Peripheral Neuropathy In Multiple Myeloma Patients Treated with Lenalidomide

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5024-5024
Author(s):  
Carmen Castaneda ◽  
Lilia Weiss ◽  
Neil A. Minton ◽  
Alex Kim ◽  
John Freeman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Adverse Events ◽  
Median Time ◽  
Study Drug ◽  
Phase Iii ◽  
Immunomodulatory Activity ◽  
Pivotal Phase ◽  
History Of ◽  
Time To Onset

Abstract Abstract 5024 Background: Lenalidomide is an oral IMiD® immunomodulatory compound with a dual mechanism of action, namely tumoricidal and immunomodulatory activity. As demonstrated by 2 randomized, double-blind, placebo-controlled pivotal phase III registration trials, lenalidomide plus dexamethasone (Len/Dex) was well tolerated and achieved significant clinical efficacy and survival outcomes vs placebo plus Dex (PBO/Dex) in patients (pts) with relapsed/refractory multiple myeloma (MM) (Weber 2007; Dimopoulos 2007). In MM, the rate of symptomatic peripheral neuropathy (PN) is 3–13%, although the rate of subclinical neuropathy detected by electrophysiological studies or histopathological evaluation is estimated to be much higher (40-60%; Kwan 2007). Published incidence of PN has been notable with thalidomide (Thal) ranging from 0 to 90%, depending on pt characteristics, concomitant treatments, dose/exposure duration, and techniques for identifying PN. We present the result of our analysis of PN adverse events (AEs) reported with Len. Methods: Reports of PN from the 2 registration studies (MM-009, MM-010; data cutoff June and August 2005, respectively), and postmarketing safety reports (Dec 2005 to Dec 2009) were retrieved from Celgene clinical and safety databases utilizing the Preferred Terms for PN AEs within the PN Standardized MedDRA (v13.0) Query (SMQ) to obtain all possible cases. Severity grades were according to the NCI CTCAE (V3). Results: Clinical Studies 703 pts (353 Len/Dex; 350 PBO/Dex) from the 2 registration studies were included in this analysis. The proportion of pts with ≥1 Grade (G) 1–4 PN AEs and ≥1 serious adverse event (SAE) was similar between the Len/Dex and PBO/Dex arm (45.6% vs 44.9% and 1.1% vs 1.1%, respectively). However, the proportion of pts with ≥1 G3/4 PN was slightly higher with Len/Dex vs PBO/Dex (9.3% vs 5.1%). Among the Len/Dex pts with PN AEs, prior Thal or vincristine was reported in 39.1% and 60.9% of pts, respectively and 24.8% of pts had history of PN. Among the PBO/Dex pts with PN AEs, prior Thal or vincristine was reported in 46.5% and 58.0% of pts, respectively and 29.3% of pts had a history of PN. Within this SMQ analysis, the PN AEs reported in ≥5% of the pts were peripheral neuropathy, hypoaesthesia, paraesthesia, and muscle weakness in both treatment arms. 98.3% of PN AEs were not SAEs and 83.2% were G1/2 in the Len/Dex arm. Among pts in the Len/Dex arm and with PN AEs, PN resolved in 61.5% and study drug was continued in 78.9% of pts. Study drug was reduced due to PN in 12.4% and interrupted in 5.0% of pts in the Len/Dex arm. The median time to onset of PN event was longer in the Len/Dex arm compared with the PBO/Dex arm (41 vs 31 days). Postmarketing A total of 2857 PN AEs were reported in 2329 of an estimated 73,592 MM pts. The reporting rate of PN AEs is 3.2% in the MM indication. Within this SMQ analysis, the PN AEs reported in ≥0.5% of the pts were peripheral neuropathy, hypoaesthesia, and paraesthesia. 93.8% of PN AEs were not SAEs. Most pts were males and elderly with a median age of 66 yrs (range: 29–95). Among MM pts with PN AEs and available information, 13% had prior Thal, 5% had prior bortezomib, and 11% had a history of PN. In the majority of reports, outcome was unknown and Len was continued. The median time to onset of PN event was 60 days (range: 1–1460). Conclusion: In 2 pivotal phase III registration trials, the incidence rate of peripheral neuropathy adverse events was similar between the Len/Dex and PBO/Dex arms. Most pts had prior anti-myeloma therapies associated with PN and a quarter of the pts had a history of PN. Limited information in postmarketing reports on prior therapies and medical history may have underestimated pre-existing PN and exposure to prior anti-myeloma therapies associated with PN. PN AEs occurred within a median of 60 days of starting Len. In conclusion, peripheral neuropathy adverse events in MM pts treated with Len are generally not SAEs and did not commonly require dose modification or interruption. References Dimopoulos et al. NEJM 2007;357(21):2123-2132. Kwan JY. Neurol Clin 2007;25(1):47-69. Weber et al. NEJM 2007;357(21):2133-2142. Disclosures: Castaneda: Celgene: Employment. Weiss:Celgene: Employment. Minton:Celgene: Employment. Kim:Celgene: Employment. Freeman:Celgene: Employment. Yu:Celgene: Employment. Knight:Celgene: Employment.

