Effect of short-duration chemoimmunotherapy plus radioimmunotherapy on response rates in relapsed follicular lymphoma: A U.K. NCRI Lymphoma Group Study, CR UK/07/038.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8056-8056
Author(s):  
Timothy M Illidge ◽  
Andrew T. Bates ◽  
Andrew John Davies ◽  
Ruth Pettengell ◽  
Barry Andrews ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Median Duration ◽  
Overall Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
First Line ◽  
Ibritumomab Tiuxetan ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Kidney Liver

8056 Background: Radioimmunotherapy (RIT) and rituximab (R) maintenance have been investigated after chemotherapy (CT) or R-CT in first line treatment of follicular lymphoma (FL), but less is known about the efficacy of RIT after R-CT in relapsed FL. This phase II study was conducted to examine efficacy and safety of abbreviated R-CT followed by 90Y Ibritumomab tiuxetan in patients with recurrent FL. Methods: Patients (pts) had FL, at 1st or 2nd relapse after response to R-CT or CT alone. All had WHO/ECOG performance status ≤2, and adequate bone marrow (BM), kidney, liver and cardiac function. BM involvement by lymphoma had to be <25% prior to infusion of 90Y Ibritumomab tiuxetan, but could be higher at study entry. Pts received 3 cycles of either R-CHOP or R-CVP, followed by 90Y Ibritumomab tiuxetan (15MBq/Kg, maximum 1200 MBq). No maintenance R was given. Results: 52 pts were enrolled from 6/2008 to 7/2010. Median age was 62 years (range 31-87). 46% had high FLIPI score at entry, 31% intermediate. 80% were at 1st recurrence. Median duration of best prior remission was 27.7 months. 65% pts had previously received R and 25% doxorubicin. 71% pts had R-CHOP and 29% R-CVP, prior to RIT. Overall response rate (ORR) after 3 cycles R-CT was 94% (CR/CRu 10%) and after RIT ORR 96% (CR/CRu 28%). Grade 3/4 thrombocytopenia occurred in 58% pts (median duration 16 days): 3/52 pts after R-CT and 27/52 after RIT. Grade 3/4 neutropenia occurred in 62% pts: 15/52 pts after R-CT and 27/52 after RIT. 5 pts had a total 8 grade 3 infections, only 1 attributable to RIT. 6 pts required platelets and 4 red cell transfusions. 1 pt developed myelodysplasia 10 months after 90Y Ibritumomab tiuxetan, but no other second malignancy was recorded. PFS was 31.4 months (95% CI 15.8 - not reached). There was no difference in PFS according to FLIPI score at entry or reinduction CT (R-CHOP vs R-CVP). Pts with CR/CRu following RIT showed a trend to improved PFS compared to those with PR (12 month PFS 90% versus 63%, p=0.06). Conclusions: Abbreviated R-CT and consolidation with 90Y Ibritumomab tiuxetan is an option for pts with recurrent FL, with responses of comparable duration to those seen after a full course R-CHOP.

Pemetrexed (MTA) and carboplatin (CBDCA) in the treatment of advanced pleural mesothelioma (MPM)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7093-7093 ◽  
Author(s):  
B. Castagneto ◽  
M. Mencoboni ◽  
D. Degiovanni ◽  
A. Muzio ◽  
L. Giaretto ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Entire Group ◽  
Hematologic Toxicity ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

