Open-label prospective study of safety and efficacy of glass-based Y-90 radioembolization for infiltrative HCC with PVT.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 276-276
Author(s):  
Nima Kokabi ◽  
Juan C. Camacho ◽  
Minzhi Xing ◽  
John S. Kauh ◽  
Bassel F. El-Rayes ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Liver Toxicity ◽  
Univariate Analysis ◽  
Evaluation Criteria ◽  
Best Supportive Care ◽  
Open Label ◽  
Safety And Efficacy ◽  
Vein Thrombosis ◽  
Grade 3 ◽  
Bilirubin Toxicity

276 Background: Safety and efficacy of Yttrium-90 (Y90) therapy for infiltrative unresectable hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) require further evaluation. Methods: A prospective single center, open-label, single arm safety and efficacy study recruited patients with unresectable (Barcelona Liver Cancer Stage C) infiltrative HCC with PVT. Safety was assessed according to Common Terminology Criteria for Adverse Events v.3.0 at 1 week and monthly thereafter for 6 months post therapy. Efficacy was assessed by overall survival (OS) as primary endpoint. Tumor response was assessed by dynamic contrast MRI according to Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST at 1, 3, and 6 months (secondary endpoint). To achieve 0.95 power (α=0.05) and predicting prolongation of mean OS by at least 50% over the best supportive care (4 months ± 2 months (SD)), the study was designed to recruit 30 patients. Survival analysis was performed using Kaplan-Meier estimation. Prognostic factors were tested using log-rank and univariate analysis. Results: Thirty (n=30) patients were enrolled and underwent Y90 therapy (median age 63). The median OS was 13 months (CI: 4.1-21.1 months). Six patients had transaminitis (70% grade 1, 30% grade 2) while 8 patients had biliary toxicity (50% grade 1, 10% grade 2, 40% grade 3). Grade 3 bilirubin toxicity occurred in the same 2 patients with grade 2 transaminase toxicity. Although all patients recovered from transient liver toxicities, grade ≥2 liver toxicity was found to be predictor of poor outcome with median OS of 3.6 months for patients with grade ≥2 toxicity vs. 13 months for those with grade 1 or no toxicity (p=0.004). Child-Pugh class B, INR ≥1.5, and grade ≥2 hepatobiliary toxicities were found to be poor prognostic factors by both log-rank and univariate analysis (p<0.05). Upon short-term imaging follow up (mean 34 days post Y90), 80% of patients were found to have complete (13%) or partial (67%) response according to targeted mRECIST criteria, with 93% stable disease according to targeted RECIST. Conclusions: In patients with unresectable infiltrative HCC and PVT, Y90 therapy is a viable and safe treatment option.

scholarly journals Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8

2020 ◽  
Vol 8 (2) ◽  
pp. e001378
Author(s):  
Markus Hecht ◽  
Antoniu Oreste Gostian ◽  
Markus Eckstein ◽  
Sandra Rutzner ◽  
Jens von der Grün ◽  
...  
Keyword(s):  
Cell Density ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Induction Treatment ◽  
Single Cycle ◽  
Safety And Efficacy ◽  
Cd8 Cells ◽  
Programmed Death ◽  
Cd8 Cell ◽  
Grade 3

BackgroundTo determine safety and efficacy of single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab in stage III-IVB head and neck cancer.MethodsPatients received a single cycle of cisplatin 30 mg/m² on days 1–3 and docetaxel 75 mg/m² on day 1 combined with durvalumab 1500 mg fix dose on day 5 and tremelimumab 75 mg fix dose on day 5. Patients with pathologic complete response (pCR) in the rebiopsy after induction treatment or at least 20% increase of intratumoral CD8+ cell density in the rebiopsy compared with baseline entered radioimmunotherapy with concomitant durvalumab/tremelimumab. The objective of this interim analysis was to analyze safety and efficacy of the chemoimmunotherapy-induction treatment before radioimmunotherapy.ResultsA total of 57 patients were enrolled, 56 were treated. Median pretreatment intratumoral CD8+ cell density was 342 cells/mm². After induction treatment, 27 patients (48%) had a pCR in the rebiopsy and further 25 patients (45%) had a relevant increase of intratumoral CD8+ cells (median increase by a factor of 3.0). Adverse event (AE) grade 3–4 appeared in 38 patients (68%) and mainly consisted of leukopenia (43%) and infections (29%). Six patients (11%) developed grade 3–4 immune-related AE. Univariate analysis computed p16 positivity, programmed death ligand 1 immune cell area and intratumoral CD8+ cell density as predictors of pCR. On multivariable analysis, intratumoral CD8+ cell density predicted pCR independently (OR 1.0012 per cell/mm², 95% CI 1.0001 to 1.0022, p=0.016). In peripheral blood CD8+ cells, the coexpression of programmed death protein 1 significantly increased especially in patients with pCR.ConclusionsSingle cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab is feasible and achieves a high biopsy-proven pCR rate.

