CTNI-33. METRONOMIC TEMOZOLOMIDE THERAPY IN HEAVILY PRETREATED PATIENTS WITH RECURRENT GLIOBLASTOMA: A LARGE MONO-INSTITUTIONAL RETROSPECTIVE STUDY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi66-vi67
Author(s):  
Alberto Bosio ◽  
Giulia Cerretti ◽  
Marta Padovan ◽  
Mario Caccese ◽  
Valentina Guarneri ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Recurrent Glioblastoma ◽  
First Line ◽  
First Line Therapy ◽  
Common Grade ◽  
Heavily Pretreated ◽  
Third Line ◽  
Grade 3 ◽  
Line Of Therapy ◽  
Ecog Ps

Abstract BACKGROUND Despite advances in surgical and first-line treatment, all glioblastoma pts relapse. The aim of this study is to evaluate the benefit of metronomic temozolomide (mTMZ) for recurrent glioblastoma. METHODS 120 pts treated at Veneto Institute of Oncology from September 2013 to March 2021 were retrospectively reviewed. Major inclusion criteria were: first-line therapy with Stupp protocol, relapse after first or subsequent line of therapy, treatment with mTMZ schedule (50mg/m2 continuously), hystologically confirmed diagnosis. RESULTS mFollow-up was 15.6ms, mAge 59ys (range 18-81), ECOG PS 0-2 in 107pts (89%) and 3 in 11 (9%). MGMT was methylated in 66 of 105 (62%) evaluable pts, IDH mutated in 9 of 106 (8%). mNumber of prior lines of treatment was 2 (range 1-7); 41% of pts received mTMZ beyond the third line. mTime between last standard TMZ (sTMZ) cycle and mTMZ administration was 6ms (range 1-50); 40% of pts started mTMZ after 3ms from sTMZ. All pts were evaluable for response: 3 (2%) and 48 (40%) showed PR and SD. mOS from the start of mTMZ was 5.4ms (95% CI 4.3-6.4), mPFS 2.6ms (95% CI 2.3-2.8). On univariate analysis, MGMTmet and MGMTunmet pts had a mOS of 5.6 and 4.4ms (p= 0.03); mOS for pts with ECOG PS > or ≤ 2 was 2.3 and 6.0ms (p< 0.001). On multivariate analysis, MGMTmet status (HR= 2.3, 95% CI, p= 0.004) and ECOG PS (HR= 0.5, 95% CI, p= 0.017) remained significant for PFS; ECOG PS (HR= 0.4, 95% CI, p= 0.001) was the only factor significantly associated with OS. The most common grade 3-4 hematologic toxicities were lymphopenia (10%) and thrombocytopenia (3%). Grade 3-4 nonhematologic toxicities were uncommon. CONCLUSIONS Rechallenge with mTMZ can be a well tolerated treatment option for recurrent glioblastoma, even in heavily pretreated pts. Pts with MGMTmet and good ECOG PS might report the major benefit.

Randomized trial of sequence vs. combination of capecitabine (X) and docetaxel (T): XT vs. T followed by X after progression as first-line therapy for patients (pts) with metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 571-571 ◽  
Author(s):  
S. Beslija ◽  
N. Obralic ◽  
H. Basic ◽  
A. Tatarevic ◽  
M. Naila ◽  
...  
Keyword(s):  
Metastatic Breast ◽  
Treatment Rate ◽  
First Line ◽  
First Line Therapy ◽  
Highly Active ◽  
Common Grade ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Weekly Cycles