Eight-year immunogenicity and safety of interferon beta-1a-Avonex®treatment in patients with multiple sclerosis

2005 ◽  
Vol 11 (4) ◽  
pp. 409-419 ◽  
Author(s):  
Robert M Herndon ◽  
Richard A Rudick ◽  
Frederick E Munschauer ◽  
Michele K Mass ◽  
Andres M Salazar ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Median Time ◽  
Interferon Beta ◽  
Phase Iii ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pivotal Phase ◽  
Phase Iii Trial ◽  
Laboratory Test Results ◽  
Phase Iii Study

An open-label extension study of the phase III trial of intramuscular interferon beta-1a (IFNβ-1a-Avonex) was conducted to evaluate the immunogenicity and safety of IFNβ-1a-Avonex over six years in patients with relapsing multiple sclerosis (MS). Patients who participated in the pivotal phase III study were offered enrolment; entry was also open to patients who had not participated. All patients received IFNβ-1a-Avonex 30 mg intramuscularly once weekly for six years, for a treatment duration of up to eight years in patients who received IFNβ-1a-Avonex in the phase III trial. Serum levels of IFNβ antibodies were measured every six months using a screening enzyme-linked immunosorbent assay (ELISA) followed by an antiviral cytopathic effect assay to detect neutralizing antibodies (NAbs) in serum samples positive on ELISA. The incidence of adverse events and laboratory test results assessed safety. Of 382 total patients, 218 had participated in the phase III study (103 placebo, 115 IFNβ-1a-Avonex) and 164 had not participated; 24 of the 164 were IFNβ-naïve. At baseline, 281 patients were negative for IFNβ antibodies (NAb-). NAbs (titre≥ 20) developed at any time over six years in 5% of these patients. Of 140 patients who had been on IFNβ-1b-Betaseron, 49 were positive for NAbs (NAb+) at baseline; 11 of 115 who had been on IFNβ-1a-Avonex were NAb+ at baseline. Thirty-nine of 49 patients who had been on Betaseron and were NAb+ had titres <100; 36 of these 39 seroconverted to NAb-while on IFNβ-1a-Avonex, with a median time of approximately six months. Ten patients who had been on Betaseron had NAb titres ≥ 100; five remained NAb+ during six years on IFNβ-1a-Avonex and five seroconverted to NAb-, but only after at least two years. Five patients who had been on IFNβ-1a-Avonex during the clinical trial were NAb+ with titres <100 at baseline; four seroconverted to NAb-, with a median time of two to three years. Six patients who had been on IFNβ-1a-Avonex had NAb titres ≥100; five of these remained NAb+ at six years. No patient with a NAb titre >1000 seroconverted to NAb-, whether initially treated with IFNβ-1a-Avonex or -Betaseron. Adverse events were similar to those observed in the pivotal phase III trial. Results from this trial indicated that IFNβ-1a-Avonex was associated with a low incidence of NAbs and was well tolerated for up to eight years. Further, the results indicate that persistence of NAbs is dependent on titre and IFNβ product.

