Application and safety of erythropoietin in cancer management.
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Anemia↗
Biomedical subjects
R Pirker
Publications and source records attributed to R Pirker.
Simultaneous determination of gentisic, salicyluric and salicylic acid in human plasma using solid-phase extraction, liquid chromatography and electrospray ionization mass spectrometry.
A method is developed for the simultaneous extraction of gentisic (GA), salicyluric (SUA) and salicylic acid (SA) in human plasma from Willow Bark extract, by solid phase extraction (SPE) using Waters Oasis HLB (divinylbenzene-n-vinylpyrrolidone copolymer) cartridges. Also, a method is optimized comprising of reversed-phase (RP) high-performance liquid chromatography (HPLC) in connection with electrospray ionization mass spectrometry (ESI-MS), fluorescence detection (FLD) and photo diode array detection (DAD) to identify and quantify GA, SUA and SA in the SPE effluents. An improved sensitivity regarding the lower detection limit (LOD) of < 7 ng/ml, the limit of quantitation (LOQ) of 20 ng/ml and short analysis times of < 15 min is required. The validated SPE method shows linearity in the range of 9.0-58.2 ng/ml for GA, 9.4-191.5 ng/ml for SUA and 12.8-1101.6 ng/ml for SA. The correlation coefficient values are > 0.9994 and 0.99 for fluorescence detection (FLD) and electrospray ionization mass spectrometry (ESI-MS), respectively. The recoveries are from 91.3-102.1% for gentisic acid (GA), 86.8-100.5% for salicyluric acid (SUA) and 75.8-81.4% for salicylic acid (SA) depending on the starting concentrations. RP-LC-ESI-MS/MS studies using collision induced dissociation (CID) confirm that the investigated analytes are not artifacts and facilitate further specific identification in addition to the determination of the parent ion mass even in the presence of co-eluting peaks. The established method is also used to analyze gentisic (GA), salicyluric (SUA) and salicylic acid (SA), not only after intake of Willow Bark capsules (Assalix, BNO 1455) but also as naturally occurring constituents in human plasma after the intake of salicylic acid containing foods.
Calibration↗
Expression of resistance markers to methotrexate predicts clinical improvement in patients with rheumatoid arthritis.
BACKGROUND: Methotrexate is transported into the cell by the reduced folate carrier (RFC) and out of the cell by members of the multidrug resistance protein family (MRP). Transport proteins may affect the therapeutic efficacy of this drug in patients with rheumatoid arthritis. OBJECTIVE: To investigate the potential benefit of the presence of RFC and the absence of functional MRP for the efficacy of methotrexate treatment. METHODS: The study involved 163 patients (116 female, 47 male; mean age 59.5 years) on methotrexate (mean weekly dose 12.2 mg). RFC was determined using reverse transcriptase polymerase chain reaction, and MRP function by flow cytometry, using a calcein acetoxymethylesther/probenecid assay. Clinical response to methotrexate was evaluated by the EULAR response criteria and the ACR 20% improvement criteria. The clinical data were obtained at the beginning of methotrexate treatment and at the time of blood sampling during ongoing therapy. Patients were divided into four groups according to the presence (+) or absence (-) of RFC and functional (f) MRP. RESULTS: fMRP+/RFC+ and fMRP-/RFC- patients more often had good EULAR response rates (60%, p = 0.014, and 53%, p = 0.035, respectively) in comparison with the fMRP-/RFC+ group (29%); fMRP+/RFC- patients had a low frequency of good disease activity responses. CONCLUSIONS: Absence of fMRP plus presence of RFC did not prove to be related to beneficial effects of methotrexate, but the lack or the presence of both fMRP and RFC led to a significantly better therapeutic outcome. Determination of these markers may predict responsiveness to methotrexate.
Antirheumatic Agents↗
Darbepoetin alfa in lung cancer patients on chemotherapy: a retrospective comparison of outcomes in patients with mild versus moderate-to-severe anaemia at baseline.