7093 Background: Aim of this study was to evaluate the activity and toxicity of MTA and CBDCA combination as first line chemotherapy in advanced MPM. Methods: Chemonaive patients (pts) with histologically proven, an ECOG performance status (PS) 0–2, and measurable advanced MPM were considered. The schedule of administration was: pemetrexed 500 mg/m2 in combination with CBDA AUC 5, once every 21 days for 8 cycles. Results: From July 2003 to March 2005 76 pts (54 male and 22 female) have been treated with this combination chemotherapy. Median age was 62.7 years (range 40–70); median PS 0 (range 0–3); epithelial histologic findings were in 57 (75%), mixed in 13 (17.1%), sarcomatous in 3 (3.9%), and unspecified in 3 (3.9%) pts. A total of 537 cycles was administered (median 7, range 1 to 13). Grade 3 hematologic toxicity according to WHO criteria was seen in 43 (56.6%) pts (neutropenia in 30, thrombocytopenia in 8, and anemia in 5); grade 4 hematologic toxicity in 5 (6.6%) pts. The most common nonhematologic events were grade 3 nausea/vomiting in 10 (13.1%), and fever in 4 (5.3%) pts. 74 pts were evaluable for clinical response. There were 16 (21.%) partial responses (PR) and 3 (3.9%) complete responses (CR), for an overall response rate of 23.9%. 29 (38.2%) pts reported stable disease (SD). The overall survival was considered from date of diagnosis to date of death from any cause or to date of last follow-up. The median survival time for the entire group was estimated at 23 months. Conclusions: The results of this phase II study indicate that, at this dose and schedule, the combination of CBDCA and MTA is moderately active and that the profile of toxicity is acceptable in pts with advanced MPM. No significant financial relationships to disclose.

First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9000-9000
Author(s):  
Martin Reck ◽  
Tudor-Eliade Ciuleanu ◽  
Manuel Cobo ◽  
Michael Schenker ◽  
Bogdan Zurawski ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Performance Status ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Expression Level ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]

Combination Of Ofatumumab and Bortezomib In Patients With Indolent B-Cell Lymphomas Who Relapsed >6 Months After Rituximab-Containing Regimen: A Brown University Oncology Research Group Phase II Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5121-5121
Author(s):  
Jorge J Castillo ◽  
James N Butera ◽  
Eric S Winer ◽  
Frederick Lansigan ◽  
Kayla Rosati ◽  
...  
Keyword(s):  
B Cell ◽  
Stable Disease ◽  
Interim Analysis ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Low Grade ◽  
Ecog Performance Status ◽  
Progression Of Disease ◽  
Grade 3

