Cetuximab in combination with docetaxel (T) in patients with operable, triple-negative breast cancer (TNBC): Preliminary results of a multicentre neoadjuvant pilot phase II study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1057-1057
Author(s):  
Jean Marc Nabholtz ◽  
Marie-Ange Mouret-Reynier ◽  
Isabelle Van-Praagh ◽  
Véronique Servent ◽  
Jean-Philippe Jacquin ◽  
...  
Keyword(s):  
Ductal Carcinoma ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Complete Response ◽  
Conservative Surgery ◽  
Median Number ◽  
Clinical Response Rate ◽  
Preliminary Results ◽  
Grade Ii ◽  
Grade Iii

1057 Background: Cetuximab is an antiboby targeting the epidermal growth factor receptor (EGFR) to which a role has been suggested in TNBC. Therefore, we evaluated the combination of docetaxel with cetuximab as neoadjuvant therapy of operable TNBC. Methods: 35 patients with stage II-IIIA disease were prospectively included in this multicentre pilot study. Systemic therapy (ST) consisted of 6 cycles of T (100 mg/m2) q.3 weeks, in combination with weekly cetuximab (first dose : 400mg/m², then : 250 mg/m²/week) for 6 cycles. All patients underwent surgery at completion of ST. Complete pathologic response (pCR) was the primary endpoint (Sataloff : J Am Coll Surg 1995 ; Chevallier : Am J Clin Oncol 1993), with toxicity and biologic ancillary studies as secondary endpoints. Results: Patients characterisctics are as follows : mean age 48 [28-67] ; T1 : 3%, T2 : 73%, T3 : 24% (mean tumor size : 40 mm [15-100]) ; N0 : 61% and N1-N2 : 39%; invasive ductal carcinoma : 100%; Scarff-Bloom-Richardson Grade III : 73%, grade II : 27%. The median number of cycles was : T : 6 [1-6], cetuximab : 15 [1-18]. Pathological complete response was 24% according to Chevallier and Sataloff’s classifications and 28% if we consider response in breast. Preliminary results on 23 patients show an overall clinical response rate of 57% (22% CR). Conservative surgery was performed in 75% of cases. Skin toxicity was the main side-effect : grade II : 39%, grade III : 36%, grade IV : 3%. Neutropenia grade IV : 12.7%, febrile neutropenia : 1.3%, infection : 0%. Hand-foot syndrome grade III : 3%, grade II : 3%. Ungueal toxicity grade III : 3%, grade II : 33%. Conclusions: These preliminary results suggest that cetuximab in combination with Tappears to have a modest efficacy in operable TNBC. Clinical trial information: NCT00600249.

Impact of biomarkers in predictivity of the efficacy and toxicity of a combination of panitumumab plus FEC 100 followed by docetaxel in a phase II neoadjuvant trial for triple-negative breast cancer (TNBC) patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1051-1051
Author(s):  
Jean-Marc A. Nabholtz ◽  
Marie-Melanie Dauplat ◽  
Catherine Abrial ◽  
Beatrice E. Weber ◽  
Marie-Ange Mouret-Reynier ◽  
...  
Keyword(s):  
Ductal Carcinoma ◽  
Skin Toxicity ◽  
Ki 67 ◽  
Cutaneous Toxicity ◽  
Before And After ◽  
Hand Foot Syndrome ◽  
Grade Ii ◽  
Cutaneous Toxicities ◽  
Grade Iii