Features and Risk Factors of Peripheral Neuropathy during Treatment of Advanced Multiple Myeloma with Bortezomib.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5098-5098
Author(s):  
Jean El-Cheikh ◽  
Anne Marie Stoppa ◽  
Segolene Duran ◽  
Reda Bouabdallah ◽  
Norbert Vey ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Dose Reduction ◽  
Median Time ◽  
Median Duration ◽  
Univariate Analysis ◽  
Autologous Transplantation ◽  
Prior History ◽  
History Of

Abstract Bortezomib has demonstrated activity and safety in heavily pretreated patients with relapsed and/or refractory multiple myeloma (MM). Peripheral neuropathy (PN) is among the most frequent adverse events reported with bortezomib, requiring dose-adjustment and careful patient-clinical monitoring. The aim of this retrospective single centre study was to determine the frequency, characteristics, and reversibility of PN from bortezomib treatment of 100 consecutive advanced MM patients treated with bortezomib 1.0 or 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11, every 21 days. PN was evaluated by investigator neurological examination at baseline, during the study, and at last follow-up. Patients characteristics at baseline prior to bortezomib initiation were as follow: median age: 60 (range, 27–77), prior history of diabetes: n=8 (8%), prior autologous transplantation: n=76 (76%), prior treatment with thalidomide: n=75 (75%) with a median dose of 200 (range, 50–600) mg for a median duration of 8 (range, 1–61) months. Median duration between thalidomide discontinuation and bortezomib initiation was 5 (range, 0–43) months. Before treatment with bortezomib, 48 patients (48%) already had some form of PN [grade 1, n=27 (56%); grade 2, n=16 (33%); grade 3, n=5 (11%)]. With a median follow-up of 8 (range, 0.1–32) months from bortezomib initiation, patients from this series received a median of 4 (range, 1–12) cycles of bortezomib. Bortezomib-related emergent PN was observed in 38 patients (38%; 95%CI, 28–47%), with grade 1, 2, 3, and 4 PN occurring in 17 (45%), 15 (39%), 5 (13%) and 1 (3%) patients respectively. Median time to onset of bortezomib-related PN was 53 (range, 11–182) days after bortezomib initiation. In most cases (n=30; 79%), patients had sensory symptoms, while 8 patients (21%) experienced both sensory and motor symptoms. Bortezomib-related PN led to dose reduction or discontinuation in 18 patients. Of the 38 patients with bortezomib-related PN, resolution to baseline or improvement occurred in 20 (53%) patients, at a median time of 3 (range, 1–8) months. In univariate analysis, comparing patients with and without bortezomib-related PN, prior history of treatment with thalidomide (P=0.009), patient baseline grade of PN at bortezomib initiation (P=0.04), number of bortezomib cycles administered (P=0.0005), and cumulative dose (mg) of bortezomib received by patients (P=0.001), were found to be significantly associated with the risk of emergence of bortezomib-related PN. In multivariate analysis, the total number of cycles of bortezomib (less or more than 4 cycles), and a prior history of treatment with thalidomide were the strongest parameters significantly associated with an increased incidence of bortezomib-related PN (P=0.03; OR=2.6; 95%CI, 1.1–6.1 and P=0.02; OR=3.9; 95%CI, 1.2–12.6 respectively). In all, we conclude that, though relatively frequent, bortezomib-associated PN seemed reversible in a majority of patients and manageable after dose reduction or discontinuation. However, the finding that the development of bortezomib-related PN seems to be dependent of the patient history of prior neurotoxic therapy (mainly thalidomide), raises the question of the optimal sequence and schedule of administration of these anti-MM effective drugs as single agents, but also in combination.

A randomized, double-blind, multicenter, phase III study of fosnetupitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving doxorubicin-cyclophosphamide/epirubicin-cyclophosphamide (AC/EC) based highly emetogenic chemotherapy: CONSOLE-BC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12094-12094
Author(s):  
Junji Tsurutani ◽  
Kazuo Matsuura ◽  
Kenichi Inoue ◽  
Yuko Tanabe ◽  
Tetsuhiko Taira ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Study Drug ◽  
Complete Response ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Pivotal Phase ◽  
Double Blind ◽  
History Of ◽  
Neurokinin 1 ◽  
To Receive