Abstract Introduction Based on the activity of ofatumumab in patients with indolent B-cell non-Hodgkin lymphoma (NHL) and the potential synergistic effect of bortezomib in combination with anti-CD20 antibody therapy, a phase II study to investigate the effect of the combination of ofatumumab and bortezomib in patients with relapsed indolent B-cell NHL who relapsed >6 months after receiving a rituximab-containing regimen was initiated. Methods Patients 18 years or older with a pathologically confirmed low-grade B-cell NHL who relapsed >6 months after a rituximab-containing regimen were included in our study. Other inclusion criteria were ECOG performance status <2, and adequate organ function (creatinine <2 mg/dl, total bilirubin <1.5x ULN, and liver transaminases <2.5x ULN) and bone marrow reserve (neutrophils >0.75, and platelets >50,000/uL). Exclusion criteria included HBV+, HIV+, transformed lymphoma, primary cutaneous lymphoma, central nervous system involvement, <6 months expected survival, and active infection. Treatment consisted of ofatumumab 1,000 mg IV and bortezomib 1.6 mg/m2 IV given weekly for 4 weeks (induction), then every 2 months (maintenance) to complete 12 months of therapy. Valacyclovir or acyclovir was given for herpes zoster prophylaxis while on bortezomib. Acetaminophen, diphenhydramine and glucocorticoids were administered prior to ofatumumab infusions. Response was assessed based on the Cheson criteria (2007). A sample size of 44 patients was planned, and an interim analysis after enrollment of 10 patients was undertaken to evaluate safety and early efficacy. Results We present data on 10 patients enrolled between October 2010 and April 2013. Median age was 66 years (range 55-93 years); eight patients (80%) were 60 years or older. There were 7 (70%) men and 3 (30%) women. LDH was elevated in 8 patients (80%). ECOG performance status was 0 in 9 (90%) and 1 in 1 patient (10%). Six patients (60%) had a histological diagnosis of follicular lymphoma, 1 (10%) mantle cell lymphoma, 1 (10%) small lymphocytic lymphoma, 1 (10%) marginal zone lymphoma, and 1 (10%) low-grade B-cell lymphoma, not otherwise specified. Stage III/IV was seen in 5 patients (50%). Eight patients (80%) had a high-risk FLIPI score. Median time from initial diagnosis to current therapy was 65 months (range 20-204 months). Median time from last rituximab-containing regimen was 24 months (range 11-48 months). Median number of previous therapies was 2 (range 1-4). Three patients (30%) had previously received radiotherapy. One patient (10%) had previously undergone autologous stem cell transplantation. Response rates after induction therapy were: 1 (10%) complete response (CR), 3 (30%) partial response (PR), 3 (30%) stable disease, 1 (10%) progressive disease, and 2 (20%) not evaluable for response. With exception of 1 patient who continues on therapy, the patients who achieved a response or had stable disease after induction therapy showed progression of disease during maintenance. Median duration of response in patients who responded was 4 months (range 1-9 months). At the time of this report, 7 patients (70%) are alive with disease, 2 (20%) are alive without evidence of disease, and 1 (10%) has expired. Five grade 3 or 4 adverse events (AEs) occurred; grade 4: diarrhea (n=1) and hyperglycemia (n=1); grade 3: infusion reaction (n=1), nausea (n=1) and rash (n=1). No grade 3 or 4 peripheral neuropathy or hematological AEs were observed. The most common grade 1 or 2 AEs were: infusion reactions (n=6), anemia (n=5), thrombocytopenia (n=5), fatigue (n=4), diarrhea (n=4), hyperglycemia (n=4) and lymphopenia (n=4). No deaths have occurred while on therapy. Conclusions The combination of ofatumumab and bortezomib given weekly for 4 weeks induced a response in 40% and stable disease in 30% of the patients. However, most of the patients experienced progression of disease during the maintenance phase of the study. Furthermore, there were five grade 3 or 4 AEs associated with therapy. Based on this interim analysis, it was decided to stop enrollment. The combination of ofatumumab and bortezomib, however, appears potentially active and deserves further study. Different schemas of therapy with longer induction or different maintenance schedule could prove to be safer and more effective. Disclosures: No relevant conflicts of interest to declare.

Prospective phase II trial of a combination of gemcitabine, cisplatin and UFT as first-line treatment in patients with advanced, unresectable, non-small cell lung carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18109-18109
Author(s):  
S. S. Jin ◽  
Y. Min ◽  
H. Kim ◽  
J. Ahn ◽  
Y. Jegal ◽  
...  
Keyword(s):  
Survival Time ◽  
Overall Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Performance Status ◽  
Small Cell ◽  
Time To Progression ◽  
Small Cell Lung ◽  
First Line ◽  
Grade 3