1051 Background: We evaluated the combination of a standard chemotherapy with panitumumab as neoadjuvant therapy of operable TNBC. Complete pathologic response (pCR) was the primary endpoint, with toxicity and biologic ancillary studies as secondary endpoints. Methods: Sixty patients with stage II-IIIA disease were prospectively included in this multicentre pilot study. Systemic therapy (ST) consisted of 4 cycles of FEC 100 (500/100/500 mg/m2) q.3 weeks followed by 4 cycles of T (100 mg/m2) q.3 weeks, in combination with panitumumab (9 mg/kg) for 8 cycles q.3 weeks. All patients underwent surgery at completion of ST. Paraffin-embedded samples and frozen samples have been systematically realised before and after neaodjuvant treatment in order to evalutate the biological profile of the tumor. Patients characteristics are : median age 50 ; median tumor size : 40 mm ; invasive ductal carcinoma : 96% ; Scarff-Bloom-Richardson Grade III : 70%, grade II : 30%, ki-67-positive : 100%, EGFR-positive : 78%, cytokeratine5-6-positive : 48% and p53-positive : 59%. Pathological response showed a pCR according to Sataloff’s classification of 52.38% and according to Chevallier’s classification of 46.52%. Skin toxicity was the main side-effect : Cutaneous toxicity grade IV : 5%, grade III : 30%, grade II : 20%. Neutropenia grade IV : 27% ; febrile neutropenia : 5%. Infection : 0%. Hand-foot syndrome grade III : 3.3%. Ungueal toxicity grade III : 1.6%, grade II : 20%. Results: We have tested the predictive value of ki-67, EGFR, cytokeratine 5-6 and p53. Only ki-67 is predictive of a pCR according to Chevallier’s classification (p=0.026), with a cut-off of 40% of positive cells (ROC curve): 62% of pCR if ki-67> 40% versus 23% if not (relative risk : 2.7). Low EGFR, high p53, and high cytokeratine 5-6 tended to be associated with poor reponse. No correlations were found between cutaneous toxicities and these biomarkers. The cutaneous toxicities were not predictive. Conclusions: HighKi-67 is predictive of more pCR. High EGFR, low p53 and low cytokeratine 5-6 tended to be associated with better response, but the data are not significant.

Outcomes after Double Umbilical Cord Blood Transplantation in Children: A Survey on Behalf of Eurocord and PDWP-EBMT

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2570-2570
Author(s):  
Federica Giannotti ◽  
Annalisa Ruggeri ◽  
Gerard Michel ◽  
Jean-Hugues Dalle ◽  
Tracey O'Brien ◽  
...  
Keyword(s):  
Single Unit ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Median Number ◽  
Cell Dose ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Grade Iii