12094 Background: Fosnetupitant (FN) is a phosphorylated pro-drug of netupitant that has high binding affinity and selectivity for the neurokinin 1 receptor and a long half-life of 70 h. Recent studies have reported that fosaprepitant (FA) has a risk for developing injection site reactions (ISRs) in patients with breast cancer who receive doxorubicin-cyclophosphamide/epirubicin-cyclophosphamide (AC/EC)-based treatments. Previous studies have shown that FN may have a low risk of ISRs and could potentially address this unmet medical need. The present study (JapicCTI-194691) was intended to evaluate the safety profile, including ISRs, of FN in patients receiving AC/EC treatment. For exploratory purposes, we set the FA group as the exploratory arm. A separate pivotal phase 3 study (JapicCTI-194611) was conducted to verify the efficacy and safety of FN compared with FA in patients receiving cisplatin-based chemotherapy. Methods: Patients scheduled to receive AC/EC were randomly assigned 1:1 to receive FN 235 mg or FA 150 mg in a double-blind manner, in combination with intravenous palonosetron (PALO) 0.75 mg and dexamethasone (DEX) 9.9 mg on day 1. The stratification factors were age class ( < 55 years vs. ≥55 years) and site. The primary endpoint was the incidence of treatment-related adverse events (TRAEs) of FN. In addition, the ISRs were investigated as secondary endpoints. Efficacy outcomes were also evaluated as secondary endpoint. Results: Between April 2019 and March 2020, total 102 patients were enrolled in the study. Fifty-two patients were randomized to the FN group and 50 to the FA group, and all of them were treated with the study drug and evaluated for safety. The baseline characteristics were generally balanced, except for the history of motion sickness (54.9% vs. 44.9%) and non-smokers (78.4% vs. 63.3%) in the FN and FA groups, respectively, which are considered as risk factors for chemotherapy-induced nausea and vomiting. The primary endpoint, the incidence of TRAEs was 21.2% (n = 11) (95% CI 11.1% – 34.7%) in the FN group, which was similar to that in the FA group [22.0% (n = 11) (95% CI 11.5% - 36.0%) ]. Any cause or treatment-related ISRs were observed in 5.8% (n = 3) and 0% (n = 0), respectively, in the FN group and 26.0% (n = 13) and 10.0% (n = 5), respectively, in the FA group. The overall (0–120 h) complete response (no emetic event and no rescue medication) rate standardized by age category was 45.9% (n = 23) in the FN group and 51.3% (n = 25) in the FA group. Conclusions: The safety of FN in combination with PALO and DEX was favorable. Risk of ISR by FN was quite low in the AC/EC setting. Clinical trial information: JapicCTI-194691.

Comprehensive Analysis of Bortezomib-Induced Adverse Events Using the Japanese Real-World Database

Oncology ◽  
2021 ◽  
Author(s):  
Aya Satoki ◽  
Mayako Uchida ◽  
Masaki Fujiwara ◽  
Yoshihiro Uesawa ◽  
Tadashi Shimizu
Keyword(s):  
Peripheral Neuropathy ◽  
Adverse Events ◽  
Cardiac Failure ◽  
Tumor Lysis Syndrome ◽  
Adverse Event Reporting System ◽  
Japanese Patients ◽  
Comprehensive Analysis ◽  
Drug Event ◽  
Lung Disorder ◽  
Time To Onset

