at the dexrazoxane injection site. CONCLUSION: Dexrazoxane proved to be an effective and well-tolerated acute treatment with only one out of 54 assessable patients requiring surgical resection (1.8%).

Adult↗
PubMed2006

Randomized, double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy.

PURPOSE: To compare the antiemetic efficacy and tolerability of tropisetron plus metopimazine with tropisetron plus placebo during 4 cycles of multiple-day, cisplatin-based chemotherapy. MATERIALS AND METHODS: 82 chemotherapy-naive patients with germ cell cancer scheduled to 4 cycles of multiple-day cisplatin-based chemotherapy (20 or 40 mg/m(2)/day for 5 days) given every 3 weeks were included. A double-blind parallel trial design was used and patients randomized to tropisetron plus metopimazine or tropisetron plus placebo. Tropisetron was administered as a single 5 mg intravenous dose on days 1-5 and a single 5 mg oral dose on day 6, and metopimazine as 30 mg orally t.i.d. on day 1, and q.i.d on days 2-6. RESULTS: Patients were evaluable for efficacy during a total of 195 cycles. Small, but certain advantages were obtained with the combination. In cycle 1, complete protection from emetic episodes on day 1, days 1-5, days 6-9 and days 1-9 was achieved in 85.7%, 42.9%, 86.2% and 40.5% with tropisetron plus metopimazine and in 90.0%, 22.5%, 64.3% and 17.5% with tropisetron plus placebo, respectively. This difference achieved statistical significance in the overall period, days 1-9 (P = 0.029). During the entire period (days 1-9), significantly less nausea was seen in patients receiving tropisetron plus metopimazine (P = 0.027), whereas other nausea parameters did not reach statistical significance. The cumulative emetic protection rate after 4 cycles was 0.51 with tropisetron plus metopimazine and 0.25 with tropisetron plus placebo (P = 0.037). Side effects were generally few and mild with both treatments and no significant differences were seen. CONCLUSION: Tropisetron plus metopimazine is superior to tropisetron during 4 cycles of multiple-day cisplatin-based chemotherapy, but both treatments are ineffective in a number of patients. The effect of the combination seems comparable to that of ondansetron plus dexamethasone. Newer drugs such as the neurokinin(1) receptor antagonist, aprepitant, should be investigated to optimize antiemetic therapy in patients receiving multiple-day chemotherapy.

Adolescent↗
PubMed2006

A prospective study of PET/CT in initial staging of small-cell lung cancer: comparison with CT, bone scintigraphy and bone marrow analysis.

BACKGROUND: Small-cell lung cancer (SCLC) accounts for 15%-20% of all lung cancer cases. Accurate and fast staging is mandatory when choosing treatment, but current staging procedures are time consuming and lack sensitivity. PATIENTS AND METHODS: A prospective study was designed to examine the role of combined positron emission tomography/computed tomography (PET/CT) compared with standard staging (CT, bone scintigraphy and immunocytochemical assessment of bone marrow biopsy) of patients with SCLC. Thirty-four consecutive patients were included. Twenty-nine patients received initial PET/CT. RESULTS: PET/CT caused change of stage in 5/29 (17%). Excluding patients with unconfirmed findings or pleural effusion, the sensitivity for accurate staging of patients with extensive disease was the following: for standard staging 79%, PET 93% and PET/CT 93%. Specificity was 100%, 83% and 100%, respectively. CONCLUSION: The results from this first study on PET/CT in SCLC indicates that PET/CT can simplify and perhaps even improve the accuracy of the current staging procedure in SCLC. A larger clinical trial, preferably with consequent histological confirmation in case of discordance, however, is warranted.

Aged↗
PubMed2001

Dexrazoxane is a potent and specific inhibitor of anthracycline induced subcutaneous lesions in mice.

