Gemcitabine, Vinorelbine and Dexamethasone (GVDexa) As Second-Line Salvage Regimen in Relapsed and Refractory Hodgkin's Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3948-3948
Author(s):  
Anjana Joel ◽  
Prasanth Ganesan ◽  
Tenali Gnana Sagar ◽  
Krishnarathnam Kannan ◽  
Trivadi Ganesan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Second Line ◽  
First Line ◽  
Line Therapy ◽  
Baseline Characteristics ◽  
Third Line ◽  
Grade 3 ◽  
Stem Cell Collection

Abstract INTRODUCTION: Traditional platinum-based salvage regimens like DHAP, ICE are effective in relapsed Hodgkin's lymphoma (HL), but are more toxic. Gemcitabine based regimens are equally effective in salvage of lymphomas, but are less toxic and allow better stem cell collection for subsequent high dose therapy (HDT). There is limited data on the usefulness of gemcitabine based salvage regimens after the failure of salvage therapies like DHAP and ICE. At our center, we used a combination of gemcitabine, vinorelbine and dexamethasone (GVDexa), a non-platinum containing regimen in those patients who failed DHAP/ ICE based salvage treatment. METHODS: The records of patients with relapsed and refractory Hodgkin's lymphoma, who were treated with GVDexa, were reviewed. The regimen consisted of Gemcitabine 1000mg/m2 IV (D1,8), Vinorelbine 25mg/m2 IV (D1,8) Dexamethasone 40mg oral (D1-4) given as outpatient. It was given for 2-3 cycles until best response or till the patient underwent HDT. RESULTS: Between July 2010 to Jun 2015, 25 patients received GVDexa. The median age was 23 years (Range: 11 to 45 yrs) and 64% were males. Baseline characteristics are summarised in Table 1. Twenty-one patients (84%) had previous exposure to salvage therapy with DHAP/ ICE and GVDexa was given as third line treatment. The overall response rate was 48% (12/25) with complete response in 20% (5/25) and partial response in 28% (7/25). Toxicity: A total of 61 cycles [Median: 2 (Range: 1-6)] were delivered among 25 patients. Grade 3/4 haematological toxicities (neutropenia and thrombocytopenia) occurred in 9/61 (14.7%) cycles and febrile neutropenia occurred in 2 (3.2%) cycles. Grade 3/4 non-haematological toxicities were rare (paralytic ileus in 1 patient). There were no toxic deaths. Stem cell collection: Stem cell harvesting for HDT was attempted in 12 patients and was successful (> 2 million CD34 positive cells/kg) in 8 (67%) patients. Seven of these patients successfully completed HDT. Two patients who failed stem cell collection underwent reduced intensity conditioning allogeneic transplant. CONCLUSIONS: GVDexa, when used as third line therapy in relapsed and refractory HL shows promising response rates, with minimal toxicity. The high response rates achieved despite failure of first line platinum based salvage, points to the potential usefulness of this regimen as first line salvage therapy in refractory HL. GVDexa could emerge as a safe and effective non-platinum containing alternative regimen for second-line therapy in HL. Table 1. Baseline characteristics (N=25) PARAMETER Number (Range/Percentage) Age (median, range) 23 yrs (10 to 45 yrs) Male sex 16 (64%) Prior exposure to DHAP/ICE chemotherapy 21 (84%) Previous lines of chemotherapy (median, range) 2 (1 to 4) Time from 1st diagnosis to relapse (median, range) 31.5 months (4.3 to 153.7 months) Primary progressivea/refractory 13 (52) Stage III/IV at relapse 20 (80) Haemoglobin < 10g/dL at relapse 12 (48) a. Progressed within 3 months of completion of first line chemotherapy Disclosures No relevant conflicts of interest to declare.