18109 Background: Most patients with advanced non-small cell lung cancer (NSCLC) receive either single agents or doublet chemotherapy. For non-elderly patients in good performance status, platinum-based double combinations represent the standard treatment. And oral UFT had the survival advantage in adjuvant setting. Therefore we performed a phase II study using the combination of gemcitabine, cisplatin and UFT as a first line therapy in patients with advanced NSCLC. Methods: Eligible patients had histologically or cytologically confirmed stage IIIB or IV NSCLC with good performance status and were chemotherapy-naive. This study was two-stage design and planned number of patients was forty-seven. Gemcitabine (1,250 mg/m2, 10 mg/kg/min on days 1 and 8) and cisplatin (75 mg/m2 on day 1) were injected intravenously and UFT (400 mg/day) was administered orally on day 1–14. Treatment repeated every 3 weeks. Primary end point was overall response rate and secondary end points were overall survival, time to progression and toxicity. Results: Thirty seven patients with advanced NSCLC were enrolled. The median age of the patients was 60 years (range: 44 to 72). The performance status (WHO) was 0 in 4, 1 in 30 and 2 in 3 patients. Twenty three patients completed six cycles. Complete response was achieved in 1 (3%) patient, partial response in 22 (59%) patients, stable disease in 9 (24%) patients. Overall response rate was 62% on intent to treat basis. Among patients who response evaluation was possible (33 patients), response rate was 70%. The median survival time was 14.5 months (95% CI 6.9, 22.3) and the 1 year survival was 35% and then median time to progression was 3.4 months(95% CI 3, 3.9). Toxicities were moderate and mostly hematological adverse events. Grade 3/4 neutropenia occurred in 37%, 5 patients with febrile neutropenia. Grade 3/4 anemia and thrombocypenia was occurred in 37% and 5%. Nonhematologic toxicities were mild. Conclusion: The combination therapy consisted of gemcitabine, cisplatin and UFT is active and well tolerable first line regimen for NSCLC patients. No significant financial relationships to disclose.

Phase II study of bortezomib with cisplatin as first-line treatment of malignant pleural mesothelioma (MPM): EORTC 08052.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7081-7081 ◽  
Author(s):  
Mary O'Brien ◽  
Rabab Mohamed Gaafar ◽  
Sanjaykumar Popat ◽  
Francesco Grossi ◽  
Allan Price ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Dose Intensity ◽  
Line Treatment ◽  
First Line ◽  
Phase Ii Studies ◽  
Grade 3 ◽  
First Line Treatment

7081 Background: Cisplatin is one of the most active drugs available in MPM while bortezomib has shown some activity in single agent phase II studies against MPM. This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of MPM. Methods: Patients with histological proven MPM, with performance status (PS) 0/1, were eligible. The doses were cisplatin 75mg/m2 /3 wks and bortezomib 1.3mg/m2 day 1, 4, 8, 11 every 3 wks. The primary end-point was progression free survival rate at 18 wks (PFSR=18). The 2-stage Simon design (a=0.1; b = 0.05, P0=0.50 and P1=0.675) was used. In the first step of the study 37 eligible patients were planned. If more than 19 patients were alive and free of progression at 18 wks the total sample size was increased to 76 eligible patients. Results: Between 2007 and 2010 82 patients were entered. The median follow-up time is 32.3 months The median age was 55 years (range: 22-77yrs), male/female: 55/27 , PS 0/1: 9/73, Stage T1: 10%; T2: 42%, T3: 25%; T4: 23% and N0: 57%; N1: 4%; N2: 33%; N3: 6%. The median number of cycles received was 4 and 38% received 6 cycles. Cisplatin/ bortezomib dose intensity was 98/ 80%. Toxicity (grade 3/4): neutropenia 10%, thrombocytopenia 11%, anaemia 1%. Grade 3-4 hyponatraemia/ hypokalaemia occurred in 46/ and 17%. Grade 2 tinnitus, grade 3 fatigue occurred in 16%, and 12%, of patients. Motor/sensory/other neurotoxicity was grade 1: 6/28/7%, grade 2: 2/26/2% and grade 3: 1/7/2% respectively. There were 2 toxic deaths at 32 and 74 days due to acute pneumonitis and cardiac arrest. The PFRS-18 (including symptomatic progression) was 53% (80% confidence intervals, CI, 42-64%). The overall survival was 13.5 months (95% CI 10.5-15) with 56% (95% CI 44-66%) alive at 1 year. The PFS was 5.1 months (95% CI 3.3-6.5). Conclusions: On the basis of the PFRS-18, the null hypothesis could not be rejected, although CB gave predictable toxicity and was as active as other reported regimens in MPM.