571 Background: Capecitabine (Xeloda [X]) and docetaxel (Taxotere [T]) are highly active single agents in MBC. The XT combination leads to superior overall survival (OS), time to progression (TTP) and response rate (RR) vs. T alone in anthracycline-preatreated MBC [O’Shaughnessy et al. J Clin Oncol 2002], although only one third of pts in the T group received X after progression. We designed this study to determine whether XT is better than sequential T→X in first-line MBC. Methods: 100 pts with measurable MBC, prior adjuvant anthracyclines (100%) but no prior chemotherapy for MBC and KPS ≥70 received 3-weekly cycles of either XT (X 1250mg/m2 bid d1–14 + T 75mg/m2 d1) or T→X (T 100mg/m2 d1 followed after progression by X 1250mg/m2 bid d1–14). X monotherapy data were not considered in the RR or TTP analyses but were included for OS and safety. Results: The XT and T→X arms were well balanced for prognostic factors: median age 48 (29–59) vs. 51 (31–64) years; median KPS 100 (70–100) in both arms; hormone-responsive disease 20 vs. 16%; dominant metastatic sites (liver 42 vs. 44%, lymph nodes 34 vs. 36%, lung 28 vs 24%, bone 20 vs 18%); number of involved organs (1 = 58 vs. 52%, >1 = 42 vs. 48%); median interval since prior adjuvant anthracyclines (18.5 vs. 17.0 months). Efficacy findings are shown in the table . 74% of the pts in the T→X arm crossed-over to X on progression. The post-study treatment rate was similar in both arms. The most common grade 3/4 adverse events (>5% of pts) with XT vs. T→X were: hand-foot syndrome 18 vs. 4%; stomatitis 16 vs. 8%; neutropenia 12 vs. 14%; neutropenic fever 12 vs. 14%; diarrhea 12 vs. 8%; fatigue 8 vs. 12%; alopecia 6 vs. 8%; edema 4 vs. 8%. Dose reductions were necessary for 52% of pts on XT and 36% of pts on T→X. Conclusions: XT provides significant RR, TTP and OS advantages over T→X. XT should be the standard therapy in fit poor-prognosis pts with aggressive disease. [Table: see text] No significant financial relationships to disclose.

Results of a phase II trial of cetuximab + XELIRI as first-line therapy of patients with advanced and/or metastatic colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4094-4094
Author(s):  
T. H. Cartwright ◽  
P. Kuefler ◽  
A. Cohn ◽  
W. Hyman ◽  
M. Yoffe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Allergic Reaction ◽  
Metastatic Colorectal Cancer ◽  
First Line ◽  
Prior Therapy ◽  
First Line Therapy ◽  
Duration Of Response ◽  
Grade 3 ◽  
Ecog Ps ◽  
Dose Reductions

4094 Background: We have previously shown that capecitabine/irinotecan (XELIRI) is effective and well-tolerated in metastatic colorectal cancer (mCRC). Cetuximab, a monoclonal IgG1 antibody that binds to the extracellular domain of EGFR, is active in mCRC alone or in combination with chemotherapy. This study was designed to evaluate if cetuximab (Erbitux®) added to XELIRI improves outcome in first-line treatment of mCRC. Methods: Subjects had histologically confirmed colorectal adenocarcinoma with T4 lesions that were unresectable after preoperative chemoradiation therapy and/or metastases. The study regimen was capecitabine 1700 mg/m2 (850 mg/m2 PO BID Days 1–14), irinotecan 200 mg/m2 IV Day 1 every 3 weeks, and weekly cetuximab (initial dose 400 mg/m2 IV over 120 minutes, subsequent doses 250 mg/m2 over 30 minutes). Results: Between February and October 2005, 70 subjects enrolled. Baseline characteristics: 43 males (61%), median age 61.5 years, and ECOG PS 0/1= 66%/34%; 94% of subjects had adenocarcinoma. Prior therapy; surgery (91%), chemotherapy (20%), or radiotherapy (7%). Responses (pts >2 cycles) were; CR (4%), PR (36%), SD (40%) and PD (20%); 15 patients failed treatment; (n=4 allergic reaction, n=2 MD request, n=2 withdrew consent, n=2 Grade 4 neutropenia, and n=5 other AEs). The overall response rate was 40% and the disease control rate was 80%. Median duration of response was 8.8 months (range, 2.6–15.1) and median time to response was 2.0 months (range, 1.2–8.3). 64% of patients remain alive; of the 25 deaths, 84% were due to PD. No death was drug related. The most frequent Grade 3 and 4 treatment-related adverse events (AEs) included: diarrhea (25%), neutropenia (18%), nausea/vomiting (12%), rash and dehydration (9%, each), HFS and fatigue (7%), and allergic reaction (6%). 54% of patients required dose reductions. To date, 64 patients (91%) have gone off study, primarily due to PD (39%) or AE (33%); 3 patients remain on treatment. Conclusions: The combination of cetuximab and XELIRI is feasible and tolerable in first line mCRC. Toxicities are expected and manageable with dose reductions/delay. Funded in part by Bristol-Myers Squibb, Plainsboro, NJ. No significant financial relationships to disclose.