Abstract Double UCBT (dUCBT) has been used in adults to reach an acceptable cell dose. For most children a single unit with a total nucleated cell (TNC) dose >3x107/Kg can be easily identified, but that is not always the case for heavier patients (pts). Use of dUCBT might decrease relapse and increase graft-versus-host-disease (GvHD). Data on dUCBT in children are scarce in the literature. A recent randomized study in children has described similar outcomes after double compared to single UCBT. Our study provides an overview of the use of dUCBT in the pediatric population reported to Eurocord. We retrospectively analyzed the outcomes of unrelated dUCBT in 177 children transplanted between 2002 and 2012 in 61 EBMT centres. Analysis was performed separately for pts with malignant (n=139) and non-malignant (NM, n=38) diseases. Among pts with malignancies, 76 had ALL, 40 AML, 6 MDS, 2 CML, 11 NHL, 3 Hodgkin Lymphoma and 1 Multiple Myeloma. Median age at dUCBT was 15 years (1.3-17.9) and median weight was 55 kg (13-97). Disease status at dUCBT was 1st complete remission (CR) (36%), ≥2nd CR (34%) or advanced (25%), and missing in 5% of the pts. In this group, 117pts received a myeloablative conditioning (MAC) and 22 a reduced intensity regimen (RIC). Cyclophosphamide+fludarabine+TBI was administered to 41% of the pts; 55% received ATG in the conditioning. Median number of collected TNC was 5.7x107/kg (3,6-12,8). Considering the unit with the higher number of HLA incompatibilities with the recipient, 56% had 2 mismatches. GvHD prophylaxis was cyclosporine-A (CSA) based in 93% of the pts (58% received CSA + mycofenolate mofetil). Median follow-up was 31 months. Cumulative incidence (CI) of neutrophil (PMN) and platelet (PLT) engraftment was 88% at 60 days and 64% at 180 days after dUCBT, and it was achieved with a median time of 24 and 45 days, respectively. Among the 122 pts with PMN engraftment, 85/94 with available data on chimerism were full donor and, of these, 20% had dual chimerism. CI of acute GvHD grade II-IV and grade III-IV at 100 days was 51% and 26%, respectively; it was significantly higher in pts who did not receive ATG (grade II-IV: 35% vs 67%, p=0.004; grade III-IV: 12% vs 37%, p=0.0075). Chronic GvHD was observed in 24/104 pts at risk (60% extensive; 2-year (yr) CI: 18%). The 2-yr CI of relapse was 31%. In univariate analysis, RIC, advanced stage at transplantation and a collected TNC dose lower than the median, were significantly associated with higher rates of relapse.The 2-yr CI of transplant related mortality (TRM) was 27%. Overall, 73 pts died: 35 of relapse, 15 of infections, 9 of GvHD and 14 of other causes. The 2-yr disease free survival (DFS) and overall survival (OS) were 42% and 45%, respectively. Among pts with NM disorders, 24 had bone marrow failure syndrome (BMFS) (10 Fanconi Anemia, 13 Acquired Aplastic Anemia and 1 other inherited BMFS), 2 hemoglobinopathies, 7 immune deficiencies and 5 metabolic disorders. Median age at dUCBT was 11 years (0.7-17.9) and the median weight was 40 kg (13-70). In this group, 27 pts received a RIC (40% TBI based), 10 a MAC (90% busulfan based), and 1 no conditioning regimen. ATG was administered to 82% of the pts and GvHD prophylaxis was CSA-based in 77%. The median number of collected TNC was 8.4x107/kg (1,2-11,2) and 60% of the grafts had ≥2 HLA mismatches with the recipient. Median follow-up was 39 months. Overall, 28 pts achieved PMN engraftment and 16 PLT engraftment, with a median time of 23 and 61 days, respectively. In univariate analysis, pts with BMFS compared to others had a significantly lower CI of PMN engraftment (58% vs 100%, p=0.002). Among the 10 pts who did not engraft, 3 had autologous reconstitution and 3 had a subsequent allogeneic HSCT. Forteen pts developed acute GvHD grade II-IV and 10/25 pts at risk had chronic GvHD (3 extensive). Overall 21 pts died (17 with BMFS): 9 of infections, 5 of GvHD and 7 of other causes. The 2-yr OS was 42% and it was significantly lower in pts with BMFS compared to those affected by other NM disorders (28% vs 70%, p=0.03). In pts with malignancies, despite a higher incidence of acute GvHD, DFS and OS seem to be comparable to those reported in the literature for single UCBT or HSCT from other alternative stem cell sources. In the NM disorders group, despite the high cell dose, dUCBT did not seem to improve results in pts with BMFS. This survey suggests that dUCBT is feasible in children and should be considered when a single unit with an adequate cell dose is not available. Disclosures No relevant conflicts of interest to declare.

Dermatological toxicities of panitumumab in the treatment of patients with metastatic colorectal cancer (mCRC) from three clinical studies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14551-14551 ◽  
Author(s):  
D. A. Drelich ◽  
L. Rose ◽  
M. Ramirez ◽  
M. Jacobs ◽  
E. Mitchell
Keyword(s):  
African American ◽  
Clinical Studies ◽  
Human Monoclonal Antibody ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Metastatic Potential ◽  
Median Number ◽  
Egfr Expression

14551 Introduction: Epidermal growth factor receptor (EGFr) expression in CRC is associated with metastatic potential and poor prognosis. Panitumumab, a fully human monoclonal antibody against EGFr, was approved for the treatment of patients with refractory mCRC. The main side effects of panitumumab include dermatological manifestations that have been termed “rash”. However, classification of the dermatological manifestations has not been clearly described. Methods: We summarized the dermatological manifestations of 19 patients from 3 clinical studies investigating the the safety and efficacy of panitumumab monotherapy in mCRC in a single institution. Two of these studies were open lable, phase 2 in design which enrolled patients with documented disease progression (PD) during or after adequate doses of fluoropyrimidine, irinotecan, and oxaliplatin chemotherapy. In the other panitumumab was given in combination with irinotecan or oxaliplatin with bevacuzumab, 5FU, and leucovorin. Pts received panitumumab at 6mg/kg Q2W until PD or intolerability. Skin assessments were made q2w. Results: Five patients were men (26%) and 14 (73%) women; 12 were Caucasian (63%) and 7 (36%) African American. The median age was 53 (Range 38–80). Tumor response, disease control, and skin manifestations did not correlate with tumor EGFr levels as assessed by immunohisxtochemistry (Dako EGFR pharmDxtm). No enhancement of skin toxicity was observed when panitumumab was combined with chemotherapy. The median number of cycles received was 11 (Range 3–20). All pts experienced erythema; 17 macular/papular; 13 pustular; 18 acneiform rash; 15 pruritis; 3 honey crusting; 15 dry/flaking; 11 paronychia; 9 hirsuitism; 9 trichomegaly; and all 7 African American patients had significant hyperpigmentation. Photograph illustrations of each category and severity will be presented. Conclusion: Rash associated with panitumumab is common and can be classified according to the clinical dermatological manifestations; specific treatment strategies should be developed and evaluated accordingly. This is the first report of hirsuitism in women and hyperpigmentation in African Americans. [Table: see text]