High-Dose Carfilzomib and Dexamethasone As First-Line Treatment in Symptomatic Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4258-4258 ◽  
Author(s):  
Tomer M Mark ◽  
Sujitha Yadlapati ◽  
Lyubov Neglyad ◽  
Jennifer Bourke ◽  
David Jayabalan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Research Funding ◽  
Maximum Response ◽  
First Line ◽  
Disease Response ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3 ◽  
Stem Cell Collection

Abstract Background: Carfilzomib (Cfz) is approved for use in relapsed and refractory multiple myeloma (RRMM) at a dose of 27mg/m2 after escalation from 20mg/m2. The response rate for Cfz and dexamethasone (dex) as first-line therapy in multiple myeloma (MM) is unknown. Higher doses of Cfz have been shown to enhance overall response in RRMM (Lendvai 2014); the presence of a dose-response relationship of Cfz for first-line therapy in untreated MM has not been evaluated. A protocol of Cfz-Dex induction at two dosing levels, followed by BiRd (Clarithromycin 500mg PO BID, Lenalidomide (Len) 25mg for 21/28 days, Dex 40mg weekly) consolidation, and thereafter Len (10mg 12/28 days) maintenance, evaluated response and safety by Cfz dose level in patients (pts) with newly diagnosed symptomatic MM. The ORR and safety data for Cfz-Dex induction stratified by Cfz dose is reported. Methods: 70 patients with untreated MM were enrolled in a phase 2 study of Cfz-dex. Cfz-dex is: Cfz IV on D1, 2, 8, 9, 15, 16 of a 28-day cycle at a dose of 20mg/m2 on days 1, 2 of cycle 1 and 45mg/m2 thereafter and Dex 40mg on D1, 8, 15, 22. After the first 26 pts were enrolled, the protocol was amended to increase the Cfz from 45 to 56mg/m2. Screening echocardiogram and pulmonary function testing were performed. Brain natriuretic peptide (BNP) was measured with each cycle. Cfz-dex was continued until plateau in disease response (unchanged M-protein for 2 cycles). Elective stem cell collection was then performed in transplant eligible pts. This was followed by BiRd until 2nd response plateau, and then by LEN maintenance. Disease response evaluation was performed monthly with serum and urine protein electrophoresis, immunofixation, and free light chain analysis; bone marrow biopsy with skeletal imaging was used to confirm MM progression or complete response (CR). Cytogenetic testing was performed on CD138-selected cells. Results: 25 pts received Cfz-Dex at 45 mg/m2 and 44 (out of 45 enrolled) pts at 56 mg/m2 for at least 1 cycle and were evaluable for response. 