scholarly journals Patient Profile and Treatment Patterns in a Commercially Insured Population with Follicular Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5880-5880
Author(s):  
Nathan H Fowler ◽  
Yanni Hao ◽  
Stephen Lim ◽  
Guifang Chen ◽  
Frank Li ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Second Line ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line ◽  
Line Of Therapy

Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. Patient characteristics and burden of FL are incomplete and vary from previous studies. This study evaluated patient profile, including patient characteristics, treatment patterns, and duration using real-world data. Methods: Using the Truven MarketScan® databases, patients with FL who were newly initiated with FL indicated regimens were identified from 1/1/2010-12/31/2013 (initial treatment identification period). Patients were selected if they were ≥18 years old, had 1 FL ICD-9 code (202.0) as primary or secondary diagnosis, at least 1 FL commonly prescribed systemic anti-cancer therapy after the diagnosis, and did not use any FL indicated regimen in the past 6 months prior to first agent included in the initial treatment identification period. These patents were followed ≥3 months or to June 30, 2018. Primary outcomes were the distribution of regimens by line, the number of patients who switched from first- to second-line therapies, and from second- to third-line therapies. The treatment duration by line of therapy and regimen were also analyzed. Discontinuation was defined as 3 months without receiving a regimen after treatment. Results: This study identified 4,970 patients who initiated treatment for FL. Of these patients, 48.1% were female (n=2,390), with a mean age of 62.0 (SD: 14.0) years. The average follow-up time was approximately 2 years (median: 733 days). In this analysis, 4,970 patients with FL received first-line therapy for 153 days (median: 94 days), 1,985 received second-line therapy (39.9% of patients who received first-line therapy) for 208 days (median: 80 days), and 664 received third-line therapy (13.4% of patients who received first-line therapy) for 117 days (median: 43 days). Of the 4,970 patients on first-line therapy, 453 (9.1%) remained on first-line therapy, 2,532 (51.0%) discontinued treatment, and 1,985 (39.9%) patients switched to the next line of therapy during the follow-up period. Of the 1,985 patients who switched to second-line therapy, 328 (16.5%) remained by the end of follow-up period, 993 (50.0%) discontinued, and 664 (33.4%) switched to the next line of therapy during the follow-up period. Of the 664 patients who switched to third-line therapy, 125 (18.8%) remained, 269 (40.5%) discontinued, and 270 (40.7%) switched to the next line of therapy. The most common first-line regimens in descending order received by patients were rituximab (n=1,478, 29.7%), R-CHOP (n=1,368, 27.5%), BR (n=1,050, 21.1%), R-CVP (n=371, 7.5%), and FCR (n=63, 1.3%). Second-line treatment regimens were (N=1,985) rituximab (n=992, 50.0%), BR (n=202, 10.2%), R-CHOP (n=138, 7.0%), and R-CVP (n=120, 6.1%). Third-line treatment regimens were (N=664) rituximab (n=228, 34.3%), BR (n=91, 13.7%), R-CHOP (n=75, 11.3%), cyclophosphamide (n=35, 5.3%) and R-CVP (n=31, 4.7%). Conclusion: This data set describes the percentage of patients that transition from first- to second-line and second- to third-line treatment for FL. The primary regimens used across the treatment lines conform to those recommended by the NCCN guidelines. In addition, smaller numbers of non-recommended regimens were reported. Disclosures Fowler: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; ABBVIE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Lim:Novartis Pharmaceuticals Corporation: Employment. Chen:Novartis Pharmaceuticals Corporation: Consultancy, Employment. Li:Novartis Pharmaceuticals Corporation: Employment. Arcona:Novartis Pharmaceuticals Corporation: Employment.

