Biomedical subjects

L Roman

Publications and source records attributed to L Roman.

At least 19 recordsLinked to original sources

PubMed2001

Treatment of patients with ovarian carcinoma with pegylated liposomal doxorubicin: analysis of toxicities and predictors of outcome.

BACKGROUND: Pegylated liposomal doxorubicin is a new formulation with activity against epithelial ovarian carcinoma (EOC). The authors sought to determine patient characteristics that may predict for response to this treatment and favorable time to failure as well as survival. METHODS: Eight patients in a Phase I study and 44 patients in two consecutive Phase II studies who were treated with pegylated liposomal doxorubicin (40-60 mg/m2 every 3 weeks for the first two cycles and 40 mg/m2 every 4 weeks thereafter) after failing initial platinum-based chemotherapies for ovarian carcinoma were analyzed. Associations were sought for response, time to failure (TTF), and survival after the treatment and various pretreatment characteristics. RESULTS: Treatment with pegylated liposomal doxorubicin yielded 23% objective responses in measurable disease and 31% overall responses, including serum CA 125-defined responses. The median TTF was 5.2 months (95% confidence interval, 4.1-6.9 months) in all patients, and the median response duration in all responders was 13.2 months (95% confidence interval, 11.9-18.5 months). The overall median survival was 15 months (95% confidence interval, 11-40 months). The main predictive factors were tumor size and baseline hemoglobin level for TTF, and these plus Karnofsky performance status were the main predictive factors for survival. CONCLUSIONS: Pegylated liposomal doxorubicin is an effective drug when it is given as secondary therapy to patients with EOC. Lack of bulky disease is the major predictor for a favorable response, TTF, and survival. The role of this treatment in combination with other effective drugs should be explored in both previously treated and untreated patients with ovarian carcinoma.

Adult↗

PubMed2001

Titration of low K(d) binding sites: binding of arginine analogs to nitric oxide synthases.

Spectrophotometrically monitored ligand titration is an important method for the determination of equilibrium dissociation constants (K(d)) from nitric oxide synthases (NOS). Low K(d) sites such as the tetrahydrobiopterin and arginine binding sites present difficulties in that experiments often require enzyme concentrations of the same magnitude as the K(d). An analytical method based on computer simulation is described that allows the estimation of K(d) values without an independent means of monitoring free ligand or without an accurate prior determination of the number of binding sites. The K(d) for arginine is approximately 0.5 microM for the tetrahydrobiopterin replete neuronal and inducible isoforms (nNOS and iNOS), while the endothelial isoform has a slightly higher K(d) (1.5 microM). N-OH-arginine (an intermediate) binds to nNOS with a K(d) of around 0.2 microM, while the inhibitors N-methyl-arginine and N-nitro-arginine bind more tightly; our best K(d) estimates are 100 nM or lower.

Animals↗

PubMed2001

Essential oils analysis. II. Mass spectra identification of terpene and phenylpropane derivatives.

Mass spectra are widely used in order to identify the peaks resulting from a chromatographic separation. The most common approach to solve the problem for unknowns on whom very little other structural information is available is the use of a retrieval algorithm and a reference mass spectra database. The wide variety of mass spectra recorded with different instruments under various experimental conditions can lead to erroneous results. In order to improve the accuracy of the results, we proposed earlier an identification algorithm, which combines the information obtained from both GC and MS fingerprints. This paper presents a new algorithm based on the comparison of the unknown mass spectra with several libraries (including Wiley and NIST) by using reverse and direct search algorithms respectively. The results of the comparisons were quantified with respect to the match quality and the interference compounds. A global match index for the comparison using all the above information was computed and the results were presented as the match probability. This index expresses more accurately the matches between unknown and all the available libraries mass spectra. In order to verify our algorithm, we tried to identify the compounds separated by GC-MSD from different species of Acorus calamus L. (Araceae) essential oils. The probability of the matches increases compared with the quality of matches resulting from Wiley and NIST libraries.