A Phase 1/2 Multi-Center, Randomized, Open Label Dose Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Efficacy of Pomalidomide Alone or in Combination with Low-Dose Dexamethasone in Patients with Relapsed and Refractory Multiple Myeloma Who Have Received Prior Treatment That Includes Lenalidomide and Bortezomib.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 301-301 ◽  
Author(s):  
Paul Richardson ◽  
David Siegel ◽  
Rachid Baz ◽  
Susan L. Kelley ◽  
Nikhil C. Munshi ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Maximum Tolerated Dose ◽  
Open Label ◽  
Advisory Committees ◽  
Dose Escalation Study ◽  
Safety And Efficacy ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Dose Dependent Increase

Abstract Abstract 301 Background: Pomalidomide (POM) is an IMiD® derived from thalidomide with a modified chemical structure with improved potency in vitro and potential efficacy and safety benefits in vivo. Two phase (Ph) 1b, single-center, ascending dose, open-label studies in pts with relapsed/refractory multiple myeloma (MM; Schey et al, 2004, Streetly et al, 2008) identified maximum tolerated dose (MTD) as 2mg QD or 5mg on alternate days (28 of each 28-day cycle). High response rates of POM alone in heavily pretreated pts were encouraging. To evaluate the MTD, safety and efficacy of POM alone or with Dexamathasone (dex) on a 21/28 day schedule, a Ph 1/2, multicenter, randomized, open-label, 3×3 dose-escalation study was initiated in pts with relapsed/refractory MM after at least 2 prior regimens, including bortezomib and lenalidomide. Methods: The study has a Ph 1 POM MTD (n=32) portion, followed by Ph 2 open-label randomized POM+ dex vs POM alone (192 pts planned). Eligible pts had documented relapsed/refractory MM. All pts received low-dose prophylactic aspirin QD and monitored for venous thromboembolic events (VTE). In Ph 1, POM was given QD on Days 1–21 of 28-day cycle: 4 dose levels of POM (2, 3, 4, 5mg) were studied with option to add dex at 40 mg/wk after 4 cycles for lack of response or progressive disease (PD). Pts enrolled in Ph 1 and discontinued either for intolerance or PD could not be enrolled in Ph 2. Toxicities and responses were assessed using CTCAE v3 and modified European Group for Blood and Marrow Transplantation (EBMT) criteria. Results: Results from Ph 1 of the study are reported with 32 pts enrolled to date. Fifteen pts discontinued therapy and 17 pts are ongoing for both safety and efficacy analyses. Mean age is 66.6 yrs (range 38–84), with median number of prior regimens 7 (range 2–18). MTD has not yet been reached. There were 4 dose reductions due to POM (5mg [2-neutropenia, 1-rash]; 3mg [1-neutropenia]) after 108 completed cycles. Neutropenia and thrombocytopenia were the most common grade 3/4 toxicities, with no dose-dependent increase apparent so far: 12 serious adverse events (SAEs) occurred in 10 pts; drug related events included POM (VTE, syncope, 3rd degree AV block, asthenia, diarrhea, neutropenia, anemia, rash); dex (lung infection with neutropenia); POM + dex (sepsis with pharyngeal abscess). AEs such as somnolence (1) VTE (1) neuropathy (2), and constipation (4) were uncommon. There were 3 deaths on study not attributed to POM; 2 pts died of rapid PD, 1 pt died of gastrointestinal perforation due to amyloidosis. Responses were seen at each dose level (Table 1). In 20/21 (95%) evaluable pts, clinical activity (SD or better) was reported. During treatment with POM alone, overall response rate (ORR; 1 CR, 2 PR, 5 MR) was 38% (8/21), mean duration of response (DOR) was 11.1 (range 4–32) wks, mean time to progression (TTP) was 8.3 (range 2–36) wks. Median completed cycles of POM +/− dex overall was 4 (range 1–12), with 13/21 evaluable pts (62%) having dex added to their regimens at various different cycles (median cycle 3, range 2–9) for PD or lack of response. During treatment with POM+dex, ORR (2 PR, 3 MR) was 38%, mean DOR of 14.2 (range 4–32) wks, and mean TTP of 20 (range 4–52) wks. In addition, there were 9 stable diseases (SD) on POM alone with mean DOR of 7.1 (range 4–16) wks, and 6 SD on POM + dex with mean DOR of 10.7 (range 8–16) wks. In 5/13 pts (38%), responses improved after dex was added (2 PR, 2 MR, 1 SD). Conclusions: These preliminary results indicate that POM alone or in combination with dex is associated with 38% MR or better, while SD was achieved in 43% (POM alone) and 46% (POM + dex), amongst heavily pretreated pts with relapsed/refractory MM. The incidence of SAEs and discontinuations decreased with increased dose of POM with no dose-dependent increase in grade 3/4 hematological toxicities. The MTD has not been reached to date. Overall, these data indicate that POM has an acceptable safety profile and is a clinically active therapeutic option for advanced refractory MM, warranting further investigation in this patient population. Disclosures: Richardson: Gentium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Keryx Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Millenium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Pomalidomide is an anti-proliferative and immunomodulatory agent that is in clinical development for relapsed/refractory MM. Siegel:Celgene: Speakers Bureau; Millenium Pharmaceuticals: Speakers Bureau. Baz:Celgene: Research Funding. Munshi:Novartis Pharmaceuticals: Consultancy, Speakers Bureau; Millenium Pharmaceuticals: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Sullivan:Merck: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Merrion: Membership on an entity's Board of Directors or advisory committees. Doss:Celgene: Speakers Bureau. Larkins:Celgene: Employment, Equity Ownership. Jacques:Celgene: Employment. Donaldson:Celgene: Employment. Anderson:Celgene: Consultancy, Honoraria, Speakers Bureau; Millenium Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau.