Phase I study of the IXO regimen, irinotecan (I), capecitabine (X), oxaliplatin (O), as first-line therapy for metastatic colorectal cancer: Final survival results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4082-4082
Author(s):  
J. Maroun ◽  
D. Jonker ◽  
C. Cripps ◽  
R. Goel ◽  
T. Asmis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Line Treatment ◽  
First Line ◽  
Common Grade ◽  
Grade 3 ◽  
Ecog Ps ◽  
First Line Treatment

4082 Background: This study was designed to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and efficacy of the IXO regimen when used as first-line treatment for metastatic colorectal cancer (mCRC). Methods: Patients with ECOG PS 0–2, histologically proven, chemo-naïve, non-resectable mCRC were eligible. Phase I starting doses were as follows: I (180 mg/m2 i.v.) d1, X (850 mg/m2 bid orally) d2–15, O (85 mg/m2 i.v.) d1; q3w. Dose escalation (3+3 design) was based on toxicity observed at previous dose levels (DL) until DLT and the MTD were reached. Results: 39 pts (31 male/8 female, median age 58 years, ECOG PS 0–1 in 37, 95%) received a median of 11 cycles (range 1–34) at 8 DLs. 39 pts were evaluable for toxicity. The most common grade 3/4 hematological adverse events (AEs) were granulocytopenia (60%) and fever/febrile neutropenia (18%). The most common grade 3 non-hematological AEs were diarrhea (15%), vomiting (10%), fatigue (8%). No grade 3/4 neuropathy was reported. DLTs: 1 DLT was observed at each of the first 4 DLs, no DLTs at DL5 & 6, 1 at DL7 and 2 at DL8. MTD was reached at DL8. The recommended phase II dose (DL7) is as follows: I (160 mg/m2), X (950 mg/m2), O (100 mg/m2). Efficacy: 38 pts are evaluable for efficacy. The RR is 74% (95% CI 60–89), including 4 CRs, 25 PRs and 6 SDs. The disease control rate is 90% (95% CI 80–100). 10 (26%) pts had subsequent liver surgery with curative intent; 1 had lung resection. Median progression-free survival was 12.3 months (95% CI, 8–17). Overall median survival was 26.4 months (95% CI, 13–36). Conclusions: Diarrhea is the main DLT. Severe neutropenia was of short duration and manageable. The IXO regimen is well tolerated and highly effective as first-line treatment for mCRC. It appears to be particularly effective in downsizing of initially unresectable colorectal cancer liver metastases. A phase II study to confirm the efficacy/safety of IXO in combination with bevacizumab (Avastin) is ongoing. Supported by: Hoffmann La-Roche, Sanofi-Aventis, Pfizer Canada. [Table: see text]

Phase I study of everolimus (RAD001) with irinotecan (Iri) and cetuximab (C) in second-line metastatic colorectal cancer: Hoosier Oncology Group GI05-102.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 523-523 ◽  
Author(s):  
B. Myre ◽  
M. Yu ◽  
J. Picus ◽  
J. A. Bufill ◽  
W. A. Harb ◽  
...  
Keyword(s):  
Phase I ◽  
Infusion Reaction ◽  
Maximum Tolerated Dose ◽  
Stopping Rules ◽  
First Line Therapy ◽  
Randomized Phase Ii ◽  
Common Grade ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps

523 Background: Preclinically, mTOR and EGFR inhibitors are synergistic. We hypothesize that the mTOR inhibitor RAD001 would enhance efficacy and prevent resistance when added to an anti-EGFR agent. The purpose of the phase I portion of this study was to determine the safety and maximum tolerated dose (MTD) of daily RAD001 combined with weekly Iri and C in mCRC. Methods: Pts who failed first-line therapy, including an Iri-regimen, were treated with Iri 125 mg/m2 weekly x 2 every 3 weeks, C 400 mg/m2 loading dose, then 250 mg/m2 weekly, and escalating doses of RAD001 orally: 5 mg qod, 5 mg qd and 10 mg qd during 21-day cycles, with a “3+3” design. The study was amended after the first 9 pts enrolled, to include stopping rules for excessive toxicity beyond what was expected for diarrhea, nausea/vomiting and febrile neutropenia due to Iri, and skin rash due to C. Enrollment excluded pts with UGT1A1*28, but allowed KRAS mutated mCRC. RAD001 PK was done on C2D1, and archival tumors were analyzed for pharmacodynamic markers. Results: 28 pts were enrolled, median age 61 y (25-77), 15 male, ECOG PS 0/1 (19/9). Reasons for treatment discontinuation were: PD (7), adverse events (AEs) (6), pt withdrawal, symptomatic deterioration and non-compliance (1 each). Prior to study's amendment* (n=9), 3 pts were not evaluable for DLT due to: Iri intolerance after one dose (1), non-compliance (1) and gr 3 C infusion reaction (1). DLTs and number of cycles are listed in Table. Following protocol amendment, 2 pts had DLT in cohort 3 (gr 3 mucositis), thus the MTD was 5 mg RAD001. The most common grade 3/4 AEs were: diarrhea (10), neutropenia (5), fatigue (4), acne-rash (4), mucositis (2), nausea (2), vomiting (1). Among 19 pts evaluable for response, there were 1 CR, 2 PR, (RR 16%), 9 SD (47%), 7 PD (37%). PK and pharmacodynamic data is ongoing. Conclusions: The MTD of RAD001 of 5 mg QD with Iri/C weekly is safe and clinically active. A randomized phase II study is near starting accrual. [Table: see text] [Table: see text]