GOALS: Currently, there is some debate concerning the haemoglobin level at which treatment of anaemia with erythropoiesis-stimulating agents should be initiated in cancer patients on chemotherapy. We report several analyses of data from a phase III trial of darbepoetin alfa versus placebo, comparing outcomes for patients with mild and moderate-to-severe anaemia. PATIENTS AND METHODS: Data were obtained from a phase III trial of darbepoetin alfa versus placebo in anaemic patients with lung cancer receiving chemotherapy ( n=314). Outcomes were compared for patients with baseline haemoglobin > or =10-11 g/dl and <10 g/dl. RESULTS: Darbepoetin alfa significantly reduced transfusions compared with placebo, irrespective of haemoglobin level at treatment initiation. For patients with baseline haemoglobin <10 g/dl, 31% and 59% of those receiving darbepoetin alfa and placebo, respectively, required a transfusion from week 5 to the end of the treatment phase ( P<0.038). For patients with baseline haemoglobin > or =10 g/dl, the proportions were 15% and 41%, respectively ( P<0.001). Darbepoetin alfa also improved fatigue compared with placebo in both haemoglobin categories. CONCLUSIONS: These findings show that initiating treatment at haemoglobin levels both <10 g/dl and > or =10-11 g/dl results in substantial clinical benefits, supporting the use of erythropoietic therapy also in patients with mild anaemia.
Adult↗
Consensus: the follow-up of the treated patient.
This is the first consensus document on the follow-up of the treated patient with non-small cell lung cancer that has been written by this group. The document has been drawn up by doctors coming from many different cultures and philosophical backgrounds. It acknowledges that there are published guidelines on the follow-up particularly those in trials, and does not wish to contradict these. There is lack of evidence-based medicine to recommend a strong general policy in this area. For those patients who were treated with curative intent the initial follow-up will depend upon the toxicity that is evident from the treatment given. Thereafter the interval between follow-up visits should be every 3 months for the first two years, then every 6 months for up to five years. Rapid and easy access to the multidisciplinary team should be available. Full examination and chest X-ray should be carried out on each visit but other investigations should be determined by clinical need. For those patients treated with palliative intent the interval between follow-up visits once the acute reactions have settled will depend upon the adequacy of the control of the symptom and the availability of separate palliative care teams. At all times the patient should have rapid access to the multidisciplinary team and in general frequent follow-up, that is at intervals of one to two months, may be appropriate during the first six months. Follow-up constitutes an important part of lung cancer management. Efforts should be made to gain clinical material to give us evidence-based guidelines.
Carcinoma, Non-Small-Cell Lung↗
Simultaneous determination of hypericin and hyperforin in human plasma and serum using liquid-liquid extraction, high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry.
A method for the simultaneous extraction of hypericin and hyperforin from a St. John's Wort extract, which is used in case of moderate depressions and skin injuries, from human plasma and serum by liquid-liquid extraction (LLE) with n-hexane-ethylacetate (70:30, w/w) was developed. A reversed-phase high-performance liquid chromatographic (RP-HPLC) method with UV, fluorescence (FLD) and mass spectrometric (MS) detection using electrospray ionization (ESI) was used to identify and quantify hypericin and hyperforin in the extracts from blood samples. Linearity was obtained in the ranges 8.4-28.7 ng/ml (hypericin) and 21.6-242.6 ng/ml (hyperforin). Recoveries were between 32.2 and 35.6% for hypericin and 100.1 and 89.9% for hyperforin. Intra-day accuracy and precision for this method ranged between 3.2 and 4.3% and 2.6 and 2.8%, respectively. After validation of the LLE, the method was tested on real plasma samples which were obtained by ingestion of St. John's Wort extract capsules. Blood samples were taken 2, 4, and 6 h after ingestion. Finally, this method proved to be highly suitable for clinical and pharmacologically relevant studies.
Anthracenes↗
Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial.