Phase II study of PX-866 in recurrent glioblastoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2053-2053 ◽  
Author(s):  
Marshall W. Pitz ◽  
Elizabeth A. Eisenhauer ◽  
Mary Valeria MacNeil ◽  
Brian Thiessen ◽  
David R. Macdonald ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Recurrent Glioblastoma ◽  
Pik3ca Mutations ◽  
Overall Response ◽  
Grade 3

2053 Background: Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system. The majority have genetic changes that increase the activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway, critical for cell motility, proliferation, and survival. We present the results of PX-866, an oral PI3K inhibitor, in patients (pts) with recurrent GBM. Methods: A multinomial design of response and early progression (< 8 weeks on study) was used. In stage 1 (15 pts), 0 responses and ≥ 10 early progressions would stop accrual; after full accrual, ≥ 4 responses OR ≤ 13 early progressions was prespecified as of interest. Pts with histologically confirmed GBM, at first recurrence after chemoradiation and adjuvant temozolomide were given PX-866 8 mg daily on this single-arm phase II study. MRI and clinical exam were done every cycle (8 weeks). Tumour tissue was collected for analysis of potential markers of PI3K inhibitory activity (PTEN, EGFRviii, PIK3CA mutations). Results: A total of 33 pts were enrolled, eligible and evaluable. Median age was 56 (range 35-78), 12 were female; 29 had performance status (PS) 0-1 and 4 had PS 2. Median time from initial diagnosis to enrolment was 308 days (range 141-1256). Median number of cycles was 1 (range 1-7). Thirty-two pts have discontinued therapy, 26 due to disease/symptomatic progression and 6 due to toxicity (5 LFT elevation and 1 allergic reaction). Other adverse effects (AE): fatigue (16 pts/2 grade 3), diarrhea (11 pts/5 grade 3), nausea (19 pts/1 grade 3), vomiting (11 pts/1 grade 3) and lymphopenia (29 pts/7 grade 3/4). Five pts had related serious AEs (1 LFTs, 1 GI and 3 venous thromboembolism) All pts were evaluable for response; 25 had a best response of progression, 1 had partial response (overall response rate 3%) and seven (21%) had stable disease (SD, median 7.3 months; range 3.1-13.6). Six month PFS was 17%. In preliminary analyses, no statistical association was found between SD and PTEN or EGFRviii status (results pending in 16 pts). Conclusions: PX-866 was relatively well tolerated. Overall response rate was low, and the study did not meet its primary endpoint; however, 21% of pts obtained durable stable disease. Further correlative work is required to identify the predictor of this effect. Clinical trial information: NCT01259869.

Phase II study of pazopanib with weekly paclitaxel in refractory urothelial cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 294-294 ◽  
Author(s):  
Sandy Srinivas ◽  
Sujata Narayanan ◽  
Lauren Christine Harshman ◽  
Russell Kent Pachynski ◽  
Anthony P. Lam ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Median Number ◽  
Upper Urinary Tract ◽  
Weekly Paclitaxel ◽  
Moderate Activity ◽  
Ecog Performance Status ◽  
Grade 3

294 Background: Currently, there are no standard treatments for relapsed or refractory urothelial carcinoma (UC). Discouraging results have been observed in trials evaluating established chemotherapeutics as single agents or in combination regimens. Paclitaxel has moderate activity when used alone and in combination in UC. Pazopanib is active in other solid tumors secondary to its potent anti-angiogenic effects. We report the results of a multi-center phase II study evaluating the combination of paclitaxel with pazopanib in refractory UC. Methods: Eligible patients (pts) had histologically confirmed UC, with disease that progressed on upto 2 chemotherapeutic regimens. Pazopanib (800 mg) was administered daily, with weekly paclitaxel (80mg/m2) for 3 weeks in a 28 day cycle. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of the study was response-rate (RR) based on RECISTv 1.1 criteria. Secondary endpoints included safety, and progression free-survival (PFS). Results: From April 2010 to September 2014, 32 patients were enrolled. Median age was 67 years (29-89) and median ECOG performance status was 1 (0-2). 17 pts (54%) had UC of the upper urinary tract disease and 15(47%) had primary bladder tumors. All pts had multiple metastatic sites, including 9 (28%) with liver metastases. Median number of prior cytotoxic regimens was 2, and 50% were considered cisplatin responsive. Objective responses were observed in 58% with 3 (12%) complete responses (CR), and 12 pts (46%) with partial responses (PR). Another 9 (35%) acheived stable disease (SD). High grade toxicities included grade 3 hypertension (n=2), grade 3 fatigue (n=4), grade 3 thrombosis (n=2) and grade 4 neutropenia (n=2). Nearly half of the patients( n= 14 ) required growth factor support. Conclusions: Our phase II study combining paclitaxel and pazopanib demonstratedsignificant anti-tumor activity in relapsed/refractory UC. This combination is safe, effective and is worthy of evaluation in randomized phase 3 study. Clinical trial information: NCT01108055.