Phase II study of neoadjuvant treatment with docetaxel, capecitabine, and trastuzumab in HER-2-positive locally advanced or inflammatory breast cancer: TXH trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11581-e11581
Author(s):  
G. Perez Manga ◽  
P. Khosravi-Shahi ◽  
Y. Izarzugaza Peron ◽  
A. Soria Lovelle ◽  
R. Gonzalez del Val ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Complete Response ◽  
Conservative Surgery ◽  
End Point ◽  
Her 2

e11581 Background: Preoperative chemotherapy(CT) with trastuzumab(H)improves pathologic complete responses(pCR) in patients(ps)with Her-2+locally advanced breast cancer(LABC). Methods: This is an unicenter phaseII trial of a new neoadjuvant CT with H(without anthracyclines)in Her-2+LABC.Primary end-point was pCR.Secondary endpoints were:clinical response rate(CRR);breast conservative surgery rate(BCSR);pathologic tumoral size(pTS);disease-free survival(DFS);overall survival(OS)and toxicity profile.Ps with histologically confirmed Her-2+LABC, PS ≤2, LVEF >50%,and adequate bone marrow, renal and hepatic function were eligible.Treatment:docetaxel(T)36 mg/m2IV d1,8 and 22;capecitabine(X)750 mg/m2/12h PO d1- 14;and H 4mg/kgIV 1ºd,followed by weekly 2mg/kg in a 4-week course repeated for up to 4cycles,followed by surgery.Ps received a maximum of 6 cycles,according to investigator criteria.Radiotherapy(RT)and hormonetherapy(Ht) were allowed after surgery.Expression of markers was determined by immunohistochemistry(IHC)before CT. Results: The trial was closed due to poor accrual on March 2008.N=16ps:median age=47years(30–68); premenopausal=69%; ductal carcinoma=94%; left side=37,5%; clinical(c)stage:IIA=6.2%,IIB=43.8%;IIIA=31.2%;IIIB=18.8%;c node+=50%; median c tumoral size= 5cm(2- 10);grade:G2=53%and G3=47%;ER+ =75%;PgR+=62.5%;RP+/RE+ =62.5%;EGFR negative =87.5%;p53+=37.5;median KI67=22.5%(2- 79%);Her2+ by IHC+++ =87.5%and IHC++/FISH+ =12.5%;RT= 50%;median dose=50Gy;Ht=75%;and all ps received adjuvant H. 1º End Point: Three ps(18.8%) had pCR in breast and nodes;4ps(25%)had pCR in primary site,and among ps with c node+ 37.5%(3ps)had pCR in nodes. 2º End-Points: 1)CRR=81.2%(complete response=25%;partial=56.2%;no response=18.8%);2)BCSR=6.2%;3)Median pTS=2cm(0–5cm);4)Safety:TXH is very well tolerated:dose delays=14%;dose reductions=7%;no p had a decreased LVEF after neoadjuvant CT.Three ps had decreased LVEF during adjuvant H(median=43%).5)Only 2 events had occurred.Survival data will be reported in the meeting. Conclusions: Neoadjuvant TXH is a new active regimen in Her- 2+LABC with a manageable toxicity profile. No significant financial relationships to disclose.