Background: Bortezomib is used as first-line therapy for multiple myeloma. Observational studies based on the FDA Adverse Event Reporting System (FAERS) database analysis and systematic reviews indicate that the incidence of peripheral neuropathy and tumor lysis syndrome (TLS) tends to be higher with bortezomib than that of other drugs. In a comprehensive analysis assessing drugs that cause peripheral neuropathy in Japanese patients, the incidence of bortezomib-induced adverse events (AEs) was reportedly high. However, a comprehensive assessment of bortezomib is lacking. Objectives: The purpose of this study was to determine the frequency of bortezomib AEs in Japanese patients and to determine the incidence, time to onset, and post hoc outcomes of unique AEs using the Japanese Adverse Drug Event Report (JADER) database. Method: To investigate the association between bortezomib and AEs, we analyzed the JADER database, which contains spontaneous AE reports submitted to the Pharmaceuticals and Medical Devices Agency from April 2004 to December 2020. Criteria indicating the presence of an AE signal were met when the following requirements were fulfilled: proportional reporting ratios (PRR) ≥ 2 and χ2 ≥ 4. Time to onset and post-event outcomes were analyzed for characteristic AEs. Results: Among 26 extracted AEs, 13 presented AE signals. The post-exposure outcomes of 12 AEs showed fatal outcomes at rates exceeding 10%, including cardiac failure (30%), lung disorder (24%), pneumonia (18%), and TLS (10%). Furthermore, a histogram of time to onset revealed that the 12 AEs were concentrated from the beginning to approximately one month after bortezomib administration. The median onset times for cardiac failure, lung disorder, pneumonia, and TLS were 28, 13, 42, and 5 days, respectively. Conclusions: Cardiac failure, lung disorder, pneumonia, and TLS had a higher rate of fatal clinical outcomes after onset than other AEs. These AEs exhibited a greater onset tendency in the early post-dose period. This study suggests that there is a need to monitor signs of cardiac failure, lung disorder, pneumonia, and TLS, potentially resulting in serious outcomes.

scholarly journals Perampanel in the treatment of partial seizures: Time to onset and duration of most common adverse events from pooled Phase III and extension studies

2015 ◽  
Vol 48 ◽  
pp. 45-52 ◽  
Author(s):  
David Ko ◽  
Haichen Yang ◽  
Betsy Williams ◽  
Dongyuan Xing ◽  
Antonio Laurenza
Keyword(s):  
Adverse Events ◽  
Phase Iii ◽  
Partial Seizures ◽  
Time To Onset

A Systematic Review and Meta-Analysis of Thalidomide in Patients with Previously Untreated Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3570-3570 ◽  
Author(s):  
Lisa Hicks ◽  
Adam Haynes ◽  
Donna E. Reece ◽  
Irwin Walker ◽  
Jordan A. Herst ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Relative Risk ◽  
Peripheral Neuropathy ◽  
Adverse Events ◽  
Response Rate ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Number Needed To Treat ◽  
Vte Prophylaxis ◽  
American Society

Abstract Background: Multiple myeloma disproportionately affects the elderly and is currently an incurable malignancy. New therapies for myeloma, particularly oral therapies, are urgently needed. Objectives: To determine if thalidomide with or without other agents, improves response rate (≥ 50% reduction in monoclonal protein), survival, and/or progression in patients with previously untreated myeloma. To determine the frequency and significance of major adverse events associated with thalidomide in this setting. Methods: A literature search of Medline (1966–June 2006), Embase (1980–June 2006), the Cochrane Library, abstracts from the annual meetings of the American Society of Hematology (1999–2005) and the American Society of Oncology (1999–2006) was completed with a pre-specified search strategy. No language restrictions were applied. Randomized controlled trials of induction thalidomide (any dose, any duration) for adults with previously untreated multiple myeloma were included. Trials of exclusively maintenance therapy were excluded. Two reviewers independently extracted data. The methodological quality of selected trials was assessed and summarized. Weighted data was expressed as relative risk, risk difference, number needed to treat (NNT), and number needed to harm (NNH). A random-effects model was used. Results: Six eligible studies involving almost two thousand patients (N=1875) were identified and meta-analyzed. Two studies were published and four were reported in abstract form only. Five studies reported overall response rate (ORR); the four largest trials reported statistically significant improvements in ORR with the addition of thalidomide to standard therapy. The weighted relative risk of responding to a thalidomide-containing regimen versus control was 1.50 (95% CI 1.21 to 1.86). The NNT to achieve one additional response with thalidomide was 4 (95% CI 2.9 to 8.3). Two trials reported improvements in EFS/PFS. One trial reported an improvement in OS. The risk of VTE, peripheral neuropathy, and constipation was consistently elevated with thalidomide such that for every 50 patients treated with a thalidomide-containing-regimen, one could expect 12 to 13 additional patients to respond, 4 additional patients to develop VTE (NNH 12.5; 95% CI 8.3 to 20), 2 additional patients to develop peripheral neuropathy (NNH 25; 95% CI 16.7 to 50), and 4 additional patients to develop constipation (NNH14; 95% CI 10 to 25). In our analyses, prophylactic anticoagulation appeared to decrease, but not abolish, the risk of VTE with thalidomide. Conclusions: Thalidomide improves response rate and possibly progression free and overall survival in patients with previously untreated myeloma. It also increases the incidence of VTE, neuropathy, constipation and other adverse events. Further studies are required to confirm the survival advantage seen in one study, and to determine the optimum strategy for VTE prophylaxis.