Algorithms↗

PubMed2001

Development of a time-cycled volume-controlled pressure-limited respirator and lung mechanics system for total liquid ventilation.

Total liquid ventilation can support gas exchange in animal models of lung injury. Clinical application awaits further technical improvements and performance verification. Our aim was to develop a liquid ventilator, able to deliver accurate tidal volumes, and a computerized system for measuring lung mechanics. The computer-assisted, piston-driven respirator controlled ventilatory parameters that were displayed and modified on a real-time basis. Pressure and temperature transducers along with a lineal displacement controller provided the necessary signals to calculate lung mechanics. Ten newborn lambs (<6 days old) with respiratory failure induced by lung lavage, were monitored using the system. Electromechanical, hydraulic, and data acquisition/analysis components of the ventilator were developed and tested in animals with respiratory failure. All pulmonary signals were collected synchronized in time, displayed in real-time, and archived on digital media. The total mean error (due to transducers, analog-to-digital conversion, amplifiers, etc.) was less than 5% compared with calibrated signals. Components (tubing, pistons, etc.) in contact with exchange fluids were developed so that they could be readily switched, a feature that will be important in clinical settings. Improvements in gas exchange and lung mechanics were observed during liquid ventilation, without impairment of cardiovascular profiles. The total liquid ventilator maintained accurate control of tidal volumes and the sequencing of inspiration/expiration. The computerized system demonstrated its ability to monitor in vivo lung mechanics, providing valuable data for early decision making.

Analysis of Variance↗

PubMed2000

Determination of cadmium by differential pulse adsorptive stripping voltammetry.

A study of the adsorptive stripping voltammetry of cadmium on a mercury drop electrode is reported in which 2-mercapto-5-phenyl-amino-1,3,4-thiadiazole (MPATD), synthesized at home has been used as a chelating agent. The most suitable operating conditions and parameters such as buffer, pH, deposition potential, deposition time, ligand concentration, scan rate and others were selected and the determination of cadmium from aqueous solutions using the standard additions method was possible. As validation criteria, the linearity and range, repeatability of the signal, repeatability of the concentration and accuracy were investigated. A limit of detection of 4.67 x 10(-10) M and a limit of quantification of 1.55 x 10(-9) M were achieved. The interference of other metals and organic substances was studied. Concerning a possible catalytic effect, no one was found. The method was designed in order to determine Cd from biological samples.

Cadmium↗

PubMed2000

Phase II study of liposomal doxorubicin in advanced gynecologic cancers.

OBJECTIVE: Pegylated liposomal doxorubicin (Doxil) may have enhanced therapeutic efficacy and reduced toxicity compared with the parent compound. This phase II study further evaluates the activity of Doxil in patients with ovarian cancer and explores activity in other gynecologic cancers. METHODS: Sixty-three patients were treated with Doxil 50 mg/m(2) infused over 1 h; 44 were evaluable. Forty-eight had epithelial ovarian cancer and all received prior treatment with cisplatin and paclitaxel: 27 received two to six prior regimens, 44 were platinum resistant, 21 patients had measurable disease, and 27 had evaluable disease only. RESULTS: The overall survival of these patients was 10 months (range, 0.25-33); progression-free survival was 3 months (range, 0.25-18). The response rate among those with measurable disease was 19%, with a median duration of 4.5 months (range, 3-12). The response rate of 22 patients with elevated CA-125 was 59%; median duration was 3.5 months (range, 1-12). Also, 27% achieved prolonged stabilization of disease for a median of 7 months (range, 5-18). Overall, treatment was well tolerated in this heavily pretreated population. Grade 3 and 4 toxic effects were: 5 grade 3 stomatitis, 3 grade 3 skin, 1 each grade 4 neutropenia and thrombocytopenia, 5 admits for infection, and no neutropenic fever; nausea and vomiting were uncommon in 204 cycles to ovarian cancer patients. CONCLUSION: This study demonstrates the activity of Doxil in heavily pretreated patients with ovarian cancer and poor prognostic features and confirms the prolonged responses and favorable toxicity profile. Encouraging findings were also observed in the patients with nonovarian gynecologic cancers.