56% of pts were ISS II/III and 64% had high-risk cytogenetics as per IMWG definition. Pts received a median of 5 cycles of Cfz-dex in both the 45 mg/m2 (range 1-10) and 56 mg/m2 groups (range 1-14). Maximum response to Cfz-dex is shown in Table 1. There was no difference in response between the 45 and 56mg/m2 groups (P = 0.20). Median time to PR and maximum response for the 45 and 56 mg/m2 cohorts were both 2 and 3 cycles, respectively. 42 pts had stem cell harvest. All collected stem cells to support at least two transplants (> 5 x 10^6 CD34/kg) in one mobilization attempt using G-CSF, with mean yield of 13.74x10^6 CD34/kg (range 5.94-32.14). 79% collected in 1 apheresis session. Adverse events (AEs) were notable for renal failure in 3 pts (2 Grade 2, 1 grade 3) and congestive heart failure in 1 pt (grade 3). Two of the 3 cases of renal failure occurred in the 56 mg/m2 cohort, all other AEs occurred in the 45mg/m2 cohort. All AEs resolved after stopping Cfz. There was no correlation with TTE, PFTs or serial BNPs and development of cardiac or pulmonary toxicity. Discussion: This is the first prospective study evaluating induction responses to Cfz-dex in MM. Cfz-dex is safe and active in induction at both 45 and 56 mg/m2, with an ORR of 93% and rate of >= VGPR of 68% despite a primarily high risk population. Specific dose did not correlate with response. Higher dose of Cfz did not lead to more toxicity. Cfz-dex induction led to successful stem cell collection in all attempts. Cfz-dex is a highly active and well-tolerated induction regimen. Transitioning to IMiD-based therapy after maximum response led to deeper responses with a remarkable 97% rate of VGPR or better. Table 1. Maximum Response with Cfz-Dex, followed by BiRD consolidation and lenalidomide maintenance: Response Category Cfz-Dex 45 mg/m2 Cfz-Dex 56 mg/m2 Overall Cfz-Dex phase BiRD phase Lenalidomide maintenance phase N = 25 (%) N = 44 (%) N = 69 (%) N = 44 (%) N = 33 (%) >= PR 22 (88) 42 (95) 65 (93) 44 (100) 33 (100) >= VGPR 16 (72) 31 (70) 45 (68) 42 (95) 32 (97) >= CR 3 (12) 2 (5) 5 (7) 12 (27) 15 (45) SCR 3 (12) 2 (5) 5 (7) 9 (20) 13 (39) CR 0 (0) 0 (0) 0 (0) 3 (7) 2 (6) VGPR 13 (52) 29 (66) 42 (61) 30 (68) 17 (52) PR 6 (24) 11 (25) 17 (25) 2 (5) 1 (3) SD 3 (12) 2 (5) 5 (7) 0 0 Disclosures Mark: Calgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Off Label Use: Carfilzomib as first line therapy in myeloma.. Rossi:Amgen: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Speakers Bureau. Pearse:Celegen: Consultancy. Perry:Takeda: Speakers Bureau; Celgene: Speakers Bureau. Pekle:Celgene: Speakers Bureau; Takeda: Speakers Bureau. Huang:Celgene: Research Funding. Coleman:Celgene: Speakers Bureau; Takeda: Speakers Bureau. Chen-Kiang:Celgene: Consultancy. Niesvizky:Celgene: Consultancy, Speakers Bureau.