BACKGROUND: Recently, we have shown that dexrazoxane (ICRF-187) is an effective antidote against accidental extravasation of anthracyclines. Thus, it inhibits the lesions induced by subcutaneous (s.c.) daunorubicin, idarubicin, and doxorubicin in mice and has proven to be successful clinically as well. Dexrazoxane is a potent metal ion chelator as well as being a catalytic inhibitor of DNA topoisomerase II. However, the mechanism behind the protection against anthracycline extravasation is not known. MATERIALS AND METHODS: Mice were injected s.c. with daunorubicin or doxorubicin. Systemic N-acetylcysteine, alfa-tocoferol, amifostine, merbarone, aclarubicin, ADR-925, and EDTA were administered i.p. immediately hereafter or as a triple-treatment over six hours. Intralesional (i.l.) adjuvants were injected immediately after and into the same area as the anthracycline. The frequency, duration, and sizes of wounds were observed until complete healing of all wounds. RESULTS: Triple-treatment with systemic dexrazoxane was superior to single dosage and completely prevented lesions after s.c. daunorubicin and doxorubicin. Low-dose i.l. dexrazoxane was effective in protecting as well. In contrast, none of the other seven adjuvants was effective. Protection was not achieved with local cooling, however, topical ice did not impair the efficacy of dexrazoxane. CONCLUSIONS: Dexrazoxane is extremely effective and apparently quite specific in protecting against lesions after s.c. doxorubicin and daunorubicin.

Animals↗
PubMed2000

Treatment of anthracycline extravasation with dexrazoxane.

Accidental extravasation of anthracyclines is a feared complication. Present treatment consists of local cooling and extensive surgical debridement, which often results in severe morbidity. All clinically important anthracyclines are topoisomerase II poisons that are antagonized by topoisomerase II catalytic inhibitors such as dexrazoxane. Therefore, we investigated whether dexrazoxane protects against extravasation lesions caused by anthracyclines. B6D2F1 mice received s.c. daunorubicin, doxorubicin, or idarubicin followed by systemic treatment with dexrazoxane or saline. One single systemic dose of dexrazoxane immediately after s.c. administration of doxorubicin, daunorubicin, or idarubicin reduced the tissue lesions (expressed as area under the curve of wound size times duration) by 96% (P < 0.0001), 70% (P < 0.0001), and 87% (P = 0.0004), respectively. Moreover, the treatment resulted in a statistically significant reduction in the fraction of mice with wounds as well as the duration of wounds. The induction of wounds was dose-dependent, as was the degree of protection by dexrazoxane. Dexrazoxane could be administered up to 3 h after the anthracycline without loss of protection. Triple-dosage of dexrazoxane tended to be more effective than a single injection. Dexrazoxane had no effect on lesions induced by hydrogen peroxide. This is the first report of use of a topoisomerase II catalytic inhibitor such as dexrazoxane in the treatment of anthracycline extravasation injuries. These convincing preclinical data represent a novel nontoxic approach that can easily be implemented into the clinical handling of accidental extravasation of anthracyclines.

Animals↗
PubMed1999

Granisetron compared with prednisolone plus metopimazine as anti-emetic prophylaxis during multiple cycles of moderately emetogenic chemotherapy.

This randomized, double-blind, double-dummy parallel study compared the anti-emetic efficacy and tolerability of the serotonin antagonist granisetron with prednisolone plus the dopamine D2 antagonist metopimazine during nine cycles of moderately emetogenic chemotherapy. Chemotherapy naive women with stage I or II breast cancer scheduled to intravenous cyclophosphamide, fluorouracil and methotrexate or cyclophosphamide, epirubicin and fluorouracil every 3 weeks were included. Patients received a single intravenous dose of granisetron 3 mg or a 3-day oral treatment with prednisolone 25 mg once a day plus metopimazine 30 mg four times a day. A total of 223 women were enrolled and 218 patients (97.8%) were evaluable for efficacy. Granisetron (n = 109) was superior to prednisolone plus metopimazine (n = 109) in the prophylaxis of acute nausea and vomiting during the first cycle of chemotherapy (P < 0.001) and prednisolone plus metopimazine was superior on days 2-5 (P = 0.002). Overall, granisetron was superior on days 1-5 (P = 0.009). The median number of cycles completed with granisetron was five (95% confidence interval 4-6) compared with two (95% confidence interval 2-2) for prednisolone plus metopimazine (P = 0.0019). Constipation and rash were reported more frequently with granisetron (P < 0.001 and P = 0.043 respectively) and palpitations more frequently with prednisolone plus metopimazine (P = 0.015). In conclusion, the number of cycles completed with granisetron was significantly higher than the number completed with prednisolone plus metopimazine, but the anti-emetic efficacy of both treatments declined during multiple cycles of moderately emetogenic chemotherapy.