Adult↗

PubMed2000

Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.

BACKGROUND & AIMS: One-year lamivudine therapy significantly suppressed hepatitis B virus (HBV) replication, improved hepatic necroinflammatory activity, and prevented progression of fibrosis. However, the effects of prolonged therapy are unknown. METHODS: A total of 334 Asian patients with chronic hepatitis B from a previously reported 1-year study were randomized to receive either lamivudine (100 or 25 mg) or placebo for another year. The effects of treatment on serum HBV-DNA suppression, alanine transaminase (ALT) normalization, and hepatitis B e antigen (HBeAg) seroconversion were measured. The presence of YMDD variant HBV and its effect were also determined. RESULTS: A significantly greater proportion of patients achieved sustained HBV-DNA suppression and ALT normalization with 100 mg lamivudine daily for 2 years compared with lamivudine for 1 year followed by placebo for the second year (P<0.001). Daily lamivudine therapy for 2 years was safe and resulted in incremental HBeAg seroconversion from 17% at week 52 to 27% at week 104. HBeAg seroconversion during continued lamivudine therapy increased linearly with increasing pretherapy ALT levels (P< 0.001). Despite the emergence of YMDD mutant in 38% of the patients, they continued to clear serum HBeAg and maintain lower median serum HBV-DNA and ALT levels than baseline values. In contrast, ALT levels increased 8-12 weeks after switching from lamivudine to placebo, but returned to normal once lamivudine treatment was resumed. CONCLUSIONS: Treatment with lamivudine for 2 years is both well tolerated and efficacious in patients with chronic hepatitis B.

Adult↗

PubMed2000

A phase I trial of a human papillomavirus (HPV) peptide vaccine for women with high-grade cervical and vulvar intraepithelial neoplasia who are HPV 16 positive.

Eighteen women with high-grade cervical or vulvar intraepithelial neoplasia who were positive for human papillomavirus (HPV) 16 and were HLA-A2 positive were treated with escalating doses of a vaccine consisting of a 9-amino acid peptide from amino acids 12-20 encoded by the E7 gene emulsified with incomplete Freund's adjuvant. Starting with the eleventh patient, an 8-amino acid peptide 86-93 linked to a helper T-cell epitope peptide with a covalently linked lipid tail was added. Patients with colposcopically and biopsy-proven cervical intraepithelial neoplasia/vulvar intraepithelial neoplasia II/III received four immunizations of increasing doses of the vaccine each 3 weeks apart, followed by a repeat colposcopy and definitive removal of dysplastic tissue 3 weeks after the fourth immunization. Patients were skin tested with the E7 12-20 peptide as well as control candida, mumps, and saline prior to and after the series of immunizations. Peripheral blood mononuclear cells were obtained by leucopheresis prior to and after the series of immunizations for analyses of CTL reactivity to the E7 12-20 and 86-93 epitope sequences. The presence of HPV 16 was assessed by DNA PCR on cervical scrapings and the biopsy specimens after vaccination. Pathology specimens were analyzed before and after vaccination for the presence of dysplasia, and the intralesional infiltrate of CD4/CD8 T-cells and dendritic cells was measured by immunohistochemical staining. Only 3 of 18 patients cleared their dysplasia after vaccine, but an increased S100+ dendritic cell infiltrate was observed in 6 of 6 patients tested. Cytokine release and cytolysis assays to measure E7-specific reactivity revealed increases in 10 of 16 patients tested. No positive delayed type hypersensitivity skin test reactivity was shown in any patient to HPV E7 12-20 before or after vaccinations. Virological assays showed that 12 of 18 patients cleared the virus from cervical scrapings by the fourth vaccine injection, but all biopsy samples were still positive by in situ RNA hybridization after vaccination. Six patients had partial colposcopically measured regression of their cervical intraepithelial neoplastic lesions in addition to the three complete responders. The data establish that a HPV-16 peptide vaccine may have important biological and clinical effects and suggest that future refinements of an HPV vaccine strategy to boost antigen-specific immunity should be explored.