BACKGROUND: The combination of paclitaxel with cisplatin or carboplatin has significant activity in non-small-cell lung cancer (NSCLC). This phase III study of chemotherapy-naïve advanced NSCLC patients was designed to assess whether response rate in patients receiving a paclitaxel/carboplatin combination was similar to that in patients receiving a paclitaxel/cisplatin combination. Paclitaxel was given at a dose of 200 mg/m(2) (3-h intravenous infusion) followed by either carboplatin at an AUC of 6 or cisplatin at a dose of 80 mg/m(2), all repeated every 3 weeks. Survival, toxicity and quality of life were also compared. PATIENTS AND METHODS: Patients were randomised to receive one of the two combinations, stratified according to centre, performance status, disease stage and histology. The primary analyses of response rate and survival were carried out on response-evaluable patients. Survival was also analysed for all randomised patients. Toxicity analyses were carried out on all treated patients. RESULTS: A total of 618 patients were randomised. The two treatment arms were well balanced with regard to gender (83% male), age (median 58 years), performance status (83% ECOG 0-1), stage (68% IV, 32% IIIB) and histology (38% squamous cell carcinoma). In the paclitaxel/carboplatin arm, 306 patients received a total of 1311 courses (median four courses, range 1-10 courses) while in the paclitaxel/cisplatin arm, 302 patients received a total of 1321 courses (median four courses, range 1-10 courses). In only 76% of courses, carboplatin was administered as planned at an AUC of 6, while in 96% of courses, cisplatin was given at the planned dose of 80 mg/m(2). The response rate was 25% (70 of 279) in the paclitaxel/carboplatin arm and 28% (80 of 284) in the paclitaxel/cisplatin arm (P = 0.45). Responses were reviewed by an independent radiological committee. For all randomised patients, median survival was 8.5 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm [hazard ratio 1.20, 90% confidence interval (CI) 1.03-1.40]; the 1-year survival rates were 33% and 38%, respectively. On the same dataset, a survival update after 22 months of additional follow-up yielded a median survival of 8.2 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm (hazard ratio 1.22, 90% CI 1.06-1.40; P = 0.019); the 2-year survival rates were 9% and 15%, respectively. Excluding neutropenia and thrombocytopenia, which were more frequent in the paclitaxel/carboplatin arm, and nausea/vomiting and nephrotoxicity, which were more frequent in the paclitaxel/cisplatin arm, the rate of severe toxicities was generally low and comparable between the two arms. Overall quality of life (EORTC QLQ-C30 and LC-13) was also similar between the two arms. CONCLUSIONS: This is the first trial comparing carboplatin and cisplatin in the treatment of advanced NSCLC. Although paclitaxel/carboplatin yielded a similar response rate, the significantly longer median survival obtained with paclitaxel/cisplatin indicates that cisplatin-based chemotherapy should be the first treatment option.
Adult↗
New drugs in the palliative chemotherapy of advanced non-small-cell lung cancer.
In inoperable advanced non-small-cell lung cancer (NSCLC), palliative chemotherapy is established and aims at palliation of symptoms, improvement of quality of life and prolongation of survival. In the last years, several new drugs with enhanced activity towards NSCLC and improved toxicity profile have been characterised, for example vinorelbine, gemcitabine, paclitaxel and docetaxel. Data from randomised trials suggest that regimens containing new drugs are more active than older combinations. Platin-based combinations of either vinorelbine, gemcitabine or paclitaxel have resulted in better outcome than cisplatin alone and new drugs in combination with platins are more active than the corresponding single agent. Non-platin-based combinations must be considered investigational until their non-inferiority to platin-based protocols has been proven in randomised trials on large patient populations. Patients with good performance status and adequate organ function should receive platin-based chemotherapy that includes the new drugs (vinorelbine, gemcitabine, paclitaxel or docetaxel). New drugs without platins are suitable for elderly patients and patients with poor performance status. Second-line chemotherapy prolongs survival in selected patients and should be particularly offered to patients with good performance status.
Antineoplastic Agents↗
Front-line treatment of advanced non-small-cell lung cancer with MTA (LY231514, pemetrexed disodium, ALIMTA) and cisplatin: a multicenter phase II trial.
BACKGROUND: To evaluate the activity of MTA plus cisplatin in chemotherapy-naive patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-six chemotherapy-naïve patients with NSCLC received 500 mg/m2 MTA plus 75 mg/m2 cisplatin every 21 days, with 4 mg dexamethasone orally twice daily on the day before, of, and after MTA administration. RESULTS: Median age was 58 years. WHO performance status was 0-2. Eighteen patients each had stage IIIB and IV disease. Seventeen patients each had squamous-cell and adenocarcinoma; two had undifferentiated disease. Fourteen patients (39%; 95% confidence interval: 23%-57%) showed partial response; seventeen (47%) had stable disease. Median survival was 10.9 months. Twenty-one patients (59%) experienced grade 3 or 4 granulocytopenia without fever or infection. Five (14%) and six (17%) patients experienced grade 3 anemia and grade 3 or 4 thrombocytopenia, respectively. Nonhematological toxicities included grade 3 nausea in two patients (6%), and grade 3 and 4 diarrhea in one patient (3%) each. One patient each experienced grade 4 ALT and grade 3 bilirubin and AST elevations. CONCLUSIONS: MTA plus cisplatin is well tolerated and active against NSCLC. Further studies of this combination are warranted.