Safety and efficacy of capecitabine (C) plus bevacizumab (B) as first-line in metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1013-1013 ◽  
Author(s):  
G. Sledge ◽  
K. Miller ◽  
C. Moisa ◽  
W. Gradishar
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Primary Objective ◽  
First Line ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Grade 3

1013 Background: C alone has good activity and tolerability in metastatic breast cancer (MBC) and when combined with docetaxel improves response and survival. C combined with B in heavily pretreated MBC improved the response rate but not PFS. In untreated MBC, the addition of B to chemotherapy significantly improves progression-free survival (PFS) which suggests that B, is most effective in early disease. Methods: Primary objective of this single-arm, 2-phase study, is to evaluate PFS in MBC patients receiving first-line treatment with C 1,000 mg/m2 twice daily on days 1–15 (28 doses) and B 15 mg/kg on day 1. Treatment was repeated every 21 days until progression. Eligibility criteria included HER2-negative MBC previously untreated for metastatic disease; ECOG performance status =1; no prior anti-angiogenic or oral fluoropyrimidine therapy. A sample size of 109 patients (including dropouts) was required to give 90% power to test an improvement from 4 months median PFS to 5.6 months with the two-sided test (a 5%) Results: At data cut-off, 103 patients had received study medication. Present results are based on 103 patients (ITT population), except tumor response which is based on 91 patients who had response evaluation. The average # of cycles received in first phase is 6.8. 84 pts.are alive at this time. 38.5% (35/91) pts. have had a response: complete response 5.5%; partial response 33.0%. Stable disease is 42.9% with 81.4% clinical benefit. Planned dose received is 77.7 % for C and 99.0 % for B. The majority of adverse events (AEs) were mild or moderate. The most common grade 3 AEs were hand-foot syndrome (13%) and pain (10%); grade 4 pulmonary embolism occurred in 2% in the first phase of the study. Conclusions: Updated results with longer follow-up including toxicity, TTP and PFS will be presented at the meeting. It appears that in first-line C+B is active for MBC and is well tolerated, with few grade 3/4 toxicities. [Table: see text]

Addition of continuous low dose temozolomide (T) to bevacizumab (Bev) plus irinotecan (Iri) after bevacizumab plus irinotecan failure in heavily pretreated glioblastoma multiforme (GBM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13015-e13015
Author(s):  
S. Stankewitz ◽  
G. Dresemann
Keyword(s):  
Median Duration ◽  
Low Dose ◽  
Performance Status ◽  
Objective Response ◽  
Ecog Performance Status ◽  
Chemotherapeutic Regimen ◽  
Macdonald Criteria ◽  
Phase Ii Studies ◽  
Mri Scans ◽  
Grade 3