Adult↗

PubMed1999

[High-frequency oscillatory ventilation as salvage strategy in the newborn infant. Spanish multicenter study. I].

OBJECTIVE: The aim of this study was to evaluate the results of high frequency ventilation (HFV) used as a rescue strategy in newborn infants with severe lung disease who either failed conventional mechanical ventilation (CMV) or had an air block. PATIENTS AND METHODS: From April 1995 to June 1998, 241 infants with severe lung disease and managed according to a common protocol of HFV used as a rescue strategy were prospectively evaluated in the nine participating level III Spanish Neonatal Intensive Care Units. The most frequent diagnoses were respiratory distress syndrome (119), meconium aspiration (24), pneumonia (19) and congenital diaphragm hernia (18). RESULTS: Mean +/- SD gestational age and birth weight were 32.0 +/- 5.5 weeks and 1,187 +/- 1,071 g, respectively. All babies were previously manages with CMV for a mean of 59 hours. HFV was started at a mean postnatal age of 82 hrs, with a mean oxygenation index (OI) of 28.3 +/- 15.3 and an a/A DO2 of 0.10 +/- 0.08. Initial mean HFV settings were: mean airway pressure 12.8 +/- 3.4 mbar, frequency 8.3 +/- 1.4 Hz, amplitude 53 +/- 20 percent, tidal volume 2.2 +/- 0.7 ml/kg and FiO2 0.88 +/- 0.2. At two hours of HFV there was a significant increase in the mean PaO2 (from 48 to 80 mmHg), with a concomitant decrease in FiO2 (from 0.88 to 0.79), PaCO2 (from 60 to 46 mmHg) and OI (from 28 to 18). Mean a/A DO2 increased from 0.10 to 0.19; these changes remained similar thereafter. HFV was suspended after a mean of 95 hrs because of improvement in 70%, death in 19% and failure to improve the clinical condition in the remaining 19%. Intrahospital death rate was 32%. The following complications were observed: pneumothorax (10%), interstitial emphysema (4%), intraventricular hemorrhage grades III and IV (14.5%) and bronchopulmonary dysplasia (35%). CONCLUSIONS: HFV is an effective rescue strategy that improves pulmonary gas exchange within two hours of its initiation.

Female↗

PubMed1999

Worse six-month outcome for patients with multiple stents in a single coronary artery.

BACKGROUND: Before the "era" of optimal stent deployment, very few data concerning multiple stents in a single coronary artery showed restenosis rates up to 60%. OBJECTIVE: To evaluate the 6-month outcome of patients receiving multiple Palmaz-Schatz stents (> or =2 stents) in a single coronary artery compared to those receiving single stents. METHODS: Three hundred and forty-eight patients having multiple stents were compared to 174 patients receiving single stents during a 6-month follow-up. RESULTS: Repeat target lesion revascularization (RTLR), either repeat PTCA or CABG, was 10.4% in the single-stent group, 22.6% in the two-stent group, and 23.1% in the > or =2 stent group (p = 0.001, single versus 2 or > or =2 stents). There was not a significant difference between single stent and multiple stent groups in myocardial infarction and death during 6-month follow-up. Multivariate analysis showed multiple stents, diabetes mellitus, and type C lesion to be predictors of RTLR. CONCLUSIONS: Placement of two or more stents was associated with a significantly higher RTLR compared with single stent placement. The optimal approach to diffuse coronary artery disease remains to be defined.

Aged↗

PubMed1998

The voltammetric study of 2-mercapto-5-phenylammino-1,3,4-thiadiazole using carbon paste electrodes.