T-Bird (thalidomide, clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], Dexamethasone) Therapy in Newly Diagnosed Symptomatic Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2937-2937
Author(s):  
Tomer M Mark ◽  
Manan Shah ◽  
Melissa Rodriguez ◽  
Ryann Quinn ◽  
Roger N Pearse ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Board Of Directors ◽  
First Line ◽  
Advisory Committees ◽  
Free Survival ◽  
Line Therapy ◽  
Grade 3 ◽  
Stem Cell Collection

Abstract Abstract 2937 Background: The addition of thalidomide to BiRD therapy (clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], dexamethasone) may enhance anti-myeloma activity of the combination while not adding to overall regimen toxicity, given the different side effect profiles of thalidomide and lenalidomide. We now report an update of the phase 2 trial of T-BiRD (thalidomide/Thalomid®, clarithromycin/[Biaxin®], lenalidomide/[Revlimid®], dexamethasone) in up-front treatment of symptomatic multiple myeloma (MM). Methods: Twenty-six patients with newly diagnosed symptomatic MM received T-BiRD. T-BiRD is clarithromycin 500mg twice daily; dexamethasone 40mg on days 1, 8, 15, 22; and lenalidomide 25mg for days 1–21 of a 28-day cycle. Thalidomide was given at a dose of 50mg daily for the first week and thereafter at 100mg daily. All subjects had thromboprophylaxis with aspirin. Disease response evaluation was performed monthly with immunoelectrophoresis and free light chain analysis; bone marrow biopsy with skeletal imaging was used to confirm MM progression or complete response (CR). Treatment was continued as tolerated by the patients until disease progression. Results: Twenty-six patients were enrolled. The median number of T-BiRD cycles delivered was 6.5 (range 0–17). The overall response rate (ORR) to T-BiRD (audited at time of autologous stem cell transplant [ASCT] or other planned change in therapy) was 77% (4% progressive disease (PD), 19% stable disease (SD), 42% partial response (PR), 31% very good partial response (VGPR), 4% CR). Eight patients (31%) withdrew from study, including 4 (15%) early withdrawals prior to completion of cycle 2 (1 due to Grade 4 rash, 2 due to Grade 3 rash, and 1 due to renal failure secondary to MM). Excluding these early withdrawals, ORR was 86% (5% PD, 10% SD, 45% PR, 36% VGPR, 5% CR). In these patients, median time to PR was 1 cycle [range 1–5]; the median time to max response was 4 cycles [range 1–7]. All eighteen patients who electively underwent autologous stem cell collection were successful, with median 16.317 CD34+ cells/kg collected [range 5.8–43.9] over a median of 1.5 apheresis sessions [range 1–5]. Eleven subjects underwent ASCT as part of a first line of therapy with T-BiRD induction; ORR to first line therapy in these subjects was 100%, with 18% PR, 46% VGPR, and 36% CR. At 4 years of study follow-up for 1st line therapy, median progression free survival (PFS) and event free survival (EFS) was 135.6 and 65.3 weeks respectively. Median overall survival (OS) was not reached; at 4-year follow-up, 4 patients had died of progressive myeloma, giving an overall survival rate of 84.5%. Twelve patients experienced grade 3 non-hematologic toxicity (weakness: 4; rash: 3; popliteal vein thrombosis: 2; respiratory infection: 1; hyperglycemia: 1; anorexia/dysgeusia: 1; renal insufficiency: 1; dizziness: 1; psychomotor agitation: 1; myocardial infarction: 1). One subject had grade 4 rash during cycle 1. 1 subject died of progressive myeloma prior to completion of 10 days of cycle 1. Conclusions: T-BiRD is a highly active regimen in treatment-naïve multiple myeloma, with prolonged responses achieved; however, early treatment toxicity precluded extended use in up to a third of patients. Responding patients achieved PR within 1 cycle, indicating that this regimen may be useful when a swift drop in paraprotein is desired. T-BiRD allows for successful autologous stem cell collection and transplant outcomes. These data support the use of immunomodulatory-based regimens in the upfront treatment of MM and highlight the potential additive toxicities of the simultaneous administration of thalidomide and lenalidomide. Disclosures: Mark: Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Off Label Use: The combination of thalidomide and lenalidomide was tested in relapsed myeloma; the combination is not FDA-approved. Zafar:Celgene Corp: Speakers Bureau. Pekle:Celgene Corp: Speakers Bureau. Coleman:Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Niesvizky:Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

First-line treatment with Bendamustine plus Rituximab for patients with indolent non-Hodgkin’s lymphoma or Mantle cell lymphoma: Real-world experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19540-e19540
Author(s):  
Rouslan Kotchetkov ◽  
David Susman ◽  
Lauren Gerard ◽  
Erica DiMaria ◽  
Derek Wayne Nay
Keyword(s):  
Adverse Events ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
First Line ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Mantle Cell ◽  
Grade 3