Adult↗
Vinorelbine-gemcitabine in advanced non-small-cell lung cancer (NSCLC): an AASLC phase II trial. Austrian Association for the Study of Lung Cancer.
PURPOSE: The purpose of the present phase 11 trial was to determine the efficacy and toxicity of vinorelbine-gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: From December 1997 to February 1999, 78 chemotherapy-naive patients (median age 60 years, Karnofsky performance status of 100, 90, 80 and 70 present in 5%, 41%, 36% and 18% of the patients, respectively) with stage IIIB (17%) or IV (83%) NSCLC (65% adenocarcinomas, 22% squamous-cell carcinomas, 10% large-cell carcinomas, 3% mixed-cell carcinomas) received 25 mg/m2 vinorelbine and 1200 mg/m2 gemcitabine on days 1, 8 and 15 of a four-week cycle. RESULTS: In an intent-to-treat analysis, partial responses were seen in 19% of the patients. The median duration of response was 4.4 months. The median survival time was seven months and the one-year survival rate was 32%. Myelosuppression was the main side effect with WHO grade 3/4 neutropenia and thrombocytopenia in 35% and 11% of the patients, respectively. Other side effects were usually mild to moderate. CONCLUSIONS: Vinorelbine-gemcitabine is active, well tolerated and easy to administer on an outpatient basis in advanced NSCLC. Thus a randomized comparison of this combination with platinum-based protocols is warranted in patients with advanced NSCLC.
Adult↗
Drug resistance factors in acute myeloid leukemia: a comparative analysis.
To compare the clinical relevance of drug resistance factors in de novo acute myeloid leukemia (AML), we determined their relationship to both response to induction chemotherapy and survival of the patients in univariate as well as multivariate analyses. The drug resistance factors immunocytochemically studied in 111 patients at the time of diagnosis included the lung resistance protein (LRP), P-glycoprotein (P-gp), multidrug resistance protein (MRP1) and bcl-2. In the univariate analyses, age (P = 0.005), karyotype (P = 0.03), LRP (P = 0.003), P-gp (P = 0.02) and bcl-2 (P = 0.03) predicted for response to induction chemotherapy, whereas MRP1 had no predictive value. Age (P = 0.05), karyotype (P = 0.05) and LRP (P = 0.03) retained their predictive value in the multivariate logistic regression analyses. With regard to overall survival, age (P = 0. 008), karyotype (P = 0.006), LRP (P = 0.001) and P-gp (P = 0.01) were of prognostic value in the univariate Cox regression analyses but only age (P = 0.01), karyotype (P = 0.02) and LRP (P = 0.01) retained their prognostic significance in the multivariate analyses. A risk score based on the number of independent prognostic factors allowed division of patients into four groups with different outcome. In these groups, the complete remission rates were 93%, 75%, 47% and 33%, respectively, and median overall survival was 2.4, 1.2, 0.6 and 0.2 years, respectively. Thus, several drug resistance factors did predict outcome in the univariate analyses but LRP was the only drug resistance factor with independent predictive and prognostic significance. The proposed risk score might be useful for risk-adapted treatment in the future. Leukemia (2000) 14, 68-76.
Acute Disease↗
Clinical relevance of the lung resistance protein in diffuse large B-cell lymphomas.