A rapid and accurate voltammetric method for the quantitative determination of 2-mercapto-5-phenylammino-1,3,4-thiadiazole (MPATD) with carbon paste electrodes (CPE) has been developed. The study was made by cyclic voltammetry between -0.4 and +0.6 V with 50 mV s(-1) sweep rate in aqueous solution. After successive oxidation/reduction cycles we found a total oxidation of MPATD at +0.45 V. As the compound is oxidated, the reduction current peak increases at +0.13 V, indicating an irreversible process. Following only the oxidation process in the -0.1 to +0.6 V range, we investigated the optimum scan rates at different current densities and pH values (realised with buffers, pH between 1.0 and 10.0) with CPE versus Ag/AgCl reference electrode using linear sweep voltammetry. We found a good linear relation between the current peak height and concentration in a 2.5 x 10(-9)-1.25 x 10(-7) mol ml(-1). This method allows the quantitative detection of the MPATD as it or from dosage forms and biological media.

Chemistry Techniques, Analytical↗

PubMed1998

Conductometric method for the quantitative analysis of Pb(II) and Cd(II) with 2-mercapto-5-R-amino-1, 3, 4-thiadiazole derivatives.

The reactions of the cations with 2-mercapto-5-R-amino-1,3,4-thiadiazole derivatives were studied conductometrically with the purpose of establishing a new conductometric method for the quantitative analysis of Pb(II) and Cd(II). Aqueous solutions of Pb(NO3)2 and Cd(CH3COO)2 were titrated with hidroalcoholic solutions of 2-mercapto-5-amino-1,3,4-thiadiazole (MATD), 2-mercapto-5-allylamino-1,3,4-thiadiazole (MA1ATD) and 2-mercapto-5-acetylamino-1,3,4-thiadiazole (MAcATD) and 2-mercapto-5-phenilamino-1,3,4-thiadiazole (MFATD) in different concentrations. The reactions takes place at pH 6.5 (realised with acetate buffer). A linear classical titration curves was obtained. In solutions more concentrated than 10(-2) M just one equivalence point can be noticed, corresponding to 1:2 Me:R stoechiometries. For concentration less than 10(-2) M two equivalence point were observed at 1:1 and 2:1 ratio of Me:R, indicating the step formation of the complex. Accurate conductometric determinations can be made using the second break points of the titration curves as equivalence points. The amounts of Cd(II) and Pb(II) taken and recovered are good, with an error less than 1%.

Cadmium↗

PubMed1998

The potentiometric and spectrophotometric determination of dissociation constants for same 2-mercapto-5-R-amino-1,3,4-thiadiazole derivatives.

In order to establish the dissociation constants of organic compounds, the spectrophotometric and potentiometric methods are the most precise and useful ones. Comparing the results, we used both methods for three derivatives of 2-mercapto-5-R-amino-1,3,4-thiadiazole. For the pKa determination by the spectrophotometric method we measured the ratio between the concentration of dissociated and undissociated forms. The ratio was calculated from spectral data. The potentiometric method for pKa consists of measuring the pH values within a potentiometric titration with 0.1 M NaOH. The results proved a very low acid character of the derivatives. The pKa values were influenced by the properties of the amino group substituents, and the results confirm the theoretical considerations. The study confirms the thion-thiolic tautometry of the 2-mercapto-5-R-amino-1,3,4-thiadiazole derivates and their property of being ligands for the coordination of the cations of some representative and transitional metals, with application in the preconcentration, in the detection and the quantitative determination of polluting and toxic cations in environmental analysis.

Cations↗

PubMed1998

Comparison of GC-MS and TLC techniques for asarone isomers determination.

