A randomized trial of first-line irinotecan/fluoropymidine combinations with or without celecoxib in metastatic colorectal cancer (BICC-C)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3506-3506 ◽  
Author(s):  
C. Fuchs ◽  
J. Marshall ◽  
E. Mitchell ◽  
R. Wierzbicki ◽  
V. Ganju ◽  
...  
Keyword(s):  
Survival Data ◽  
Randomized Study ◽  
First Line ◽  
Double Blind ◽  
Common Grade ◽  
Hand Foot Syndrome ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
Reduced Toxicity ◽  
Better Than

3506 Background: This multicenter, randomized study assessed efficacy & safety for 3 irinotecan/fluoropyrimidines combinations in previously untreated mCRC. In a 3 × 2 factorial design, we also assessed whether celecoxib added to chemotherapy (CT) improved CT efficacy and/or reduced toxicity. Methods: Pts were randomized to: FOLFIRI - irinotecan (I) 180 mg/m2, leucovorin (LV) 400 mg/m2, 5-FU bolus 400 mg/m2, & infusional 5-FU 2400 mg/m2 over 46 hours q 2 wks; modified IFL (m-IFL) - I 125 mg/m2, LV 20 mg/m2, & bolus 5-FU 500 mg/m2 wkly × 2, q 3 wks; or CapeIri - I 250 mg/m2 day 1 & capecitabine 1000 mg/m2 po BID × 14 days, q 3 wks. Pts were also randomized to concurrent celecoxib (400 mg po BID) or placebo in a double-blind fashion. Time to progression (TTP) was the primary endpoint. Results: 430 pts were enrolled from 2/03 to 4/04, prior to an amendment that added bevacizumab to CT arms. Baseline characteristics were balanced. TTP for FOLFIRI (median = 8.2 mos) was significantly better than for either m-IFL (6.0 mos; p = 0.01) or CapeIri (5.7 mos; p = 0.01). Overall survival (OS) also favored FOLFIRI (median = 23.1 mos) compared to either m-IFL (17.6 mos; p=0.10) or CapeIri (18.8 mos; p = 0.19). Common grade ≥ 3 toxicities are listed below. CapeIri had the highest rates of nausea, vomiting, diarrhea, dehydration & hand-foot syndrome, whereas FOLFIRI had lower rates. Among all 430 pts, median TTP did not differ for pts randomized to celecoxib compared to placebo (6.9 vs 6.9 mos; p=0.71). Median OS was also similar for celecoxib vs placebo (19.5 vs 18.8 mos; p=0.63). CT toxicities did not differ for celecoxib vs placebo. Rates for MI/stroke were 1.5% for celecoxib and 1.9% for placebo. Conclusions: First-line FOLFIRI offers a superior TTP when compared to m-IFL or CapeIri; OS & toxicity analyses also favored FOLFIRI. Celecoxib neither improved CT efficacy nor reduced CT toxicity. Updated survival data & data on pts enrolled after the addition of bevacuzimab will be presented. [Table: see text] [Table: see text]

Updated results of BICC-C study comparing first-line irinotecan/fluoropymidine combinations with or without celecoxib in mCRC: Updated efficacy data

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4027-4027 ◽  
Author(s):  
C. Fuchs ◽  
J. Marshall ◽  
E. Mitchell ◽  
R. Wierzbicki ◽  
V. Ganju ◽  
...  
Keyword(s):  
Survival Rate ◽  
Randomized Study ◽  
Progression Free Survival ◽  
First Line ◽  
Double Blind ◽  
Period 2 ◽  
Common Grade ◽  
Grade 3 ◽  
One Year