Multicenter Analysis of Elderly Hodgkin Lymphoma (eHL): Outcomes and Prognostic Factors in the Modern Era

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2625-2625 ◽  
Author(s):  
Andrew M. Evens ◽  
Irene Helenowski ◽  
Chadi Nabhan ◽  
Erika Ramsdale ◽  
June M McKoy ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Model ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
Stage Iii ◽  
Geriatric Syndrome ◽  
Cart Analysis ◽  
Multicenter Analysis ◽  
Grade 3 ◽  
Modern Era

Abstract Abstract 2625 Purpose. Survival rates for eHL (most commonly defined as age over 60 years) are significantly and disproportionately inferior to those achieved in younger patients (pts). Reported 5-year event-free survival (EFS) rates for advanced-stage eHL have historically ranged from 30%–45% with 5-year overall survival (OS) rates of 40%–55%. Potential explanations for these discrepant inferior outcomes include co-morbidities precluding delivery of chemotherapy, treatment-related toxicities, and biology of disease. Data examining toxicity, survival, and prognostication for eHL in the modern era are lacking. Methods. We report a multicenter collaboration that retrospectively investigated a large cohort of eHL pts treated over a recent 12-year period (June 1999 December 2010). We examined clinical characteristics, treatment-related toxicities, and outcomes. Furthermore, comorbidities were assessed using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) scale. Patients were also classified as “fit” vs “not fit” (i.e., loss of activities of daily living (ADLs), >3 grade 3 CIRS-G, any grade 4, and/or presence of geriatric syndrome). Univariate associations with survival were determined, while a multivariate Cox proportional hazards model was completed. Additionally, a prognostic model was constructed by classification and regression tree (CART) analysis. Results. 113 eligible pts were identified, while 95 had full data and were analyzed. Among these 95 pts (58M:37F), median age was 67 years (range, 60–89), with 33% of pts ages 70–79 years, while 7% were 80–89 years. 27% of pts had a prior malignancy at a median of 8.4 years (range, 1–25 years) prior to HL diagnosis, for which most had received radiation. At HL diagnosis, there were presence of B symptoms in 54%, performance status 2–4 in 27%, 21% with history of coronary artery disease, and 16% had diabetes. In terms of functional status, 61% of pts had a CIRS-G grade 3 or 4 in at least 1 category, while 46% had a cumulative score >6. Further, 17% had presence of a geriatric syndrome, 26% were classified as 'not fit', and 13% had loss of ADLs at time of HL diagnosis. 25% of pts had bone marrow involvement, while 20% had other extranodal disease (most common: bone and lung). Altogether, 64% of pts had stage III/IV disease, of which 58% had an international prognostic score (IPS) of 4–7. HL histology was nodular sclerosis in 47%, mixed cellularity 31%, NOS 16%, lymphocyte predominant 5%, and lymphocyte depleted 1%. Primary treatment consisted of: ABVD-based (n=67), MOPP-based (n=6), BCVPP (n=6), ChlVPP (n=5), radiation alone (n=4), CHOP (n=3), hospice (n=2), BEACOPP (n=1), and watchful waiting (n=1). 78% of pts received granulocyte-colony stimulating factor (G-CSF) with therapy. The overall response rate (ORR) among treated pts was 85% (73% complete remission (CR) rate). In terms of toxicity, the incidence of bleomycin lung toxicity (BLT) was 32%, which had an associated mortality rate of 25%. Notably, the incidence of BLT was 37% vs 0% among pts who received G-CSF vs not, respectively (p=0.041). With a median follow-up of 66 months (6–154) months, the 5-year EFS and OS for all eHL pts were 44% and 58%, respectively (stage I/II: 61% and 79%; and stage III/IV: 36% and 46%; p=0.009 and p=0.001, respectively). Prognostic factors that predicted survival on univariate analysis are detailed in Table 1. On multivariate regression analysis, 2 factors were associated with inferior survival: 1) age ≥ 70 years (EFS: 1.76 (95%CI 0.98–3.16), p=0.06; and OS: 2.24 (95%CI 1.16–4.33), p=0.02) and 2) Loss of ADLs (EFS: 2.47 (95%CI 0.98–6.21), p=0.055; and OS: 2.71 (95%CI 1.07–6.84), p=0.04). Furthermore, a survival model by multivariate CART analysis, based on number of these 2 adverse factors (0, 1, 2), was formed: 5-year EFS 73%, 51%, 0%, respectively (p<0.0001), and 5-year OS 93%, 68%, 11%, respectively (p<0.0001) (Figure 1). Conclusions. This large, retrospective multicenter analysis of eHL found a high ORR and CR rate, but poor long-term outcomes. As shown previously, a significant percentage of eHL pts suffered BLT, which was fatal in 25% and appeared strongly related to use of growth factors. Further, several geriatric specific variables, including loss of ADL's, was highly predictive of outcome and should be prospectively incorporated into clinical trials. Finally, we developed a new prognostic model for eHL that identifies pt populations with markedly divergent outcomes. Disclosures: No relevant conflicts of interest to declare.

Safety and pharmacokinetics (PK) of AMG 706 in combination with gemcitabine for the treatment of patients (pts) with solid tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14005-14005 ◽  
Author(s):  
T. J. Price ◽  
L. Lipton ◽  
J. Williams ◽  
J. McGreivy ◽  
S. McCoy ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Open Label ◽  
Multikinase Inhibitor ◽  
Vein Thrombosis ◽  
Finding Study ◽  
Label Dose ◽  
Grade 3 ◽  
Deep Vein