Adult↗
PubMed1999

Inhibitors of topoisomerase II as pH-dependent modulators of etoposide-mediated cytotoxicity.

Chloroquine intercalates into DNA and protects cells against topoisomerase II (topo II) poisons such as etoposide by hindering the DNA cleavage reaction of this target enzyme. Chloroquine, in contrast to etoposide, is a weak base and therefore barely enters the cell when the extracellular fluid is acidic, as is the case in most solid tumors. Such a pH-dependent drug interaction could be useful in targeting the cytotoxicity of topo II poisons toward solid tumors. Unfortunately, antagonistic chloroquine concentrations cannot be reached in vivo because of its unacceptable toxicity. Thus, antagonists with a higher therapeutic index are needed. We report here on the structure-activity relationship of several chloroquine and acridine analogues in a clonogenic assay. There were major differences in the cytotoxicity of the different compounds, with acridines being 50-fold more toxic than the chloroquine analogues. Several compounds were, however, able to antagonize etoposide-mediated cytotoxicity in a pH-dependent manner as chloroquine. Dependency on pH was lost if the aminoalkyl side arm of chloroquine was removed or lengthened by one CH2 whereas pH dependency was strong with hydroxychloroquine. In contrast, the aminoalkyl side arm was clearly dispensable in the acridines because both quinacrine and 9-aminoacridine demonstrated profound pH dependency. The results from clonogenic assay were compared with cellular transport measurements and topo II enzyme inhibition. Compounds with the most marked pH-dependent intracellular accumulation were also the best pH-dependent protectors of etoposide cytotoxicity, clearly supporting the hypothesis that extracellular pH can be used to regulate topo II poisoning.

Antineoplastic Agents, Phytogenic↗
PubMed1996

[Male breast cancer. A review].

Male breast cancer is a rare disease, making up less than 1% of all breast cancers. A review of the literature does not disclose major differences between male and female breast cancer regarding etiological, prognostic or diagnostic features. In male breast cancer endocrine therapy is more widely used, but there are otherwise no differences in the therapeutic strategies used.

Breast Neoplasms, Male↗
PubMed1996

Brain relapses in chemotherapy-treated small cell lung cancer: a retrospective review of two time-dose regimens of therapeutic brain irradiation.

The incidence of brain metastases secondary to small cell lung cancer (SCLC) is about 35% and the treatment strategy of brain irradiation with respect to dose and fractionation is controversial. In order to evaluate treatment outcome of brain irradiation in SCLC patients with brain relapse, we retrospectively evaluated all patients treated with brain irradiation in the eastern part of Denmark from 1988 to 1992 (PCI patients excluded). During this 5-year period, 101 evaluable patients were included (44 females, 57 males) (median age 61 years; range, 39-75 years). Forty-four patients, of whom 43 were in extracerebral complete remission (CR), received extended course (EC) brain irradiation (> 45 Gy, treatment schedule > 4 weeks). Fifty-seven patients received short course (SC) brain irradiation (< 30 Gy, treatment schedule < 1 week). Among the SC treated patients, 14 were in CR, 20 had partial remission or stable disease and 23 had progressive extracerebral disease. The median survival (from diagnosis of brain metastases) in the group receiving irradiation with EC (44 patients) was 160 days (range, 74-2021 days), while the 57 patients treated with SC had a median survival of 88 days (range, 20-948 days) (P = 0.00001, Log-Rank analysis). In a subgroup of 14 patients in extracerebral CR, receiving SC irradiation, the median survival was 83 days (range, 15-948 days). When the latter patients were compared to the 43 patients in CR in the group treated with EC, a statistically significant difference was shown (P = 0.034, Log-Rank analysis). Using Cox-hazard regression analysis with backward elimination, liver metastases and poor performance status were adverse prognostic signs, although the only significant parameters of survival were gender (female vs. male, relative risk of dying 1 and 1.52, P = 0.05) and schedule of brain irradiation (extended course vs. short course, relative risk of dying, 0.36 and 1, P < 0.001). Extended course irradiation of brain relapse secondary to SCLC seems in general to be of limited value, although a significant prolonged survival at approximately 7 weeks, was obtained. The prolongation of survival does not seem worthwhile considering the length of treatment time (5-6 weeks) compared to SC treatment (1 week). However, the data do not permit evaluation of the quality of life of the patients. This retrospective evaluation suggests the need for randomized trials with carefully planned quality-of-life assessments.