High-Dose Cyclophosphamide: An Effective Non-Transplant Salvage Option in Relapsed/Refractory Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4947-4947
Author(s):  
Sikander Ailawadhi ◽  
Michael Keng ◽  
Eddie Thara ◽  
Andrew Hendifar ◽  
Tanya Price ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Median Time ◽  
Clinical Benefit ◽  
Single Agent ◽  
Staging System ◽  
Median Number ◽  
High Dose ◽  
Advanced Stage ◽  
Stage Disease

Abstract Abstract 4947 Background Recent advances in the treatment of multiple myeloma (MM) have significantly improved overall survival. With MM patients living longer, there is a constant need to find better therapeutic options, especially when patients are refractory to conventional agents, and are not eligible for experimental therapeutics in clinical trials. We evaluated treatment with single-agent high-dose cyclophosphamide (HDCy) in a cohort of heavily pre-treated patients with relapsed/refractory MM. Methods All the patients were previously treated for active MM at the University of Southern California (USC), Los Angeles, CA. Cyclophosphamide was administered at 1.2 gm/m2 in D5W intravenous (IV) over 1 hour every 3 hours for a total of 4 doses. Mesna was given to prevent urinary adverse events from cyclophosphamide as 4 gm/m2 in 1000 ml D5W IV to run at 50 ml/hr for 20 hours, starting 15 minutes prior to the first dose of cyclophosphamide. Patients were given pre-medications with 5HT3 antagonists an steroids. Treatment was administered in the in-patient setting and patients were discharged after the last dose of cyclophosphamide. Treatment was repeated every 4 weeks, if well-tolerated and continued response. Growth factor support was provided to the patients, as needed. Response to treatment was assessed after each 4-week cycle according to the International Uniform Response Criteria for MM. Results Seven patients (4 females, 3 males) were treated on this regimen with a median age of 53 years (range 34-61 yrs). These patients included 3 Hispanics (43%), 2 Asians (29%), 1 Caucasian (14%) and 1 African-American (14%). MM subtype was IgG disease in 3, IgA in 2, and light-chain only in 2 patients. Advanced stage disease (>stage 1) at the time of diagnosis as per the Durie Salmon (DS) staging system was present in 71% of the patients, while 3 patients (43%) had advanced stage disease as per the International Staging System (ISS). Four patients (57%) had lytic bone disease at the time of diagnosis, while only 1 patient was a non-secretor. Five of these patients (71%) never received an autologous stem cell transplant (ASCT) as a part of their MM treatment. Median number of therapies in these patients was 5 (range 4-8), while median number of therapies prior to high-dose cyclophosphamide (HDCy) were 3 (range 2-7). Median number of cycles of HDCy administered to the patients was 2 (range 1-5). Overall Response Rate (ORR = CR+PR) was 29% (n=2) with 1 patient achieving CR and 1 patient achieving VGPR. Four patients (57%) had stable disease (SD) and 1 patient had progressive disease (PD). Thus, the overall clinical benefit (CR+PR+SD) was seen in 6 out of the 7 patients (86%). Median time to best response was 5 weeks (range 4-10 weeks). Median time to progression was 16 weeks (range 8-24 weeks). Most common adverse events were cytopenias and fatigue, but were easily manageable with supportive care on an out-patient basis. Conclusions Despite improvement in therapeutic regimens for MM, it remains an incurable disorder. There is a constant need to develop regimens for treatment of relapsed/refractory MM patients that are efficacious and well-tolerated. We report the use of single-agent HDCy in heavily pre-treated MM patients. Despite the small number of patients studied, we have noted meaningful clinical benefit with a manageable toxicity profile. This warrants further investigation into developing therapeutic regimens with high-dose cyclophosphamide. Disclosures No relevant conflicts of interest to declare.