14005 Background: AMG 706 is an oral, investigational multikinase inhibitor (MKI) with antiangiogenic and direct antitumor activity achieved by selectively targeting VEGF, PDGF and Kit receptors. Methods: This is a fully enrolled, phase 1b, open-label, dose- finding study. The objectives are to determine the maximum tolerated dose and to assess safety and PK of AMG 706 in pts with solid tumors receiving AMG 706 plus gemcitabine. Pts =18 years with ECOG 0–2 and no prior treatment with bevacizumab or VEGFr MKIs were assigned to cohorts receiving escalating doses of AMG 706 (50mg QD, 125mg QD or 75mg BID continuously from day 2 of cycle 1) plus gemcitabine (1000mg/m2 weekly for 7/8 wks, then 3/4 wks per cycle) for up to 11 cycles. Assessments include dose-limiting toxicities (DLT) (weeks 1–4) and tumor response (every 3 months). Results: 26 pts were enrolled and received at least 1 dose of AMG 706 (50mg QD n=11; 125mg QD n=6; 75mg BID n=9). All but 2 pts have completed the study. Median (range) age was 57 (25–77) yrs. 65% of pts received prior chemotherapy; 4 pts received prior gemcitabine (50mg QD n=2; 125mg QD n=1; 75mg BID n=1). There were 2 DLTs: grade 4 neutropenia (125mg QD), grade 3 deep vein thrombosis (75mg BID). Treatment-related adverse events (AE) occurring in = 10% of pts are shown in the table . The mean AMG 706 PK profiles were not markedly different when AMG 706 was dosed on the same day or 24 hours after gemcitabine administration. Objective tumor responses per RECIST for 26 evaluable pts were: 2 unconfirmed PR (50mg QD n=1; 125mg QD n=1), 7 SD (50mg QD n=3; 125mg QD n=1; 75mg BID n=3), 11 PD (50mg QD n=7; 125mg QD n=3; 75mg BID n=1), and 6 not available (125mg QD n=1; 75mg BID n=5). Conclusions: These preliminary data suggest that, in pts with solid tumors, AMG 706 combined with gemcitabine had an expected AE profile at the target once-daily dose of 125mg QD, with little effect on AMG 706 PK. The data provide a foundation for conducting further trials, potentially including biliary tumors. Final data will be presented. [Table: see text] No significant financial relationships to disclose.

Safety and early efficacy results from a phase I study of volociximab (V) in combination with carboplatin (C) and paclitaxel (P) in patients (pts) with advanced non small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13513-e13513
Author(s):  
B. Besse ◽  
S. Almokadem ◽  
D. Planchard ◽  
I. Chico ◽  
C. L. Tsao ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Arterial Occlusion ◽  
Maximum Tolerated Dose ◽  
Clinical Activity ◽  
Open Label ◽  
Dose Escalation Study ◽  
Vein Thrombosis ◽  
Label Dose ◽  
Grade 3 ◽  
Peripheral Arterial

e13513 Background: Volociximab is a chimeric monoclonal antibody that blocks fibronectin binding to α5β1 and induces apoptosis in proliferating endothelial cells. Its anti-angiogenic actions are independent of the VEGF pathway. This is the first clinical study of voloxicimab in patients with advanced NSCLC. Methods: This phase 1b multi-center open-label, dose-escalation study was designed to determine the maximum tolerated dose of V in combination with full doses of C (AUC=6mg/ml.min) P (200mg/m2) with cycles repeated every 3 wks for a maximum of 6 cycles followed by a maintenance treatment with V alone. Eligible pts had histologically confirmed untreated stage IIIb or IV NSCLC. In cohorts 1 and 2, pts received V at 10 mg/kg and 20mg/kg IV, respectively, on days 1 and 8, of the first 21 day cycle then every 21 days. In cohort 3, pts received V 30 mg/kg IV every 21 days from day 1. We present here the interim safety analysis and RECIST response data of the combination therapy. Results: A total of 22 patients (9, 6 and 7 in cohorts 1, 2 and 3 respectively) who received at least one dose of treatment constitute the safety population. Reported salient adverse events (any grade) were constipation (68%), asthenia (64%), nausea (59%), arthralgia (55%) and paresthesia (46%). Grade 3 bowel obstruction in one patient was considered a DLT in cohort 2. No DLT's were observed in cohort 3. Seven pts reported at least one serious adverse event (all Grade 3) including deep vein thrombosis (1), peripheral arterial occlusion (1), proteinuria (1), pneumonitis (1), small intestinal obstruction (1), pleural effusion (1), hypoxia (1), dehydration (1) and orthostatic hypotension (1). Partial response was seen in 6 pts and stable disease in 12 out of 18 pts who were evaluable for response by RECIST. Conclusions: The highest dose of V tested (30 mg/kg q3w) in combination with CP appears well tolerated and the regimen has promising clinical activity in advanced NSCLC. [Table: see text]