e19540 Background: Bendamustine plus rituximab (B+R) was established as a preferred first line therapy for patients with previously untreated indolent non-Hodgkin’s lymphoma based on the BRIGHT and STIL trials. However, only few reports on efficacy and safety data of this combination in the real-world setting are available to-date. Methods: We conducted a retrospective review of patients who received therapy with standard doses of B+R in our cancer center from June 2013 to January 2021. Patients with indolent non-Hodgkin’s lymphoma (iNHL) and mantle cell lymphoma (MCL) who received more than one cycle of B+R were evaluated. Results: Amongst a total of 201 patients 56% were males and 44% females. Median age at B+R initiation was 72 years (range 34-94). Follicular lymphoma (FL) (50.3%), marginal zone lymphoma (MZL) (19.4%), and lymphoplasmacytic lymphoma (LPL) (14.5%) were the most common iNHL. Stage 3 and 4 diseases represented 19.9% and 68.6% of patients. Extranodal disease was found in 35.8%. The proportion of patients with high risk disease was 48.5% for FL (FLIPI ≥3), 86.6% for LPL (WMISS score ≥2), and 80.5% for MCL (MIPI score ≥6.2). Prior history of secondary malignancy had 23.4% of patients; 11.4% patients had ECOG 3. Most common indications for B+R initiation were bulky symptomatic lymphadenopathy (69.1%), cytopenia (36.8%) and constitutional symptoms (36.8%). Fifty-eight percent of patients had more than one indication for therapy. Median number of B+R cycles delivered was 6 (range: 1-6), median dose of bendamustine was 90 mg/m2 (range 45-90). Full doses of treatment were given in 66.7% of patients, reduced in 33.3% with mean dose 78.3 mg/m2. A total of 50.8% completed 6 cycles with no delays, in 49.2% treatment was delayed (mean delay time 1.8 weeks). Overall response was 94.5%, with 77.6% complete and 16.9% partial remission. Median duration of follow-up was 35 months (range: 4-91). At the end of follow-up, event free survival (EFS) was 77.1% and overall survival (OS) was 79.6%. Six percent of patients relapsed, 8% developed secondary hematological malignancies, including 14 cases of aggressive B-cell lymphoma and 2 cases of MDS. 16.9% of patients required support with G-CSF. Grade 3-4 neutropenia was recorded in 22.4%, febrile neutropenia in 7.5%, grade 3-4 anemia in 7.9%, and grade 3-4 thrombocytopenia in 3.9% of patients. Rituximab-associated infusion reactions, skin rash, thrombophlebitis, and infection were the most common non-hematological adverse events. A total of 80.6% of patients proceeded to rituximab maintenance. Conclusions: B+R chemoimmunotherapy is feasible to administer in non-clinical trial setting. Despite more dose reduction as compared to STIL trial, B+R retained its efficacy with comparable EFS and OS. No new adverse events or increase in secondary malignancies were found.

scholarly journals CEPP(B): an effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin's lymphoma

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1293-1298 ◽  
Author(s):  
NJ Chao ◽  
SA Rosenberg ◽  
SJ Horning
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Medical Center ◽  
Palliative Therapy ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Eighty-three patients with intermediate- or high-grade non-Hodgkin's lymphoma were treated with CEPP(B) (cyclophosphamide, etoposide [VP- 16], procarbazine, and prednisone with or without bleomycin) chemotherapy at Stanford University Medical Center (Stanford, CA) from January 1982 through June 1989. Sixty-nine received CEPP(B) as second- line or subsequent therapy after relapse from previous combination chemotherapy, and 14 patients received CEPP(B) as first-line therapy. Of 75 patients evaluable for response, 30 patients (40%) achieved a complete response (CR) and 24 patients (32%) achieved a partial response (PR), providing an overall response rate of 72%. Complete responses were recorded on 21 of 61 (34%) patients with recurrent disease and 9 of the 14 patients who received CEPP(B) as first line therapy (64%). Myelosuppression was the major side effect of treatment, resulting in eight neutropenic-febrile episodes from a total of 253 courses. A single fatal toxic event occurred on a patient who developed adult respiratory distress syndrome. Overall, CEPP(B) was well- tolerated and proved to be effective palliative therapy for patients with non-Hodgkin's lymphoma after relapse. As such, CEPP(B) may be considered for cytoreduction before ablative therapy and bone marrow transplantation. CEPP(B) may also be considered for initial therapy in selected patients who cannot tolerate doxorubicin-containing regimens.

Phase I/II Dose-Escalation Study of Tositumomab and Iodine I 131 Tositumomab for Relapsed/Refractory Classical or Lymphocyte-Predominant Hodgkin’s Lymphoma: Feasibility and Initial Safety

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3059-3059 ◽  
Author(s):  
Heather A. Jacene ◽  
Yvette L. Kasamon ◽  
Richard F. Ambinder ◽  
Wayne Kasecamp ◽  
Donna Serena ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Phase I ◽  
Dose Escalation ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Cd20 Expression ◽  
Grade 3 ◽  
Experienced Grade ◽  
131I Tositumomab