Two chromatographic methods (GC-MS and TLC) have been developed for separation and determination of alpha and beta asarone from essential oils and alcoholic extracts. The study has been performed on the Acorus calamus (I) and Asarum europaeum (II) essential oils of Romanian origin and the alcoholic extract of Acorus calcamus L (III) and it is a consequence of the International Boards exigency regarding the presence of beta asarone in food, beverages and pharmaceuticals. The isomers were determined using both internal and external standard methods. Both SIM and SCAN techniques were used and the results were compared regarding the chromatographic resolution and interference compounds. The method exhibits good repeatability and low detection limit but is expensive and time consuming. The two isomers concentrations are 5.2- 6.7 microg ml(-1) (I), 460-510 microg ml(-1) (II) and 2.7 5.7 microg ml (III) for alpha asarone and 91-98 microg ml(-1) (I), 24-29 microg ml(-1) (II) and 88 97 microg ml(-1) (III) for beta asarone. The TLC method was developed as an alternative for the GC method. The separation was performed on silica gel plates using toluene: ethyl acetate 8:2 as mobile phase. The evaluation of the chromatograms was made by densitometry using multiple wavelength. The sum of the two isomers are between 80-120 microg ml(-1) (I) and 127-145 microg ml(-1) (III) using spectrophotometric detection and between 73-93 microg ml(-1) (I) and 99-105 microg ml(-1) (III) using fluorimetric detection. The results of the two chromatographic methods were compared. Even the GC is more sensitive, mathematical computations for spots optimization and interference elimination could improves the TLC quality results.

Allylbenzene Derivatives↗

PubMed1998

Electrochemical study of some 2-mercapto-5-R-ammino-1,3,4-thiadiazole derivatives using carbon paste electrodes.

The electrochemical study of some 2-mercapto-5-R-ammino-1,3,4-thiadiazole derivatives was made by cyclic and linear sweep voltammetry using a carbon paste electrode (CPE, graphite/solid paraffin ratio 2:1) as working electrode and an Ag/AgCl reference electrode. The current-potential curves were recorded in anodic polarisation in -0.1 and +1.3 V range using aqueous solutions and different buffers (between pH 1.2 and 10.0), with 20 or 50 mV s(-1) sweep rate. The oxidation peak appears between +0.65 and +0.70 V due to disulphides formation. The 5-phenyl derivative has two oxidation peaks, the first at +0.45 +/- 0.03 V and the second at +0.65 +/- 0.03 V. The oxidation potentials are pH dependent, decreasing from 0.9 +/- 0.1 V at pH 1.2 to 0.6 +/- 0.1 V at a pH between 8.0 and 10.0. In some potential ranges depending on pKa of molecules the oxidation potential and oxidation current are pH independent. Simple, precise and accurate voltammetric methods for the determination of these compounds were developed and validated in 2.5 x 10(-6)-7.5 x 10(-4) mol l(-1) concentration ranges. The detection limits were 2.3 micromol l(-1) for 5-ammino-, 12.3 micromol l(-1) for 5-acetylammino-, 11.6 micromol l(-1) for 5-allylammino-, and 1.2 micromol l(-1) for 5-phenylammino-2-mercapto-1,3,4 thiadiazole derivatives.

Electrochemistry↗

PubMed1998

Essential oils analysis. I. Evaluation of essential oils composition using both GC and MS fingerprints.

The chemical nature of essential oils makes them suitable for analysis using a gas chromatography-mass selective detector (GC-MSD). Mass spectra (MS) libraries can not be used as unique and absolute criteria for the identification of chromatogram peaks. The wide variety of MS of the libraries, recorded in different conditions, can lead us to erroneous results. In order to increase the reliability of the analytical results, we used as identity criteria, both GC fingerprints resulted from the relative retention indices (RRI) and the recorded MS of the separated compounds. The two criteria have been quantified by their correlation with the standards. A new parameter called global composition evaluation index (I(GCMS)), which resulted from a well-balanced average of the two criteria, has been defined. Because the comparison of the results of the MS with databases is more accurate than the RRI, we considered that the ratio of the two criteria must be at least GC:MS 1:2. A database containing RRI of about 600 components, widely found in essential oils composition and separated on HP-5 column, was created. Two macros based on the Microsoft Excel spreadsheet were also created. The program offers the best 20 matches of each compound with the combined MS and RRI library. The composition of Romanian Acorus calamus L. essential oil was established and the results were compared with those obtained by 'classical' methods.