Safety and efficacy of AMG 386 in combination with sunitinib in patients with metastatic renal cell carcinoma (mRCC) in an open-label multicenter phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4606-4606 ◽  
Author(s):  
Michael B. Atkins ◽  
Alain Ravaud ◽  
Gwenaelle Gravis ◽  
Kazimierz Drosik ◽  
Tomasz Demkow ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Angiogenesis Inhibitors ◽  
Risk Scores ◽  
Open Label ◽  
Safety And Efficacy ◽  
Kaplan Meier ◽  
Amg 386 ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Dose Modifications

4606 Background: AMG 386, an investigational peptide-Fc fusion protein, inhibits angiogenesis by disrupting the angiopoietin/Tie2 axis. We evaluated the safety and efficacy of AMG 386 plus sunitinib in patients (pts) with mRCC. Methods: Adults with mRCC who were naïve to angiogenesis inhibitors were sequentially enrolled to 2 cohorts: sunitinib 50 mg PO QD (4 wks on, 2 wks off) plus AMG 386 at 10 mg/kg (A) or 15 mg/kg (B) IV QW. Primary endpoints: adverse events (AEs), dose interruptions/reductions due to AEs in the first 12 wks of treatment; secondary endpoints included: progression-free survival (PFS) and response rate (ORR). Results: 85 pts received ≥1 dose of study medication (A/B, n=43/42). In A/B, 88%/76% were male and 30%/36% were age ≥65; MSKCC risk scores were low (40%/36%) or intermediate (60%/62%). For A/B: median follow-up time was 19.6/12.0 mos; AMG 386 discontinuations due to AEs were 16%/29%; and grade ≥3 treatment-related AEs occurred in 72%/74% with virtually all attributed to sunitinib. Grade 3 AEs occurring with >5% frequency were hypertension, hand foot syndrome, asthenia, fatigue, elevated lipase, diarrhea, mucositis, vomiting, thrombocytopenia, and neutropenia, with no distinction between dose levels. The percentage of pts with sunitinib dose interruptions within the first 12 wks (A/B, 58%/57%) met the prespecified criteria. One pt in B had fatal acute pulmonary edema. No pt developed anti-AMG 386 antibodies. The Kaplan-Meier estimate (95% CI) of PFS was 13.9 (10.4, 19.2) mos in A; PFS in B is not yet mature with only 21% of pts having disease progression. ORR (95% CI) was 58% (42, 73) in A including 1 CR, and 59% (42, 74) in B. Conclusions: In pts with mRCC, AMG 386 at 10 and 15 mg/kg combined with sunitinib appeared to be tolerable. Reported sunitinib dose modifications for the observation period were within the prespecified range. Efficacy results suggest potential benefit for the addition of AMG 386 to sunitinib.

Sorafenib (S) in patients (pts) with advanced hepatocellular carcinoma (HCC): Safety and efficacy in Child-Pugh (CP) class A and B patients.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 306-306
Author(s):  
Tiziana Pressiani ◽  
Corrado Boni ◽  
Lorenza Rimassa ◽  
Roberto Labianca ◽  
Stefano Fagiuoli ◽  
...  
Keyword(s):  
Descriptive Analysis ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Safety And Efficacy ◽  
Advanced Hcc ◽  
Class A ◽  
Tolerability Data ◽  
Prospective Trials ◽  
Open Label Trial ◽  
Grade 3

306 Background: S is the first systemic agent that has been shown to prolong survival in pts with CP A advanced HCC. However, its safety and efficacy have not been extensively evaluated in pts with CP B cirrhosis. Methods: We performed a descriptive analysis on pts with histologically documented advanced HCC and CP A/B cirrhosis, enrolled in a multicenter phase II randomized, open-label trial (data reported elsewhere), in order to assess the feasibility and efficacy of treatment with S in CP B pts. Written informed consent was obtained from all pts. Results: From April 2007 to July 2008, 297 pts were prospectively treated with S 400 mg bid, 234 (78.8%) CP A, 63 (21.2%) CP B. 232 pts were male (76%), median age was 68.3 yrs (range 19.8-89.2 yrs), 217 pts had no extra hepatic disease (73.1%). The two subgroups, according to CP class A or B, were homogeneous for all considered parameters. Median treatment duration was >3 months (mos) for 59.4% of CP A pts and for 27% of CP B pts (p <0.001). Median PFS for the total population was 3.9 mos, 4.3 mos for CP A pts and 2.1 mos for CP B pts (p<0.001). Median OS was 10 mos for CP A pts and 3.8 mos for CP B pts (p<0.001). Adverse events (all grades) were similar in type and incidence for CP A and B pts, with fatigue, stomatitis, diarrhea and weight loss having the highest incidence (44%, 41%, 38% and 38%, respectively). Specifically, no differences in terms of grade 3-4 events have been documented between the two groups. Conclusions: This study supports the feasibility of S also in advanced HCC pts with CP B status. Tolerability data suggest that pts with CP B status might potentially be treated safely with S for its potential survival benefits. Further prospective trials, specifically designed to investigate S in CP B pts, are eagerly advocated.