Nivolumab in renal cancer: French evaluation of use, current practices and medico economic approach.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16093-e16093
Author(s):  
Francoise Grude ◽  
Gildas Appéré ◽  
Fanny Marhuenda ◽  
Delphine Deniel Lagadec ◽  
Elouen Boughalem ◽  
...  
Keyword(s):  
Survival Data ◽  
Renal Carcinoma ◽  
Real Life ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Real Life Setting ◽  
Medico Economic ◽  
Ecog Ps ◽  
Grade Iii

e16093 Background: Since April 2016 (EMA approval), Nivolumab could be prescribed in advanced renal carcinoma after prior treatment. The Brittany and Pays de la Loire Cancer Observatory has collected data on their real-life indications, current management, safety, efficacy and medico-economics. Methods: All non opposing adult patients with renal carcinoma initiated nivolumab (3 mg/kg q2w) in 2016 and 2017 were included. Minimum follow-up for survival was 12 months. Sex, age, performans status PS ECOG, toxicities, response rate, Progression Free Survival (PFS) and Overall Survival (OS) have been studied. Results: 141 pts were treated by nivolumab in 2016 and 2017 with a median age of 68 years old [39-94] and with 26% aged at least 75 years. The median number of courses was 7 [1-47]. 68 pts (48%) had 1 to 6 courses, 16 pts (11%) 7 to 12 courses, 25 pts (18%) 13 to 24 courses and 32 pts (23%) more than 25 courses. 81 (58%) pts were treated in 2nd line, 34 (24%) in 3rd line, and 25 (18%) in further lines. All lines combined, Complete Response (CR) was observed for 3 pts (2%), Partial Response (PR) for 26 pts (18%), Stable Disease (SD) for 36 pts (26%) (disease control DC : 46%) and disease progression for 51 pts (36%). For 25 pts (18%), nivolumab treatment has been stopped before first medical imaging. PS ECOG was 0-1 for 88 pts (62%), 2 for 21pts (15%), 3-4 for 8 pts (6%) and unknown for 24 pts. Median OS and PFS were 18.2 months and 3.2 months, respectively. No difference on survival has been noticed according to gender, treatment line, age (cut-off 70 or 75 yo) and grade III/IV toxicity. However, OS and PFS were significantly influenced by general health (p < 0.0001). PFS for PS 0-1 pts was 6.5 months, for PS2 2.3 months and for PS3-4 0.8 months. OS was not reached for PS0-1 pts, 3.8 months for PS2 pts and 0.8 months for PS3-4 pts. OS for patients with DC (RC+RP+SD) has not reached and PFS was 14.9 months respectively. 17% of patients presented grade III/IV toxicities. Nivolumab courses during the 2 years costed 5.1 millions of euros (drug, hospitalisation and transportation). 80% of this costs were dedicated to pts who experienced DC. Conclusions: In real life setting, survival outcomes and toxicities with nivolumab in advanced renal carcinoma are comparable to literature’s data. ECOG PS≥2 pts presented shorter survival than PS0-1 pts. Interestingly, 80% of the cost incurred for these treatments benefited to pts with DC. Updated survival data will be available be shown at the meeting.

Outcome and evaluation of 1p and 19q deletion by chromogenic in situ hybridization (CISH) in patients with diagnosis of oligodendroglioma (OD) and oligoastrocitoma (OA).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21025-e21025
Author(s):  
Santiago Rafael Bella ◽  
Jose Roberto Llugdar ◽  
Alejo Lingua ◽  
Ricardo Alejandro Theaux ◽  
Francisco Papalini ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Tumor Tissue ◽  
Complete Response ◽  
Number Of Patients ◽  
Response To Chemotherapy ◽  
Pathological Evaluation ◽  
Grade Ii ◽  
Grade Iii