e13015 Background: In several phase II studies in relapsed GBM, Bev plus Iri showed impressive objective response rates (>50%) with acceptable toxicity rate, duration of response, however, was moderate. Methods: From April 2007 to October 2008, 35 pretreated patients with confirmed GBM with progressive disease (PD) after Bev (4 mg/kg body weight i.v.) plus Iri (80 mg/m2 i.v.) were treated with additional continuous low dose T (20 mg per day p.o.) while Bev plus Iri were continued. ECOG performance status (PF) was 0 - 2 in all pts. MRI scan was required after 4 weeks and every 6 weeks afterwards. MacDonald criteria were used for evaluation of response. If MRI scans could not be performed, patients were considered to have PD. Treatment was given until PD or intolerable toxicity occurred. Results: All 35 patients were eligible for toxicity and efficacy, median follow up was 7 months (2 - 20), 25 patients were male, 10 female, median age was 51 years (29 - 80), 21 patients had primary GBM, 14 patients secondary GBM. All patients had prior irradiation (56 - 60 Gy) 2 patients had 5, 8 patients had 4, 15 patients had 3, and 10 patients 2 prior chemotherapeutic regimen. 1 patient developed grade 3 leucopenia, and 1 patients grade 3 thrombopenia; 3 patients asymptomatic intracerebral bleeds requiring treatment delay, 1 pat. grade 3 sepsis and 2 patients grade 3 fatigue. In 4/35 patients a partial response (PR) was achieved, in 14/35 patients a disease stabilization for at least 2 months, while 17/35 patients showed primary PD. Median duration of PR was 3.5 months (2–5), median duration of SD was 5 months (2–13), Median survival was 5 months (2–13). Data will be updated. Conclusions: The addition of continuous low dose T in combination with Bev plus Iri seems to have activity in GBM patients, after progression on Bev plus Iri treatment, and has an acceptable toxicity profile. Further investigation of the combination Bev plus Iri plus T in GBM patients is necessary. No significant financial relationships to disclose.

Cetuximab plus docetaxel-cisplatin (DC) as first-line treatment for locally advanced or metastatic gastric cancer: Preliminary results of a phase II study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15592-e15592
Author(s):  
J. Fahlke ◽  
K. Ridwelski ◽  
A. Florschuetz ◽  
E. Kettner ◽  
M. Leithaeuser ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Disease Progression ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Published Data ◽  
First Line ◽  
Overall Response ◽  
Grade 3

e15592 Background: Based on promising published data, this multicenter, phase II study was initiated to investigate a combined treatment using DC and cetuximab in the first-line setting for patients with gastric cancer. Methods: Patients aged 18–75 years with stage III (T4, nonresectable) or stage IV gastric cancer, ECOG performance status (PS) ≤2, and life expectancy ≥3 months were recruited to receive cetuximab (400 mg/m2 on day 1 then 250 mg/m2 q1w) and DC (D 75 mg/m2 and C 75 mg/m2; both as 1-h infusions on day 1 and then q3w). Treatment was stopped in the event of disease progression, intolerable toxicity, or consent withdrawal. Tumor staging was performed after cycle 3 and then every 12 weeks. The primary endpoint was overall response rate and secondary endpoints included time to progression, overall survival and toxicity. Planned accrual was 79 patients. A per-protocol interim response analysis was planned for the initial 20 evaluable patients. Results: Preliminary data are available for 30 patients; median age 64 [range: 40–73] years; median ECOG PS 1 [range: 0–2]; adenocarcinoma 87%. Median cycles administered were 3 [range: 1–14] and the median follow-up was 1.63 months. The overall response rate was 27.3% (complete response, n=1; partial response, n=5). Stable disease was observed in 10 patients, and disease progression in 6 patients. The most relevant NCI-CTC grade 3–4 hematologic events per patient were leukopenia and neutropenia (73%), anemia (13%), and febrile neutropenia (10%). Major grade 3–4 nonhematologic toxicities were nausea (30%), vomiting (20%), diarrhea (13%), acne (13%), and fatigue (13%). Conclusions: DC and cetuximab were well tolerated and resulted in promising response rates and a predictable toxicity profile. The study is ongoing. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document