First-Line Treatment with Rituximab Combined with Intravenous or Oral Fludarabine for Patients with Extranodal Mucosa Associated Lymphoid Tissue (MALT) Lymphoma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2007-2007
Author(s):  
Antonio Salar ◽  
Eva Domingo-Domènech ◽  
Cristina Estany ◽  
Miguel Canales ◽  
Octavio Servitge ◽  
...  
Keyword(s):  
Malt Lymphoma ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
First Line ◽  
The Third ◽  
First Line Therapy ◽  
Improved Outcomes ◽  
Significant Addition ◽  
Grade 3

Abstract Backgroud: Synergistic antitumor effect with combination of fludarabine and rituximab has been demostrated on MALT cells. Addition of rituximab to other drugs has improved outcomes in several types of NHL without a significant addition of toxicity. Our aim was to evaluate the safety and efficacy of rituximab combined with fludarabine (RF) in first-line therapy for extranodal MALT lymphoma. Patients and methods: Adult patients with untreated extranodal MALT lymphoma who were included and received rituximab 375 mg/m intravenously (IV) on day 1 and fludarabine 25 mg/m (IV) given on days 1–5 (days 1–3 in > 60 years), every 4 weeks; after the first cycle, oral fludarabine was permitted. After 3 cycles, a work-up was done. Patients in complete remission (CR) received an additional cycle and, if partial remission (PR), a total of 6 cycles. Results: 22 patients were included. Characteristics: median age: 60 years (32–83); 45% male; PS 0–1 (100%); site of lymphoma origin: gastric (61%) and extragastric (39%); stage: I (45%), II1 (23%), II2 (5%) and IV (27%). A total of 101 cycles of RF were administered and 21 pts were evaluable for response. After the third cycle, 13 pts (62%) achieved CR and 8 pts (38%) PR. At the end of therapy, 19 pts (90%) achieved CR and 2 pts (10%) PR. Univariate analysis identified primary extragastric disease as an adverse factor to reach CR after 3 cycles of RF (HR 23.3 (95% CI, 2.0–273.3)). The median follow-up time was 23 months (95% CI, 18–27 months). Progression free survival (PFS) at 24 months was 88 % (95% CI, 80–100%). PFS at 24 months in gastric and extragastric MALT lymphoma were 100% and 79%, respectively. Tolerance to oral fludarabine was excellent. Mild neutropenia was the most common toxicity, usually presenting after the third cycle and 2 pts had prolonged mild thrombocytopenia. No grade 3–4 infections were observed. Conclusions: Immunochemotherapy with RF, either with intravenous or oral fludarabine, achieves a high CR rate in both gastric and extragastric MALT lymphoma, although the firsts responded faster. With only four cycles of RF, two thirds of patients achieves CR. RF is associated with a good safety profile being mild granulocytopenia and thrombocytopenia the main adverse events. The long-term benefit of this therapy will require prolonged follow-up.