Long-term safety and efficacy of pomalidomide (POM) with or without low-dose dexamethasone (LoDEX) in relapsed and refractory multiple myeloma (RRMM) patients enrolled in the MM-002 phase II trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8588-8588 ◽  
Author(s):  
David Samuel DiCapua Siegel ◽  
Paul Gerard Guy Richardson ◽  
Ravi Vij ◽  
Craig C. Hofmeister ◽  
Rachid C. Baz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Response Duration ◽  
Median Number ◽  
Open Label ◽  
Safety And Efficacy ◽  
Vein Thrombosis ◽  
Intent To Treat

8588 Background: MM-002 is a randomized, open-label, multicenter phase II trial evaluating the safety and efficacy of POM with or without LoDEX in advanced RRMM pts. Methods: Pts who had received ≥ 2 prior therapies, including lenalidomide (LEN) and bortezomib (BORT), and were refractory to their last treatment were randomized to POM+LoDEX (POM 4 mg/day, days 1–21 of a 28-day cycle; LoDEX 40 mg/week) or POM alone. End points included progression-free survival (PFS), response rate (according to EBMT criteria and investigator assessment), response duration, overall survival (OS), and safety. The efficacy outcomes are based on the intent-to-treat population (POM+LoDEX, n = 113; POM, n = 108). Results: The median number of prior therapies in each group was 5 (range 1–13). In the POM+LoDEX arm, 30 (27%) pts had high-risk cytogenetics, including del(17p13) and/or t(4p16/14q32). The overall response rate (≥ partial response) was 34% and 15% with POM+LoDEX and POM, respectively, with a median duration of 8.3 (95% CI: 5.8–10.1) and 8.8 (95% CI: 5.5–11.4) mos, respectively. At least minimal response was observed in 45% and 31% of pts, respectively. Median PFS was 4.6 (95% CI: 3.6–5.5) and 2.6 (95% CI: 1.9–2.8) mos with POM+LoDEX and POM, respectively, with a median follow-up of 16.0 and 12.2 mos. Median OS was 16.5 (95% CI: 12.4–18.5) and 13.6 (95% CI: 9.6–18.1) mos, respectively. The most common treatment emergent Gr 3/4 adverse events (AEs) reported in the safety population (n = 219) were neutropenia (44%), anemia (23%), thrombocytopenia (21%), and pneumonia (18%); there were no reports of Gr 3/4 peripheral neuropathy. The incidence of deep-vein thrombosis was low (2%). AEs were managed through dose reductions or interruptions, and supportive care with G-CSF (52%), RBC transfusions (47%), and platelet transfusions (17%). Discontinuations due to AEs were 10%. Conclusions: POM with or without LoDEX is clinically effective and generally well tolerated in RRMM pts who have received multiple prior treatments, including LEN and BORT. AEs were predictable and manageable. Updated data will be presented at the meeting. Clinical trial information: NCT00833833.

Evaluation of liver toxicity using Child-Pugh, MELD, and MELD-Na following stereotactic body radiation therapy (SBRT) of hepatocellular carcinomas.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 365-365
Author(s):  
Louis Lu ◽  
Eman ElAlfy ◽  
Daniel Wahl ◽  
Matthew H. Stenmark ◽  
Theodore Steven Lawrence ◽  
...  
Keyword(s):  
Time Course ◽  
Liver Toxicity ◽  
Background Radiation ◽  
Univariate Analysis ◽  
Vein Thrombosis ◽  
Point Increase ◽  
Chi Squared ◽  
Radiation Induced ◽  
The University ◽  
Hep B