Gas Chromatography-Mass Spectrometry↗

PubMed1997

Phase I/II study of intraperitoneal floxuridine and platinums (cisplatin and/or carboplatin).

Previous studies have shown that intraperitoneal (i.p.) floxuridine (FUDR) is tolerated at a dose of 3 g x 3 days given in 1.5-2 L of normal saline (NS). In a randomized phase II trial by the Southwest Oncology Group, this treatment was selected for further study because of a favorable 1-year progression-free survival. We have now evaluated ip FUDR in full doses combined with i.p. cisplatin given on the third day at a dose of 60 mg/m2 in 500 mL of NS. Intraperitoneal carboplatin was partially or fully substituted for i.p. cisplatin in patients with symptomatic neuropathies. All patients also received i.p. leucovorin, as previously piloted for fluoropyrimidine modulation. Seven patients with symptomatic ascites or measurable tumors were entered, as were 11 asymptomatic patients with minimal residual (< or = 1 cm) epithelial ovarian cancer. Six cycles of the combination of i.p. FUDR + cisplatin were completed in three patients; however, the combination of FUDR with both platinums was particularly well tolerated. Intraperitoneal FUDR + carboplatin (AUC of 5) was associated with some grade 3 and 4 thrombocytopenia and neutropenia. Eight of these 11 patients are alive, and 3 have been continuously with no evidence of disease exceeding 32 months. The regimen of i.p. FUDR + i.p. cisplatin (or i.p. FUDR with both platinums) is suitable for a phase III trial testing i.p. therapy either from the outset (e.g., i.p. up front) or after achieving clinical complete responses from initial treatment without intervening relapse (i.e., i.p. consolidation) in comparison to i.p. cisplatin.

Adult↗

PubMed1997

Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation.

PURPOSE: A phase II study of liposomal doxorubicin was conducted in patients with ovarian cancer who failed to respond to platinum- and paclitaxel-based regimens. Liposomal doxorubicin was selected as a result of its superior activity against ovarian cancer xenografts relative to free doxorubicin and activity in refractory ovarian cancer patients that was noted during the phase I study. PATIENTS AND METHODS: Thirty-five consecutive patients were accrued in two institutions (22 in one and 13 in the other). All had progressive disease after either cisplatin or carboplatin and paclitaxel, or at least one platinum-based and one paclitaxel-based regimen. Patients received intravenous (I.V.) liposomal doxorubicin 50 mg/m2 every 3 weeks with a dose reduction to 40 mg/m2 in the event of grade 3 or 4 toxicities, or a lengthening of the interval to 4 weeks (and occasionally to 5 weeks) with persistence of grade 1 or 2 toxicities beyond 3 weeks. RESULTS: Nine clinical responses (one complete response [CR], eight partial responses [PRs]) were observed in 35 patients (25.7%), with seven of these having been confirmed by two consecutive computed tomographic (CT) measurements. The median progression-free survival was 5.7 months with an overall survival of 1.5 to 24+ months (median, 11 months). Although 13 patients experienced grade 3 or 4 nonhematologic skin and mucosal toxicities (either hand-foot syndrome or stomatitis), with dose modifications, the treatment was very well tolerated. Nausea that was clearly attributable to the drug, hair loss, extravasation necrosis, or decreases in ejection fraction did not occur. CONCLUSION: Liposomal doxorubicin has substantial activity against ovarian cancer refractory to platinum and paclitaxel. The responses achieved with liposomal doxorubicin were durable and maintained with minimal toxicity. This liposomal formulation should be evaluated further in combination with other drugs in less refractory patients.

Aged↗