e21025 Background: In OD and OA, the 1p and 19q deletion has prognostic value in survival. It is also a predictive factor for response to chemotherapy. Fluorescence in situ hybridization (FISH) is the standard method for its evaluation. CISH could be an alternative that has already been validated in other neoplasias. In OD and OA, this combined deletion is present in about 50% of patients when analyzed with FISH. Methods: Patients resected at Clinica Reina Fabiola from january 2006 to january 2010 and diagnosed of OD and OA were propectivelly included. Paraffin-embebed tumor tissue was analyzed for 1p19q deletions by CISH. The results were correlated to the histology (OD and OA) and grade (II and III) of the tumors. Results: The demographic features of the patients from the present study coincide with literature. The 1p and 19q deletion was found in 3 of the 24 patients analyzed (13%). The combined deletion was only found in those with grade II OD. No combined deletion was found in patients diagnosed of grade III OD and grade II and III OA. In the subgroup of patients with grade II OD, the combined deletion was observed in 3 of 11 patients (27%). The 3 patients in which the deletion in both chromosomes was observed, received treatment with chemotherapy and radiotherapy, all of them with complete response. 5 years DFS was 90%-median follow up 36,8 (CI: 30,5-42,98) Conclusions: The detection of the combined deletion with CISH technique was inferior (13%) than the literature. We cannot demonstrate that CISH is a reliable method for the detection of the 1p and 19q deletion. The possible reasons of this difference could be attributed to the number of patients of the study, to deviations in the procedures of the test or to the fact that the CISH method is not coincident with FISH. This prospectivelly monoinstitutional results are also different to our previous report, and may be due to different pathological evaluation.

Excellent Long-Term Survival of Patients with Steroid-Refractory and Steroid-Dependent Acute Graft-Versus-Host Disease after Extracorporeal Photochemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1244-1244
Author(s):  
Hildegard T. Greinix ◽  
Robert M. Knobler ◽  
Nina Worel ◽  
Margit Mitterbauer ◽  
Axel Schulenburg ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Complete Response ◽  
Graft Versus Host ◽  
Steroid Dependent ◽  
Grade Ii ◽  
Grade Iii ◽  
Steroid Refractory ◽  
Acute Graft

Abstract Despite posttransplantation immunosuppressive therapy, acute graft-versus-host disease (GVHD) remains a major cause of sickness and death. Second-line therapies for steroid-refractory acute GVHD have been used with limited success. Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing agent 8-methoxypsoralen and UV-A radiation (ECP) has been shown to be effective in the treatment of selected diseases mediated by T cells. We have reviewed the responses and long-term outcome of 59 hematopoietic stem cell transplant (HSCT) patients treated from 1996 to 2003 with ECP for steroid-refractory acute GVHD, defined as progression or no improvement of acute GVHD after a minimum of 4 (range, 4–49, median 17) days of treatment with prednisone (n=37) or steroid-dependent acute GVHD, defined as flare-up of GVHD during prednisone taper (n=22). Patients received HSCT from 17 related and 42 unrelated donors. In 28 cases an HLA-mismatch between recipient and donor was present. Prior to ECP, grade III–IV GVHD was observed in 23 patients (39%) and grade II GVHD in 36 (61%). Organs involved included skin in 97% of patients, liver in 39%, and GI tract in 17%. Treatment consisted of ECP on two consecutive days per week (=1 cycle) for a median of 7 (range, 1–45) cycles administered within a median of 3 (range, 0.5–31) months in addition to cyclosporine A and prednisone. Three months after initiation of ECP complete resolution of GVHD was achieved in 82% of patients with cutaneous, 61% with liver, and 61% with gut involvement. Complete responses were obtained in 86% of patients with grade II, 55% of patients with grade III, and 30% of patients with grade IV acute GVHD. Probability of transplant-related mortality (TRM) at 4 years after HSCT is 15% in patients with complete response to ECP compared to 88% in patients not responding completely. After a median follow-up of 46 (range, 9–45) months since discontinuation of ECP, 28 (47%) patients are alive including 22 without chronic GVHD. Probability of survival (OS) at 4 years after HSCT is 59% in patients with complete response to ECP compared to 11% in patients not responding completely. Besides response to ECP only organ involvement and grade of GVHD at start of ECP, and ability to timely taper steroids during ECP had a significant impact on both TRM and OS. Thus, ECP is an effective adjunct therapy for acute steroid-refractory and steroid-dependent GVHD. Our long-term results demonstrate durability of responses without adverse events.