Economic evaluation of DVd versus VAd in the treatment of multiple myeloma: Results from a phase III multicenter randomized clinical trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6050-6050
Author(s):  
R. M. Rifkin ◽  
M. Hussein ◽  
R. Iskandar ◽  
A. O’Sullivan ◽  
D. Thompson ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Economic Evaluation ◽  
Drug Administration ◽  
Study Drug ◽  
Phase Iii ◽  
Study Drug Administration ◽  
Reduced Dose ◽  
Hospitalization Costs

6050 Background: A randomized Phase III clinical trial of pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone (DVd) versus conventional doxorubicin, vincristine, and reduced-dose dexamethasone (VAd) found similar efficacy in the treatment of newly-diagnosed multiple myeloma (Cancer, in press). However, observed clinical advantages of DVd included less toxicity and supportive care. (Cancer In press). Methods: This economic evaluation was conducted as a piggyback to the clinical trial. Utilization data were collected prospectively for enrolled patients (DVd = 97; VAd = 95). Costs were estimated by applying standard US unit costs in 2004 to observed utilization. We compared resource utilization and costs for study drug administration, other care (hospitalizations due to AEs, tests, transfusions, and concomitant medications), and total costs during follow-up for patients receiving DVd versus VAd using 2-sided t-tests. Results: DVd patients required significantly fewer hospital (1.5 vs 8.5; p < 0.01) and clinic days (4.8 vs 14.4; p < 0.01) for study drug administration. Costs of study drug were significantly higher for DVd patients ($16,181 vs $788; p < 0.01), but lower hospitalization costs ($3,311 vs $18,492; p < 0.01) and clinic costs ($797 vs $2,412; p < 0.01) for drug administration more than offset these costs, resulting in nominally lower overall study drug administration costs for DVd versus VAd ($20,289 vs $21,692; p = 0.64). No other component of care differed significantly between the two groups (costs of other care: $14,152 for DVd vs $14,154 for VAd; p = 0.99) and overall treatment costs ($34,442 for DVd vs $35,846 for VAd; p = 0.76) were similar in the two groups. DVd patients had approximately 10 additional days of follow-up over the trial period (149.4 vs 139.2) versus VAd patients. Conclusions: Despite higher drug acquisition costs, use of DVd did not increase the overall cost of treatment compared to VAd. [Table: see text]

Subgroup analysis of efficacy and safety analysis of a randomized, double-blinded controlled phase II study of STA-4783 in combination with paclitaxel in patients with metastatic melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8528-8528 ◽  
Author(s):  
S. O'Day ◽  
R. Gonzalez ◽  
D. Lawson ◽  
R. Weber ◽  
L. Hutchins ◽  
...  
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Subgroup Analysis ◽  
Single Agent ◽  
Study Drug ◽  
Progression Free Survival ◽  
Additional Treatment ◽  
Phase Iii ◽  
Rapid Progression ◽  
Double Blinded

8528 Background: STA-4783 (S), an inducer of heat shock protein 70 (hsp70) is a bis-thiobenzoylhydrazide compound. S leads to up-regulation of hsp70 in tumor cell lines. Xenograft models of solid tumors showed synergistic anti-tumor activity in combination with paclitaxel (P). The combination P + S, in phase I and II studies, showed dose-related hsp70 induction (evidence of biological activity) and tolerability. Methods: Eligibility was based on a diagnosis of metastatic cutaneous melanoma, ECOG <=2, and prior treatment with 1 or no chemotherapy regimens. A total of 81 patients (pts) were randomized 2:1 (P 80 mg/m2 + S 213 mg/m2:P 80 mg/m2) 3 weeks out of 4 at 21 US clinical sites. The primary endpoint was progression free survival (PFS); secondary endpoints were response rate (RR), and adverse events (AEs). Results: Based on intent-to-treat analysis, the median PFS was 3.68 months (m) for P + S vs. 1.84 m in the P only arm (p=.035). RR was 15.1% in the P + S arm and 3.6% in the P arm. Subgroup analysis showed chemo- naive pts (n=23) with P + S showed a median PFS of 8.28 m vs. 2.40 in the P arm (n=9). For pts with 1 prior chemotherapy, (n=29), PFS on P + S was 3.12 m vs. 1.77 m on P (n=19). Of 19 pts who crossed over at progression, data are available for 14. PFS ranged from 0.72 to 5.5 m. Three of the 14 evaluable pts treated with P alone had rapid progression (0.95, 1.6, and 1.7 m) then significant inversion of the time to progression with the addition of S to P (2.3, 5.5, and 4.2 m) suggesting study drug effect. Scans were done at identical intervals (8 weeks). The proportion of pts with AEs of grade 3 or higher was 54% (n=52) in the P + S group and 57% in the P group (n=28); pts on P received a median of 2 cycles, while pts in the P + S group received a median of 4. Adverse events leading to discontinuation were low in both groups: 10% for the P + S, and 14% for P. Conclusions: The addition of S to P showed an increase in PFS vs. P alone particularly in chemo-naïve pts. A few pts failing single agent P appeared to benefit from P + S. Despite the additional treatment duration in the P + S group the drugs were well- tolerated, and showed mainly P related adverse events. A phase III study is planned to confirm a role for P + S in metastatic melanoma. [Table: see text]