Adult↗
PubMed1995

[Long-term prognosis of pulmonary sarcoidosis. 2. Cardiac sarcoidosis and other extrapulmonary manifestations].

Frequency and prognostic importance of extrapulmonary manifestations have been examined in 254 patients with intrathoracic sarcoidosis. A follow-up was carried out after a median of 27 years from diagnosis. All patients could be traced. Extrapulmonary manifestations were found in 119 patients (47%), mostly occurring within the first years after diagnosis of intrathoracic sarcoidosis; skin manifestations were most frequently seen. ECG-abnormalities were found in 35 patients (14%); in 17 cases in the form of sinus tachycardia. No excess mortality was found (80 deaths observed versus 66 expected). The causes of death were related to sarcoidosis in 41%. Only tachycardia was associated with an unfavourable prognosis and this association vanished after adjusting for decreased lung function. None of the other extrapulmonary manifestations were associated with an unfavourable vital prognosis. Erythema nodosum was of no prognostic significance concerning survival. In conclusion, extrapulmonary manifestations are frequent in patients with intrathoracic sarcoidosis but do not influence vital prognosis.

Aged↗
PubMed1995

Electrocardiographic changes in patients with intrathoracic sarcoidosis: influence on prognosis.

A retrospective evaluation of 244 electrocardiograms obtained at rest at time of diagnosis from a population of 254 patients with intrathoracic sarcoidosis was carried out. Thirty-five (14%) were abnormal. Sinus tachycardia was present in 17 (7%), the rest encompassing various degrees of right-sided bundle branch, atrioventricular first degree block, ventricular extrasystolia and ST-depression. At follow-up after a median time of 27 years we found a significantly higher mortality risk in the group with ECG-changes compared to those without. Excess mortality was increased when comparing patients with tachycardia to those without. However, when adjusted for FEV1, the risk of death was not significantly different between the two groups.

Adolescent↗
PubMed1994

Asbestos-induced lung injury among Danish jewelry workers.

Asbestos has been used extensively in a variety of occupations. In the jewelry industry, inadequate hygiene practices may often go unrecognized with resultant exposure to hazardous amounts of asbestos. We report on four retired jewelers. Two of these had both pleural and parenchymal changes. One had isolated pleural plaques and the final patient showed only parenchymal infiltrates. Their work involved hand cutting asbestos plates used for protection during soldering. In the soldering process asbestos fibers were then blown into the workroom air as the plates broke down. In addition, at the end of each work day the workroom floor was swept, with subsequent airborne asbestos dust distribution. Any patient with pleural plaques or interstitial lung disease should be questioned about potential sources of asbestos exposure in the past, regardless of present employment status.

Aged↗
PubMed1993

[The value of bone marrow scintigraphy in patients with recurrent breast cancer].

Attempts were made to assess the value of various methods of demonstration of bone metastases in patients with recurrence of cancer of the breast. A material of 123 patients with suspected or verified recurrence of cancer of the breast was submitted to a programme of investigation consisting of conventional X-ray survey of the axial skeleton and thorax, bone tissue scintigraphy, bone marrow scintigraphy, bone biopsy and aspiration of marrow and blood status including serum alkaline phosphatase. 54% and 29% of the patients had bone, metastases as assessed radiographically and by biopsy, respectively. In patients with radiographically demonstrated bone metastases, the predictive value of positive (PV-pos) whole-body scintigraphy was 79%. The findings on bone tissue scintigraphy and bone marrow scintigraphy were in agreement with the radiographic findings in 78% and 72%, respectively, and with the biopsy findings in 71% and 74%, respectively, of the cases. All of the cases of metastases verified by biopsy were identified also by radiographic examination and by bone tissue scintigraphy. The predictive value of negative bone tissue scintigraphy (PV-neg) was 76% and of bone marrow scintigraphy 65%. With biopsy as the final proof, bone tissue scintigraphy, bone marrow scintigraphy and radiography were found to have PV-pos values of 96%, 89% and 95%, respectively and PV-neg values of approximately 50% for all three forms of examination. Bone marrow scintigraphy has thus no diagnostic advantages as compared with bone tissue scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow↗