In Multiple Myeloma Progression Free and Overall Survival in the Relapsed Setting Remains Poor with Early Exposure to Novel Agents: Experience from a Real-World Cohort

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4261-4261 ◽  
Author(s):  
Christopher P. Venner ◽  
Nizar J Bahlis ◽  
Paola Neri ◽  
Irwindeep Sandhu ◽  
Peter Duggan ◽  
...  
Keyword(s):  
Research Funding ◽  
Response Rate ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
First Relapse ◽  
Third Line ◽  
Line Of Therapy

Abstract Introduction: With the widespread adoption of novel agents (NA) in all lines of therapy patients are being exposed to both proteosome inhibitors (PIs) and immunomodulatory drugs (IMiDs) early in their treatment course. This has lead to marked improvements in survival in the frontline setting. Data is limited with respect to patient outcomes after exposure to both these drug classes in the real world setting. Here we present our experience examining outcomes after each line of therapy whereby bortezomib-based induction followed by lenalidomide-based therapy at first relapse has become the standard of care. We further explored the outcomes of patients who were exposed to both active classes of drugs within their first 2 lines of therapy. Patients and methods: This series includes patients seen through the provincial Alberta Myeloma and Dysproteinemia Program in Canada. Only patients treated between 2005-2013 were included to allow at least 2 years of follow-up beyond first line therapy. Only those treated with a NA-containing regimen as part of their first line treatment were examined. The cohort was split based on eligibility for autologous stem cell transplant (ASCT). Double exposed patients were those who had been treated with, but were not necessarily refractory to both an IMiD and PI within the first 2 lines of treatment. Outcomes were measured after first, second and third line therapy. Survival outcomes were measured in months (m). OS was measured from the start of each line of therapy until death or last follow-up. PFS was from the start of each line of therapy to relapse, death or last follow-up. Response was measured as per the most recent International Myeloma Working Group criteria. Near complete response (nCR) was used when the monoclonal protein disappeared on protein electrophoresis but was not confirmed by immunofixation. Results: Two hundred forty eight patients had received upfront therapy (non-ASCT = 113 and ASCT = 135). One hundred twenty seven had received second line therapy (non-ASCT = 62 and ASCT = 65). Sixty-four had received third line therapy (non-ASCT = 31 and ASCT = 33). The median OS and PFS after each line of therapy are shown in table 1. After first line therapy the OS (p < 0.001) and PFS (p< 0.001) were significantly better in the ASCT cohort. There were no significant differences in survival outcomes based on transplant eligibility in subsequent lines of therapy (figure 1A and B). The overall response rate to third line therapy was 45% (VGPR = 14% and nCR = 7%) for non-ASCT patients and 52% (VGPR = 15% and nCR = 6%) for ASCT patients. Fifty-five percent of non-ASCT patients failed to respond during third line therapy (34% with progressive (PD) and 21% with stable disease (SD)). Forty-eight percent of ASCT patients failed to respond (PD = 27% and SD = 21%). Forty-seven patients were double exposed within the first 2 lines of therapy (non-ASCT = 26 and ASCT = 21). In this cohort, the OS and PFS after double exposure (i.e. third line therapy) was 15m and 5m respectively with no significant difference based transplant eligibility (figure 1C and D). The response rate to third line therapy was 46% (VGPR = 17% and nCR = 8%) for ASCT patients and 43% (VGPR = 14% and nCR = 5%) for non-ASCT patients. Fifty-five percent failed to respond (PD = 38% and SD = 17%) in the non-ASCT group. Fifty-seven percent failed to respond (PD = 38% and SD = 19%) in the ASCT group. Summary: The introduction of NAs earlier in the management of patients with myeloma has improved OS. This is driven by improvements in PFS to frontline therapy and after first relapse. However, with current therapeutic approaches patients will be exposed to both IMiDs and PIs much earlier in their disease. In many jurisdictions, the limited treatment options in third line and beyond, especially in double exposed patients, poses a significant therapeutic challenge. Durable responses are limited in this setting with most patients relapsing after only 6 months. In addition, approximately a third of patients have overtly progressive disease. Interestingly, front-line ASCT eligibility had no impact on outcome with subsequent relapses, emphasizing the fact that ASCT only improves the outcome for the line in which it is employed. Further study regarding resistant mechanism and clonal evolution after exposure to both IMiDs and PIs will be important in developing rationally designed therapeutic regimens for this population. Disclosures Venner: J&J: Honoraria, Research Funding; Amgen: Honoraria; Celgene: Honoraria, Research Funding. Off Label Use: Some patients in this series will have received frontline lenalidomide which is not yet an approved indication for this drug in Canada.. Bahlis:Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Consultancy; Amgen: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Johnson & Johnson: Research Funding. Neri:Celgene: Research Funding. Sandhu:Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Duggan:Jansen: Honoraria; Celgene: Honoraria. Belch:Janssen-Cilag: Consultancy. Jimenez-Zepeda:Celgene: Honoraria; J&J: Honoraria; Amgen: Honoraria.