Intravenous (i.v.) Busulfan (Bu) Plus Melphalan (Mel) Is a Well-Tolerated Preparative Regimen for Stem Cell Transplantation (SCT) in Patients (pts) with Advanced Lymphoid Malignancies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2742-2742
Author(s):  
Partow Kebriaei ◽  
Timothy Madden ◽  
Neil Thapar ◽  
Elizabeth J. Shpall ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Median Time ◽  
Conditioning Regimen ◽  
Test Dose ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
Fixed Dose ◽  
High Dose ◽  
Lymphoid Malignancies ◽  
Grade Ii ◽  
Grade Iii

Abstract High dose chemotherapy and SCT is an accepted treatment option for pts with relapsed lymphoid malignancies. However, relapse remains a significant issue for pts with advanced disease. A double alkylating regimen of Bu and Mel has been suggested as an effective and myeloablative pre-transplant conditioning regimen. Historically, oral Bu was used and the combination resulted in considerable mucositis and VOD. Recently, an i.v. formulation of Bu has been developed that has less pharmacokinetic (PK) variability. We are investigating the safety and efficacy of i.v. Bu-Mel in pts with lymphoid malignancies undergoing auto- or allo-SCT. Patients and Methods: The conditioning regimen consists of i.v. Bu 130 mg/m2 over 3 hr daily for 4 days, either as a fixed dose per BSA, or to target an average daily AUC of 5,000 μMol-min ± 12% determined by a test dose of i.v. Bu at 32 mg/m2 given 48 hours prior to the high dose regimen. After the four daily Bu doses, there is a rest day, followed by two daily doses of Mel at 70mg/m2. Stem cells are infused the following day. Dilantin is administered for seizure prophylaxis. GVHD prophylaxis consists of tacrolimus and mini-dose methotrexate for pts receiving allo-SCT. Results: 14 pts (10 M/4 F) with median age 32 years (range 20–65) have been enrolled to date: MM (n=3), NHL (n=3), HD (n=8). The median number of prior chemotherapy regimens was 3 (range 2–8). At time of study entry, 2 pts were in CR2, 5 were in first relapse, and 7 had primary- or relapsed refractory disease. The median CD34+ cell dose infused was 4.88 x 106/kg (range 2.3–7.7). Median time to ANC ≥ 0.5 x 109/L was 9 days for auto-SCT pts (n=11), and 14 days for allo-SCT pts (n=3). Median time to platelet count ≥ 20 x 109/L was 9 days for auto-SCT pts, and 14.5 days for allo-SCT pts. All allo-SCT pts had 100% donor chimerism by day 30. 11 pts had i.v. Bu delivered per test dose guidance; 3 pts received fixed dose Bu at 130 mg/m2. The median daily systemic Bu exposure was 5292 μMol-min (range 4113–6734) in the dose-adjusted population. Median Bu clearance was slightly lower than reported in other studies at 99 ml/min/m2 (range 69–116). 7 of 11 pts were within ± 12% of the exposure target; 3 pts had AUCs above 6,000 μMol-min per dose. 3 of 11 evaluable pts have achieved complete remissions and 5 a partial response. With follow-up time of 7 to 117 days, there has been 1 death from disease progression (day 117). Grade II-IV acute GVHD was noted in 2 of 3 allo-SCT pts. The treatment was well tolerated, with grade I or II mucositis as the most common regimen-related toxicity. 2 auto-SCT pts developed grade III toxicity (mucositis and gastritis), and 1 allo-SCT pt developed grade III reversible acute renal failure. Grade II reversible hyperbilirubinemia was noted in 1 allo-SCT pt. No grade IV toxicity has been observed. Conclusion: Intravenous Bu-Mel is well tolerated with prompt neutrophil and platelet engraftment. Individualized PK-directed dosing of i.v. Bu is feasible, and likely contributes to the low toxicity profile of this regimen. It is too early to assess efficacy.

Weekly Bortezomib with or without Glucocorticosteroids Is Effective in Patients with Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2562-2562 ◽  
Author(s):  
Attaya Suvannasankha ◽  
Gina G. Smith ◽  
Rafat Abonour
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Side Effects ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Complete Response ◽  
Median Number ◽  
Time To Progression ◽  
Grade Iii