A phase III trial of nab-paclitaxel versus dacarbazine in chemotherapy-naive patients (pts) with metastatic melanoma: Analysis of peripheral neuropathy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20025-e20025
Author(s):  
Michele Del Vecchio ◽  
Evan Hersh ◽  
Michael Paul Brown ◽  
Arthur Clements ◽  
Carmen Loquai ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Metastatic Melanoma ◽  
Median Time ◽  
Performance Status ◽  
Stage Iv ◽  
Phase Iii ◽  
Common Side Effect ◽  
Ecog Performance Status ◽  
Phase Iii Trial ◽  
Grade 3

e20025 Background: Peripheral neuropathy (PN) is a common side effect associated with taxane treatment. In a phase III trial, nab-paclitaxel vs dacarbazine demonstrated a significant improvement in progression-free survival (4.8 vs 2.5 months; P = 0.044) and at the interim survival analysis, a trend toward prolonged overall survival (12.8 vs 10.7 months; P = 0.094) for the treatment of chemotherapy-naive patients with metastatic melanoma. Here we report on the PN profile of nab-paclitaxel in this phase III trial. Methods: Pts (median age, 63 years) with chemotherapy-naive stage IV melanoma (M1c stage, 65%; elevated LDH, 28%) and an ECOG performance status 0-1 were randomized to nab-paclitaxel 150 mg/m2 on days 1, 8, and 15 of a 28-day cycle (n = 264) or dacarbazine 1000 mg/m2on day 1 of each 21-day cycle (n = 265). PN events were defined based on the Standardized MedDRA Query (V 12.1, broad scope). Results: As expected, a higher proportion of pts receiving nab-paclitaxel vs dacarbazine had ≥ 1 treatment-related PN event (68% vs 8%; P < 0.001). Treatment-related grade ≥ 3 PN was more frequent with nab-paclitaxel vs dacarbazine (25% vs 0%; P < 0.001); 2 grade 4 events were reported in the nab-paclitaxel arm. Treatment-related grade ≥ 3 PN was 15% in pts who received up to the median of 3 cycles of nab-paclitaxel. PN led to dose reduction in 13% or discontinuation in 15% of nab-paclitaxel–treated pts. The median time to onset of grade ≥ 3 PN was 101 days (95% CI, 85 - 113). Most early-onset PN events, occurring within the first 3 cycles, were grade 1. Grade ≥ 2 PN events peaked by cycle 4 and subsided by cycle 9. Forty-one of the 64 (64%) pts with a grade ≥ 3 PN event had an improvement of ≥ 1 grade, with a median time to improvement of 28 days (95% CI, 17 - 64), and 33 of 64 (52%) pts had improved to grade 1 or better by a median of 67 days from onset (95% CI, 22- upper limit not estimable); 30 of 64 (47%) pts resumed treatment with nab-paclitaxel. Conclusions: In this phase III trial, grade ≥ 3 PN was the main treatment-related toxicity with nab-paclitaxel as observed in other studies. However, PN was rapidly reversible; a majority of pts had improvement of PN symptoms within 1 month and resumed treatment. Clinical trial information: NCT00864253.

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