Drug resistance of non-Hodgkin's lymphomas may involve mechanisms of the multidrug resistance phenotype including the lung resistance protein (LRP) and the multidrug resistance protein (MRP1). To determine the clinical relevance of these multidrug resistance factors in previously untreated diffuse large B-cell lymphomas (n = 48), we studied LRP and MRP1 expression in lymphoma cells and their impact on clinical outcome. LRP and MRP1 expression were immunohistochemically assessed by means of the monoclonal antibodies LRP-56 and MRPr1, respectively. LRP was positive in 23% and MRP1 in 44% of the samples. LRP expression was associated with higher tumor stage (P = 0.03), elevated serum lactate dehydrogenase levels (P = 0.01), and the International Prognostic Index (P = 0.0001). LRP-positive patients had a lower complete response rate to polychemotherapy than LRP-negative patients (18 versus 65%; P = 0.006). Patients with LRP expression had a shorter overall survival than those without LRP expression (median of 0.9 years versus median not reached; P = 0.001). MRP1 expression was independent of clinical and laboratory parameters and had no impact on the outcome of chemotherapy or survival of the patients. These data suggest that LRP expression but not MRP1 expression is an important mechanism of drug resistance associated with worse clinical outcome in previously untreated diffuse large B-cell lymphomas. Thus, the reversal of LRP-mediated drug resistance may improve clinical outcome in diffuse large B-cell lymphoma in the future.
ATP-Binding Cassette Transporters↗
The lung resistance protein (LRP) predicts poor outcome in acute myeloid leukemia.
To determine the clinical significance of the lung resistance protein (LRP) in acute myeloid leukemia (AML), we have studied LRP expression of leukemic blasts and its association with clinical outcome in patients with de novo AML. LRP expression of leukemic blasts was determined by immunocytochemistry by means of monoclonal antibody LRP-56. LRP expression at diagnosis was detected in 31 out of 86 (36%) patients and correlated with white blood cell count (p = 0.01). The complete remission rate of induction chemotherapy was 72% for all treated patients (n = 82). The complete remission rate was 81% for patients without LRP expression but only 55% for patients with LRP expression (p = 0.01). Overall survival and disease-free survival were estimated according to Kaplan-Meier in 82 and 59 patients, respectively. At a median follow-up of 16 months, median overall survival was 17 months for LRP-negative patients but only 8 months for LRP-positive patients (p = 0.006). Disease-free survival was 9 months for LRP-negative patients and 6 months for LRP-positive patients (p = 0.078). Thus LRP predicts for poor outcome indicating that the LRP gene is a clinically relevant drug resistance gene in AML.
Adolescent↗
MRP expression in acute myeloid leukemia. An update.
To determine the clinical significance of the multidrug resistance protein (MRP) in patients with de novo AML, we have studied MRP expression of leukemic cells at diagnosis and its association with clinical outcome in 127 patients. MRP expression was determined by immunocytochemistry by means of monoclonal antibodies QCRL-1/QCRL-3. MRP expression was low, intermediate and high in 30%, 46% and 24% of the patients, respectively. MRP expression was independent of age and sex of the patients, white blood cell count, FAB subtype, serum lactate dehydrogenase levels and karyotype aberrations. MRP expression had no impact no response to induction chemotherapy. The complete remission rates were 75%, 70% and 64% for patients with low, intermediate and high expression, respectively. Patients with intermediate or high MRP expression showed a trend toward shorter overall survival (p = 0.09) as compared to patients with low MRP expression. MRP does not predict for response to induction chemotherapy but intermediate or high MRP expression might be associated with shorter overall survival of the patients.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Advanced non-small-cell lung cancer: adjunctive interferon gamma in induction and maintenance therapy.
PURPOSE: To evaluate the feasibility of interferon gamma (IFNgamma) as an adjunct to chemotherapy in advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 32 patients were recruited and received 25 mg/m2 cisplatin and 100 mg/m2 etoposide on days 8, 10 and 12 every 3 weeks for a total of three cycles. A dose of 100 microg IFNgamma was given subcutaneously three times weekly from days 1 to 8 and between days 15 and 29. After induction, all patients except those with progressive disease were offered IFNgamma maintenance therapy: 100 microg three times weekly. RESULTS: The following responses were obtained: partial response, 5 (16%); minor response, 12 (37%); stable disease, 4 (13%); progressive disease, 11 (34%). The survival rates after 1 and 2 years were 47% and 25% respectively. Patients receiving maintenance IFNgamma had a 2-year survival rate of 58%. Toxic side-effects were rare and included grade III/IV fever (7%/1%) and grade III/IV leucopenia (4%/1%). CONCLUSIONS: In patients with advanced NSCLC, an adjunctive dose of 100 microg IFNgamma, given three times weekly in the induction and maintenance phase, is feasible. Survival data seem favourable so this regimen may warrant further investigation in a phase III study.