Abstract Objective : CD20 has been recently recognized as a potential immunotherapeutic target in Hodgkin’s lymphoma (HL), being expressed in all malignant cells in lymphocyte-predominant HL (LPHL), a subset of classical HL (cHL), and in normal surrounding B-cells. Recent data also suggest that the cancer stem cell in cHL is phenotypically distinct from Reed-Sternberg cells and expresses B-cell antigens including CD20 (Jones RJ et al, Blood2006; 108: abstract 470). Given the single agent activity of the unlabeled antiCD20 monoclonal antibody, rituximab, in HL, we are conducting a phase I/II study of tositumomab and Iodine I 131 (131I-) tositumomab (BEXXAR ®, GlaxoSmithKline) for HL in the relapsed/refractory setting, regardless of tumor CD20 expression. We report on feasibility and initial safety. Methods : Separate dose-escalation studies were performed for patients with and without prior stem cell transplantation, starting at 55 and 75 cGy total body radiation doses (TBD), respectively. Dosimetry imaging studies were performed after administration of 450 mg tositumomab and 5 mCi 131I-tositumomab. Patients then received a single patient-specific therapeutic dosage of 450 mg tositumomab and 131I-tositumomab. The TBD was escalated or de-escalated based on a continual reassessment method (CRM). Results : Seven patients with relapsed/refractory disease (6 cHL, 1 LPHL; mean age 36 ± 9) have been enrolled. Four patients with cHL were negative for CD20 on malignant Reed-Sternberg cells and two had mixed expression. Three patients who had failed transplant received a 55 cGy TBD of 131I-tositumomab and three ineligible for transplant received 75 cGy. No dose-limiting toxicities were observed and based on the CRM, the TBD was escalated to 79 cGy for the post-transplant group and to 87 cGy for the no transplant group. To date, one in the next post-transplant cohort received 79 cGy and experienced grade 1 thrombocytopenia and grade 3 lymphopenia with count recovery. No adverse reactions occurred during infusion of unlabeled or radiolabeled tositumomab, and the agent was generally well-tolerated in all dosing cohorts. The expected hematologic adverse events were common and are summarized in the Table. No patients experienced grade 3 or 4 non-hematologic toxicity. One patient had grade 1 or 2 fever, chills, joint and muscle pain suggesting possible human anti-mouse antibody formation and immune complex mediated inflammation. One patient with LPHL had a complete response, two with cHL had stable disease (1 mixed CD20 expression, 1 CD20 negative) and 4 with cHL had progressive disease (1 mixed CD20 expression, 3 CD20 negative) at 12 weeks post-131I-tositumomab. Conclusions : Tositumomab and 131I-tositumomab can be safely administered to patients with relapsed/refractory HL. Major toxicities are hematologic, similar to its effect in patients with non-Hodgkin’s lymphoma. The CRM was used successfully for determining TBD for subsequent cohorts, and the transplant recipients have tolerated higher doses than those previously reported in non-Hodgkin’s lymphoma. These encouraging preliminary data support further dose escalation and suggests some therapeutic effect of tositumomab and 131I-tositumomab against HL. Hematologic Adverse Events All (n=7) Grade Range of Duration of Grade 3/4 Toxicity (days) 1/2 3 4 Thrombocytopenia 6 0 1 1 7–34 Neutropenia 2 1 0 1 7 Lymphopenia 7 2 3 2 1–35 Anemia 2 1 1 0 4

Is second-line targeted therapy beneficial in patients (pts) with differentiated thyroid cancer (DTC) after first-line sorafenib (SOR) failure?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e17016-e17016
Author(s):  
Ramona Dadu ◽  
Catherine E Devine ◽  
Mike Hernandez ◽  
Naifa Busaidy ◽  
Steven Waguespack ◽  
...  
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Differentiated Thyroid Cancer ◽  
Second Line ◽  
Phase Ii Trials ◽  
First Line ◽  
Promising Strategy ◽  
Line Therapy ◽  
Investigational Drugs ◽  
Baseline Characteristics