4027 Background: This multicenter, randomized study assessed efficacy & safety for irinotecan/fluoropyrimidines combinations in previously untreated mCRC. Methods: Pts were randomized to: infusional FOLFIRI, modified bolus IFL (mIFL), or CapeIri; and concurrent celecoxib or placebo in a double-blind fashion. The protocol was amended in April 2004: bevacizumab (bev) was added to the FOLFIRI and mIFL arms, whereas CapeIri was discontinued. Period 1 (P1) and Period 2 (P2) designate subjects enrolled before or after the amendment. Initial efficacy & safety analyses were reported at ASCO ’06. We now report follow-up of 46 months for P1 and 31 months for P2. Results: 430 pts were treated in P1 and 117 pts in P2. Baseline characteristics and post-study treatment were balanced. P1 results: Median progression free survival (PFS) was 7.6 mos for FOLFIRI; 5.9 mos for mIFL (p=0.004); and 5.8 mos for CapeIri (p=0.015). Median overall survival (OS) was 23.1 mos for FOLFIRI; 17.6 mos for mIFL (p=0.087); and 18.9 mos for CapeIri (p=0.27). One-year survival rate favored FOLFIRI (75%) compared to either mIFL (65%) or CapeIri (66%). Overall Response Rate (ORR) was 47% in FOLFIRI, 43% in mIFL, 39% in CapeIri (not significantly different). P2 results: Median PFS was 11.2 mos for FOLFIRI+bev and 8.3 mos for mIFL+bev (p=0.28). Median OS was not reached for FOLFIRI+bev but was 19.2 mos for mIFL+bev (p=0.007). One-year survival rate favored FOLFIRI+bev (87%) when compared to mIFL+bev (61%). ORR was 58% for FOLFIRI+bev and 54% for mIFL+bev (p=0.73). Common grade = 3 AEs are listed below. Celecoxib did not impact safety or efficacy. Conclusions: First line FOLFIRI or FOLFIRI+bev were superior to their comparators and show favorable results in survival and tolerability in untreated mCRC. Median survival for FOLFIRI+bev has not been reached. [Table: see text] No significant financial relationships to disclose.

Safety and efficacy of first-line irinotecan/fluoropymidine combinations in mCRC patients >65 years compared with those ≤65: The BICC-C study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4076-4076 ◽  
Author(s):  
J. Barrueco ◽  
J. Marshall ◽  
E. Mitchell ◽  
R. Wierzbicki ◽  
V. Ganju ◽  
...  
Keyword(s):  
Randomized Study ◽  
Age Groups ◽  
Secondary Analysis ◽  
Progression Free Survival ◽  
First Line ◽  
Double Blind ◽  
Period 2 ◽  
Common Grade ◽  
Grade 3 ◽  
Asco 2006

4076 Background: BICC-C was a multicenter, randomized study that assessed efficacy & safety of irinotecan/fluoropyrimidines combinations in previously untreated mCRC patients. This study showed that FOLFIRI or FOLFIRI+bev were superior to their comparators (Proc ASCO 2006). We conducted a secondary analysis of efficacy & safety among all patients >65 years compared with those =65. Methods: Pts were randomized to: infusional FOLFIRI, modified bolus IFL (mIFL), or CapeIri; and concurrent celecoxib or placebo in a double-blind fashion. The protocol was amended in April 2004 and bevacizumab (bev) was added to the FOLFIRI and mIFL arms whereas CapeIri was discontinued. Period 1 (P1) and Period 2 (P2) designate subjects enrolled before or after the amendment. Results: Of 430 pts enrolled in P1, 150 were age >65 (median 71; range, 66–87) and 280 were = 65 (median, 56; 20–65). Of 117 pts in P2, 75 were >65 (median, 73; 66–84) and 42 were = 65 (median, 54; 32–65). No significant differences in efficacy or safety were observed between the two age groups. Results for P1: median progression free survival (PFS) was 6.5 and 6.7 mos; and median overall survival (OS) was 18.8 and 19.2 for >65 and =65, respectively. For the FOLFIRI regimen specifically median PFS was 7.5 and 7.6 mos, and median OS was 20.1 and 24.3 mos for >65 and =65, respectively. Results for P2: median PFS was 10.3 and 10.6 mos; and median OS was 19.8 and 23 mos for >65 and =65, respectively. For the FOLFIRI+bev regimen specifically median PFS was 11.1 and 11.2 mos for >65 and =65 respectively, and median OS has not yet been reached for either subgroup at time of analysis. Common grade = 3 AEs are listed below. Conclusions: Efficacy and safety for first line irinotecan/fluoropyrimidine regimens and for FOLFIRI & FOLFIRI+bev, specifically, did not differ for older and younger mCRC patients. [Table: see text] [Table: see text]

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.