Adult↗
The TP53 genotype but not immunohistochemical result is predictive of response to cisplatin-based neoadjuvant therapy in stage III non-small cell lung cancer.
BACKGROUND: The cytotoxic effects of cisplatin and anthracyclins have been attributed to apoptosis induction, which has been recognized as a major function of the TP53 gene. The TP53 gene appears to be mutated in about 50% of cases of non-small cell lung cancer. A possible dependence of chemotherapy response on TP53 genotype was evaluated retrospectively in a group of patients with advanced non-small cell lung cancer and induction treatment. METHODS: Patients with complete or partial remission were compared with those with stable or progressive disease with respect to TP53 genotype and overall survival. Mutations in the TP53 gene were detected by complete direct sequencing (exons 2-11). RESULTS: A normal TP53 genotype proved to be significantly associated with major response to chemotherapy (P <.001). Overall, no association was found between p53 protein expression and TP53 genotype. A normal TP53 genotype was found to be highly sensitive in predicting response to treatment, whereas a mutant genotype was revealed to be specific in predicting lack of response. The difference in overall length of survival was significant between patients exhibiting a normal TP53 genotype (corresponding to those whose disease responded to chemotherapy) and patients showing mutant TP53 genotype (corresponding to those who had disease resistant to chemotherapy, P =.027). CONCLUSIONS: In a small cohort of patients with advanced non-small cell lung cancer we found a direct link between normal TP53 genotype and response to cisplatin-based induction treatment and also between mutant genotype and resistance to treatment, whereas p53 immunohistochemical result was predictive of neither.
Antineoplastic Combined Chemotherapy Protocols↗
Treatment of small cell lung cancer patients.
Small cell lung cancers, comprising approximately 20% of lung cancers, are rapidly growing and disseminating carcinomas which are initially chemosensitive but acquire drug resistance during the course of disease. Thus, outcome is poor with median survival of 10-16 months for patients with limited and 7-11 months for patients with extensive disease. Polychemotherapy with established drugs (platins, etoposide, anthracyclines, cyclophosphamide, ifosfamide and Vinca alkaloids) plays the major role in the treatment of this disease and results in overall response rates between 80%-95% for limited disease and 60%-80% for extensive disease. Dose-intensified chemotherapy and high-dose chemotherapy with peripheral blood progenitor cell support were tested in several trials but their exact impact on outcome remains to be determined. New drugs including the taxanes (paclitaxel, docetaxel), the topoisomerase I inhibitors (topotecan, irinotecan), vinorelbine and gemcitabine are currently evaluated in clinical trials. In limited disease, thoracic radiotherapy improves survival and prophylactic cranial irradiation should be administered to those with a reasonable chance of cure.
Antineoplastic Agents↗
Expression of the lung resistance protein predicts poor outcome in patients with multiple myeloma.
Expression of the lung resistance protein (LRP) is associated with resistance to various anticancer drugs including melphalan and, therefore, may affect the clinical outcome in multiple myeloma (MM). To determine the clinical significance of LRP, we have compared LRP expression in bone marrow plasma cells with clinical parameters including response to chemotherapy and survival of previously untreated patients with MM (n = 72). LRP expression immunocytochemically assessed by means of the LRP-56 monoclonal antibody was positive (> or =10% staining plasma cells) in 44 (61%) samples. There was no correlation between LRP expression and age, sex, type of the paraprotein, serum creatinine, stage, beta2-microglobulin, serum lactate dehydrogenase, or C-reactive protein. However, LRP expression was more frequently observed in patients with a p53 deletion than in those without such a deletion (P = 0.01). The overall response rate for all of the patients evaluable for response to induction chemotherapy (n = 58) was 67%. The response rate was 87% for patients without LRP expression but only 54% for patients with LRP expression (P = 0.01). Kaplan-Meier analysis revealed that patients with LRP expression had a shorter overall survival (median, 33 months) than those without LRP expression (median not reached; P = 0.04). These data show that LRP expression is an important marker for clinical drug resistance and predicts a poor outcome in MM.
Adult↗