Clinical experience with sunitinib (SU) in patients over age 65 with metastatic gastrointestinal stromal tumors (GIST): A retrospective study from the French Sarcoma Group (FSG).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10546-10546 ◽  
Author(s):  
Florence Duffaud ◽  
Isabelle Ray-Coquard ◽  
Frederic Marchal ◽  
Loic Chaigneau ◽  
Olivier Bouche ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Positive Impact ◽  
Univariate Analysis ◽  
First Line ◽  
Hand Foot Syndrome ◽  
Specific Outcome ◽  
Grade 3 ◽  
Ecog Ps ◽  
Dose Reductions

10546 Background: Elderly GIST patients (pts) represent a consistent portion of all GIST pts, but are under-represented in clinical trials. Data on benefits, tolerance of SU in elderly GIST pts and their specific outcome are very limited. Methods: Charts of elderly pts (≥ 65 yrs)treated with SU in routine clinical practice from 11 Centres of the FSG were reviewed to evaluate the efficacy and safety of SU. Results: 71 elderly GIST pts were reviewed, with a median age of 74, [distributed as 65-74, n=36; 75-84, n=30; ≥ 85, n=5], 41 (57%) men, with median ECOG-PS= 1 (0-2), and median active comorbities of 1 (0-4). SU was administered after progression on first-line Imatinib (400 mg/d for 21 pts, 400 then 800 mg/d for 45 pts) or masitinib (5 pts). SU was started at 50 mg/d 4-wks-on/2 wks-off in 37 pts (52%), at 37.5 mg daily in 32 pts (45%), and at 25 mg daily in 2 pts. All but 2 pts experienced at least one adverse event (AE). Drug related AE were mainly of grade 1 or 2 (298/388, 76%), and medically manageable. Most frequent AE were fatigue (20%), diarrhea (11%), mucositis (7%), abdominal pain (7%), hand-foot syndrome (6%), neutropenia (6%), and hypertension (5%). Permanent dose reduction was reported in 33 pts (46%). In 17 pts (24%) SU was permanently stopped due to grade 3 or 4 AE. ; this occurred within 3 months after starting SU in 10 pts. At a median 36 months follow-up, 53 pts progressed, and 28 pts were alive. The median PFS and OS were 10.2 (0.2-54) and 21 (0.5-77) months, respectively. Univariate analysis showed that age (≤ 80), PS (<1), WBC (≤ 4 Giga/l), Hb and Albumin have a positive impact on OS (all p < 0.04) and PFS (all p < 0.05). In multivariate analysis, Albumin and Hb had an impact on OS and PFS, PS had an impact only on OS, and WBC only on PFS. A correlation was found between comorbidities and Grade 3/4 toxicities, but no correlation between any toxicities and outcome. Conclusions: Compared to data from clinical trials, SU yields similar rates of GIST control and OS in elderly pts despite frequent dose reductions or interruptions. Since comorbidities may increase the risks of AEs, careful follow-up to assess tolerance is particularly indicated in elderly GIST pts.

Phase II study of S-1 plus irinotecan (SIR) in patients with advanced colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13508-13508
Author(s):  
A. Goto ◽  
Y. Yamada ◽  
Y. Shimada ◽  
K. Shirao ◽  
T. Hamaguchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Response Rate ◽  
Dose Intensity ◽  
First Line ◽  
Eligibility Criteria ◽  
First Line Therapy ◽  
Highly Active ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
Ecog Ps