JUPITER-02: Randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC).

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA2-LBA2
Author(s):  
Rui-hua Xu ◽  
Hai-Qiang Mai ◽  
Qiu-Yan Chen ◽  
Dongping Chen ◽  
Chaosu Hu ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Double Blind ◽  
Grade 3 ◽  
First Line Treatment

LBA2 Background: Gemcitabine-cisplatin (GP) chemotherapy is the standard 1st line treatment for locally advanced, recurrent or metastatic (r/m) NPC. Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, provided durable responses in patients (pts) with r/m NPC as monotherapy in the ≥2nd line setting (POLARIS-02 study). The results of JUPITER-02, a randomized, placebo-controlled, double-blinded Phase III trial of toripalimab in combination with GP chemotherapy as first-line treatment for r/m NPC are summarized. Methods: Pts with advanced NPC with no prior chemotherapy in the r/m setting were randomized (1:1) to receive toripalimab 240 mg or placebo d1 in combination with gemcitabine 1000 mg/m2 d1, d8 and cisplatin 80 mg/m2 d1 every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG PS (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. Progression-free survival (PFS) and response were assessed by independent review committee (IRC) per RECIST v1.1. The primary endpoint was PFS by IRC in the ITT population. Secondary end points included ORR, DOR and OS. There was one prespecified interim analysis of PFS at 130 PFS events with a planned final analysis at 200 PFS events. Results: 289 pts were randomized: 146 to the toripalimab arm and 143 to the placebo arm. By May 30, 2020 as the interim analysis cutoff date, the median treatment duration was 39 weeks in the toripalimab arm and 36 weeks in the placebo arm. A significant improvement in PFS was detected for the toripalimab arm compared to the placebo arm (HR = 0.52 [95% CI: 0.36-0.74] two-sided p = 0.0003), with median PFS of 11.7 vs. 8.0 months. The 1-year PFS rates were 49% and 28% respectively. An improvement in PFS was observed across relevant subgroups, including all PD-L1 subgroups. The ORR was 77.4% vs. 66.4% (P = 0.033) and the median DOR was 10.0 vs. 5.7 months (HR = 0.50 [95% CI: 0.33-0.78]). As of Jan 15, 2021, OS was not mature, with 25 deaths in the toripalimab arm and 35 in the placebo arm (HR = 0.68 [95% CI: 0.41-1.14], P = 0.14). The incidence of Grade ≥3 adverse events (AEs) (89.0% vs 89.5%); AEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%); and fatal AEs (2.7% vs 2.8%) were similar between two arms; however, immune-related (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as 1st-line treatment for pts with advanced NPC provided superior PFS and ORR and longer DOR than GP alone with a manageable safety profile. These results support the use of toripalimab with GP chemotherapy as the new standard care for this population. Clinical trial information: NCT03581786.

Capecitabine As First-Line Treatment for Patients Older Than 70 Years With Metastatic Colorectal Cancer: An Oncopaz Cooperative Group Study

2005 ◽  
Vol 23 (13) ◽  
pp. 3104-3111 ◽  
Author(s):  
Jaime Feliu ◽  
Pilar Escudero ◽  
Ferrán Llosa ◽  
Matilde Bolaños ◽  
Jose-Manuel Vicent ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Combination Chemotherapy ◽  
Clinical Benefit ◽  
Overall Response Rate ◽  
Advanced Colorectal Cancer ◽  
First Line ◽  
Hand Foot Syndrome ◽  
Clinical Benefit Response ◽  
Grade 3