365 Background: Radiation-induced liver disease (RILD) has been tracked when assessing the safety of fractionated liver radiotherapy. However, due to the rarity and severity of events, a more sensitive measure of liver damage is necessary. This study characterizes the time course of changes in generalizable measures of liver function as potential toxicity metrics. Methods: In this IRB-approved retrospective study, the records of 63 patients with 87 HCC tumors treated with SBRT at the University of Michigan between 2006 and 2012 were reviewed. Changes in Child-Pugh (CP), MELD, and MELD-Na were analyzed using the Student t test and chi-squared test. Results: 83% of the patients had cirrhosis, 62% hepatitis (hep) C, 7% hep B, 25% alcoholic, and 13% other. 83% had prior liver-directed therapy. 24% had >1 tumor concurrently treated with SBRT. Median tumor size was 2.3 cm (0.7-10), gross tumor volume was 9.2 cc (0.6-469), and mean liver dose-GTV was 4.4 Gy (0-17.6 Gy). Prior to SBRT, 73% were CP A, 25% CP B, and 2% CP C. Median baseline CP, MELD, and MELD-Na were 5, 9, and 10. Mean CP increases after 3, 6, 9, and 12 months were 0.84, 1.79, 1.72, and 1.33; increases in MELD 1.47, 2.88, 5.38, and 3.91; increases in MELD-Na 1.45, 2.03, 4.24, and 2.48. All changes were significantly increased from baseline. On univariate analysis, >1 tumor and cirrhosis predicted for a 1+ point increase in CP and >1 tumor and higher mean liver dose-GTV for a 2+ point increase in CP. Older age, >1 tumor, smaller GTV, and smaller max tumor dimension predicted for a 10+ point increase in MELD and >1 tumor, hep C cirrhosis, and higher baseline MELD-Na for MELD-Na. Patients treated concurrently to >1 tumor had greater increases in CP (3.60 vs. 0.81), MELD (9.33 vs. 1.97), and MELD-Na (8.47 vs. 2.19), p < 0.0001 for all, compared to those with 1 tumor. No differences were seen with gender, portal vein thrombosis, number of prior treatments and baseline Child-Pugh classifications. Conclusions: We describe a time course and predictive factors for change in CP, MELD, and MELD-Na scores after SBRT for HCCs. These should be investigated further for potential use in toxicity modeling after incorporating dosimetric parameters.

Impact of gender on multikinase inhibitors (MKIs) toxicity in patients (pts) with advanced pancreatic and gastrointestinal neuroendocrine tumors (NETs): A pooled analysis of two phase II trials with pazopanib and lenvatinib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4109-4109
Author(s):  
Jorge Hernando-Cubero ◽  
Enrique Grande ◽  
Daniel E. Castellano ◽  
Toni Ibrahim ◽  
Nicola Fazio ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Liver Toxicity ◽  
Task Force ◽  
Pooled Analysis ◽  
Phase Ii Trials ◽  
Open Label ◽  
Two Phase ◽  
Phase Ii Studies ◽  
Grade 3

4109 Background: Retrospective data in some cancer types suggested a possible different toxicity profile with chemotherapy and targeted therapies according to gender. However, data from prospective studies are still very limited, especially in infrequent tumors such as NETs. Methods: Pts with advanced pancreatic and gastrointestinal NETs treated with pazopanib or lenvatinib in the multicenter open-label phase II studies PAZONET and TALENT respectively, were included in the analysis. Both studies were performed by Spanish Task Force Group for Neuroendocrine Tumors (GETNE). All toxicity grades with an incidence higher than 5% were considered for univariate review. Additionally, all grade 3-4 toxicities were analyzed separately. Results: 155 pts (47.7% female) with 1213 adverse events (AEs) (20% G3-4) divided in 121 categories were included. In female patients, liver toxicity, headache, pyrexia, nausea/vomiting, hair/skin disorders and dizziness were significantly more common (table). The only toxicity with higher incidence in men was dysphonia (OR 0.42, 95% CI 0.2-0.9, p 0.02). There were no gender differences in grade 3-4 toxicities. Conclusions: We observed significant differences in toxicity AEs by gender in two prospective phase II studies with MKIs in NETs patients. Potential different approach to manage toxicity may be adopted based on gender. [Table: see text]

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