13508 Background: Infusional fluorouracil and leucovorin (5-FU/LV) plus irinotecan is one of the standard regimens for the treatment of metastatic colorectal cancer (MCRC). S-1, a combination of tegafur, 5-chloro-2,4-dihydroxypyridine, and oxonic acid, is an oral DPD inhibitory fluoropyrimidine shown to be very effective as first-line treatment for MCRC. The response rate with S-1 was 35–40% in patients with chemo-naïve MCRC. This study evaluated the efficacy and toxicity of S-1 plus irinotecan (SIR). Methods: Eligible patients had untreated MCRC as confirmed histologically, PS 0–1, adequate organ function, and provided written informed consent. First-line SIR was given in 3-week treatment cycles: intravenous irinotecan 150 mg/m2 (day 1) and oral S-1 40 mg/m2 twice daily for 14 days followed by 7 days of rest. Results: Forty-one patients were enrolled; 40 fulfilled all eligibility criteria, and 1 had double cancers. There were 28 men; median age 60 years (range, 23–74); ECOG PS 0/1, 35/6. The overall response rate was 63% (95%CI, 48–78%). Five patients had a CR, 20 a PR, 11 SD, and 2 PD. Median TTP was 8.0 months (range, 1.4–13.8 months); MST was not reached. The most frequent grade 3/4 toxicities included: neutropenia (17%), diarrhea (15%), and anorexia (12%). One patient had Grade 4 constipation. The relative dose intensity of irinotecan was 84%, and that of S-1 was 79%. Dose reduction of irinotecan was required in 41 of 327 administered cycles, and that of S-1 was required in 15 of 327. Conclusions: SIR is a highly active and convenient first-line therapy for MCRC, with an acceptable toxicity profile. S-1 has the potential to replace infusional 5-FU/LV plus irinotecan for MCRC. No significant financial relationships to disclose.

Results of a phase II trial of cetuximab+XELIRI as first-line therapy of patients with advanced and/or metastatic colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13502-13502
Author(s):  
T. H. Cartwright ◽  
P. Kuefler ◽  
A. Cohn ◽  
W. Hyman ◽  
K. A. Boehm ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Stage Iv ◽  
First Line ◽  
Patient Request ◽  
Prior Therapy ◽  
First Line Therapy ◽  
Stage Iv Disease ◽  
Grade 3 ◽  
Ecog Ps

13502 Background: We have previously shown that capecitabine/irinotecan (XELIRI) is effective and well-tolerated in metastatic colorectal cancer (mCRC). Cetuximab targets EGFR and is active in mCRC either alone or combined with chemotherapy. This study evaluated potential improved outcomes with cetuximab+XELIRI in first-line treatment of mCRC. Subjects and Methods: Subjects had histologically confirmed colorectal adenocarcinoma with T4 lesions that were deemed unresectable after preoperative chemoradiation and/or metastatic disease. Treatment: capecitabine 1700 mg/m2 (850 mg/m2 PO BID Days 1–14), irinotecan 200 mg/m2 IV Day 1 every 3 weeks, and weekly cetuximab (initial dose 400 mg/m2 IV over 120 minutes, subsequent doses 250 mg/m2 over 30 minutes). Toxicity was assessed at each visit. Results: Between February and October 2005, 70 subjects enrolled. Baseline characteristics: 43 males (61%), 79% White, median age 61.5 years (range, 32.2 - 85.4), and ECOG PS 0/1= 66%/34%. 63% of subjects had Stage IV disease at diagnosis; 87% of subjects had adenocarcinoma. Prior therapy: surgery (n=60, 86%), chemotherapy (n=14, 20%), and radiotherapy (n=5, 7%). Grade 3–4 treatment-related toxicities in >1 subject included diarrhea (17%); neutropenia and rash (8.5% each); dehydration (7%); nausea/vomiting (5%); and anorexia, dyspepsia, and hypokalemia (3% each). 30 subjects discontinued due to progressive disease (PD) (n=9), toxicity (n=12), MD decision (n=2), patient request/withdrew consent (n=3), death (n=1) and other (n=3; doses delayed >3 weeks). To date 5 subjects have died; no death was treatment-related. Evaluation of tumor responses is ongoing. Conclusions: The combination of cetuximab+XELIRI is feasible and well-tolerated in first-line mCRC. Updated safety and efficacy data will be presented. Funded in part by Bristol-Myers Squibb, Plainsboro, NJ. [Table: see text]

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