e17016 Background: SOR has demonstrated efficacy in phase II trials but responses are not durable. 2nd line therapy is used in clinical practice however there are no data showing clinical benefit with this approach. We sought to determine if 2nd line targeted therapy was beneficial after SOR failure. Methods: Adult pts with DTC treated with 1st line SOR for >3 months were included. We compared overall survival (OS) in pts who received only 1st line SOR (grp 1) with pts treated with 2nd line therapy after 1st line SOR failure (grp 2). OS was defined as time after SOR failure until death. SOR failure was defined as discontinuation due to progression or intolerable toxicity. Results: We identified 62 DTC pts from 2006-2012 who were treated with 1st line SOR. 10 pts in grp 1 were excluded due to missing data, secondary unrelated cancers and <3 mo on SOR. We included 52 pts: 31 in grp 1 and 21 in grp 2. Baseline characteristics were similar between groups (Table). FTC was more frequent in grp 2. 2nd therapy included sunitinib, pazopanib, vemurafenib, and other investigational drugs. Median time on treatment with 2nd line therapy was 14.5 mo. Median OS in grp 1 and grp 2 was 6 and 50 mo, respectively (p=0.002). After excluding pts for death <3 mo after SOR end, median OS was 20 and 50 mo; there was a trend toward significance (p=0.07). Response and updated analysis will be reported at the meeting. Conclusions: Our study shows that pts receiving 2nd line therapy after SOR failure had a long OS despite more pts with FTC in this group. Acknowledging the limitations of a retrospective study, we conclude that in DTC pts, salvage targeted therapy after SOR failure appears to be beneficial and a promising strategy. [Table: see text]

Association of UGT1A1 gene polymorphism with the safety and efficacy of irinotecan monotherapy for advanced gastric cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 16-16 ◽  
Author(s):  
Toshifumi Yamaguchi ◽  
Satoru Iwasa ◽  
Hirokazu Shoji ◽  
Yoshitaka Honma ◽  
Atsuo Takashima ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Initial Dose ◽  
Uridine Diphosphate ◽  
Second Line ◽  
Safety And Efficacy ◽  
Line Therapy ◽  
Third Line ◽  
Grade 3 ◽  
Ugt1a1 Genotype

16 Background: The uridine diphosphate glucuronosyltransferase (UGT) 1A1, which transforms SN-38 into SN-38 glucuronide, is a key enzyme involved in the metabolism of irinotecan. Previous studies showed that UGT1A1 genotype is related to the toxicity of irinotecan-based chemotherapy in metastatic colorectal cancer. The purpose of this study was to investigate the relationship between UGT1A1genotype and safety and efficacy of irinotecan monotherapy in patients with advanced gastric cancer. Methods: We reviewed the data of 208 patients who were tested for UGT1A1 genotype and treated with irinotecan-based chemotherapy for advanced gastric cancer from 2009 to 2014. We evaluated the efficacy and safety of irinotecan monotherapy in the three groups with wild-type (WT), single heterozygosity (SH), and homozygosity/double heterozygosity (Homo-DH) classified by the genotypes for UGT1A1*28 or UGT1A1*6. Results: A total of 117 patients received irinotecan monotherapy: 40 patients in second-line, 74 in third-line, and 3 in forth-line therapy. The UGT1A1genotype was WT in 62 patients (53.0%), SH in 41 (35.0%), and Homo-DH in 14 (12.0%). Patients’ characteristics were similar among the three groups. The initial dose of irinotecan was reduced in 10 patients (16%) with the WT genotype, in 11 (27%) with SH, and in 10 (71%) with Homo-DH. Grade 3-4 neutropenia, diarrhea, and febrile neutropenia occurred in 13/22/64%, 6/5/21%, and 2/7/50% of WT/SH/Homo-DH patients. Median time to treatment failure of second-line and third-line therapies were 2.4/2.8/3.3 months and 2.4/2.3/1.3 months in WT/SH/Homo-DH patients. Median overall survival of second-line and third-line therapy were 7.9/9.9/4.6 months and 6.9/6.3/2.8 months in WT/SH/Homo-DH patients. Conclusions: Patients with UGT1A1 Homo-DH displayed high frequency of grade 3-4 toxicities, although the initial dose of irinotecan was reduced in some patients. UGT1A1 polymorphism may be related to the efficacy of irinotecan monotherapy in second- and third-line treatments for advanced gastric cancer.

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