Abstract Well-tolerated, effective and simple regimens are warranted in multiple myeloma (MM). Bortezomib is an active novel agent for MM therapy. A phase III randomized trial in patients with relapsed and refractory MM demonstrates bortezomib to be superior to dexamethasone in time to progression and overall survival. The FDA approved schedule of bortezomib (days 1, 4, 8 and 11 infusion of a 21-day cycle) is rather inconvenient. We investigated the synergy between weekly bortezomib and glucocorticosteroids in order to the frequency of patients’ clinic visits. Methods: Patients with relapsed or refractory MM referred to Indiana University Cancer Center were offered bortezomib 1.3 mg/m2 by intravenous push and methylprednisone 500–2000 mg by intravenous infusion over 30 minutes. Treatments were given on days 1, 8 and 15 of 28-day cycles. Therapy was maintained as long as subjects’ diseases were responding and side effects were minimal. Both efficacy and tolerability of the regimen were evaluated. Results: Thirty patients were treated on the protocol. Twenty six received bortezomib in combination with methylprednisone, while 4 received single agent bortezomib. Patient age ranged from 50–79 years (median 62); there were 15 females and 15 males. Twenty-one patients (70%) had prior high dose chemotherapy and stem cell transplantation, including 2 with prior allogeneic stem cell transplantation. Thirteen patients were in third relapse or higher. The response was evaluable in 28 patients. Eighteen patients achieved clinical response (60 %), including 1 (3%) complete response, 1 (3%) near complete response, and 16 (53%) partial response. Five (17%) had stable disease, and 5 (17%) had progression. The median number of treatment cycles was 5 (range 2 to 12). Among responders, the median number of cycles given to achieve the best response was 3 cycles (range 1–8 cycles). Major adverse effects included neuropathy (2 grade III), gastrointestinal side effects (1 grade III) and congestive heart failure (1 grade III). The updated time to progression and overall survival will be presented at the meeting. Conclusion: Weekly bortezomib with or without steroid is a convenient and efficacious therapy for patients with heavily pretreated relapsed and refractory MM and should be further explored in a larger patient cohort.

Lack of prognostic relevance of alterations in the epidermal growth factor receptor—transforming growth factor-α pathway in human astrocytic gliomas

1996 ◽  
Vol 85 (4) ◽  
pp. 634-641 ◽  
Author(s):  
Andreas Waha ◽  
Axel Baumann ◽  
Helmut K. Wolf ◽  
Rolf Fimmers ◽  
Jürgen Neumann ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gene Amplification ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Who Grade ◽  
Transforming Growth Factor Α ◽  
Grade Ii ◽  
Astrocytic Gliomas ◽  
Who Grade Iii ◽  
Grade Iii

✓ Alterations in the epidermal growth factor receptor (EGFR) and its main ligand, transforming growth factor-α (TGFα), were investigated for a possible prognostic relevance in 125 astrocytic gliomas (44 World Health Organization (WHO) Grade II, 19 WHO Grade III, and 62 WHO Grade IV tumors). The TGFα and EGFR proteins were detected immunohistochemically using monoclonal antibodies. A positive immunoreaction to TGFa was detected in 33 (75%) of 44 WHO Grade II astrocytomas, 18 (95%) of 19 WHO Grade III astrocytoma, and 50 (81%) of 62 WHO Grade IV glioblastomas. No correlation between TGFα immunoreaction and duration of survival could be found. A positive EGFR immunoreaction was detected in seven (16%) of 44 WHO Grade II astrocytomas, five (26%) of 19 WHO Grade III astrocytomas, and 32 (52%) of 62 WHO Grade IV glioblastomas. Of these gliomas, 97 (26 WHO Grade II, 17 WHO Grade III, and 54 WHO Grade IV gliomas) were examined for EGFR gene amplification using a differential polymerase chain reaction assay. Amplification of the EGFR gene was detected in none of the WHO Grade II astrocytomas, one (6%) of 17 WHO Grade III astrocytomas, and 18 (33%) of 54 WHO Grade IV glioblastomas. Twenty-two of the tumors investigated showed a positive EGFR immunoreaction without detectable gene amplification (five WHO Grade II, four WHO Grade III, and 13 WHO Grade IV tumors). Gene amplification was invariably associated with a positive EGFR immunoreaction. For the entire study group, a strong correlation between EGFR alterations (gene amplification and positive immunoreaction) and survival could be found. However, this correlation only reflected the higher percentages of cases with EGFR alterations in malignant gliomas and was not an independent prognostic factor as determined by multifactorial analysis. These data demonstrate that EGFR alterations are frequent events in astrocytic gliomas and are largely restricted to glioblastomas. However, within one tumor grade they do not provide prognostic information.

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