Purpose To determine the tolerability of capecitabine in elderly patients with advanced colorectal cancer (CRC). Patients and Methods Fifty-one patients with advanced CRC who were ≥ 70 years and considered ineligible for combination chemotherapy received oral capecitabine 1,250 mg/m2 twice daily on days 1 to 14 every 3 weeks. Patients with a creatinine clearance of 30 to 50 mL/min received a dose of 950 mg/m2 twice daily. Results A total of 248 cycles of capecitabine were administered (median, five cycles; range, one to eight cycles). The overall response rate was 24% (95% CI, 15% to 41%), including two complete responses (CR; 4%) and 10 partial responses (PR; 20%). Disease control (CR + PR + stable disease) was achieved in 67% of patients. The median times to disease progression and overall survival were 7 months (95% CI, 6.4 to 9.5 months) and 11 months (95% CI, 8.6 to 13.3 months), respectively. Of the 35 patients evaluated for clinical benefit response, 14 (40%; 95% CI, 24% to 58%) showed clinical benefit. Capecitabine was well tolerated. Treatment-related grade 3 and 4 adverse events were observed in only six patients (12%), and the most common events were diarrhea, hand-foot syndrome, and thrombocytopenia. One patient (2%) had an episode of angina, but no treatment-related deaths were reported. Conclusion Our findings suggest that capecitabine is effective and well tolerated in elderly patients with advanced CRC who are considered ineligible for combination chemotherapy.

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.

Randomized double blind (DB) placebo (Plcb) controlled phase III study assessing the efficacy of xaliproden (X) in reducing the cumulative peripheral sensory neuropathy (PSN) induced by the oxaliplatin (Ox) and 5-FU/LV combination (FOLFOX4) in first-line treatment of patients (pts) with metastatic colorectal cancer (MCRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3507-3507 ◽  
Author(s):  
J. Cassidy ◽  
G. A. Bjarnason ◽  
T. Hickish ◽  
C. Topham ◽  
M. Provencio ◽  
...  
Keyword(s):  
Cumulative Dose ◽  
Significant Risk ◽  
Dose Intensity ◽  
Sensory Neuropathy ◽  
Median Number ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Grade 3

3507 Background: X, an orally administered non-peptide neurotrophic agent developed by sanofi-aventis, was shown in vitro to minimize neuritic damage induced by Ox (co-culture of Schwann cells and dorsal roots ganglia explant). The probability of occurrence of Grade (Gr) 3–4 PSN at a cumulative dose of Ox of 1000 mg/m2, was consistently reported to be of 18–20%. Methods: First line MCRC pts were randomized to receive, in a DB fashion, FOLFOX4 and either Plcb or X 1mg daily. X was administered from the 1st day of chemotherapy till 15 days post last Ox cycle. Co-primary objectives were reduction in the risk of occurrence of Gr 3–4 PSN relative to cumulative dose of Ox (Kaplan-Meier method) and non-inferiority in response rate (RR). Secondary endpoints included evaluation of sensory action potential (SAP) and safety. Results: From July 2002 to May 2004, 649 pts were randomized (324 Plcb, 325 X). Pts characteristics were well balanced across arms, median number of Ox cycles was 12 in both arms, median relative dose intensity (%) was 83.8 (Plcb) and 85.2 (X). A significant risk reduction of 39% in the probability of Grade 3–4 PSN in favor of X was reported (hazard ratio [95% CI] = 0.61 [0.40; 0.93], p= 0.0203). Overall RR [95 % CI] was: Plcb 42.6% [37.1; 48.2] and X 44.9% [39.4; 50.6]. As prospectively defined in the protocol, the lower bound of the CI of the RR ratio above 0.8 confirms noninferiority in RR (1.055 [0.88; 1.26]). In both arms the mean % of change in SAP worsens as a function of PSN severity. 17.3 (Plcb) and 13.5% (X) of the pts discontinued Ox because of PSN. Severe toxicities (% Gr 3–4), reported with a ≥2% difference between arms, were (plcb vs X): diarrhea 10.9 vs 13.0, pulmonary embolism 0.9 vs 3.1, fatigue 3.7 vs 1.5, neutropenia 43.0 vs 37.8. Conclusion: X was shown to be efficient in reducing the risk of Grade 3–4 oxaliplatin-induced PSN without impacting FOLFOX4 antitumor activity. No significant financial relationships to disclose.

Sunitinib malate (SU) plus interferon (IFN) in first line metastatic renal cell cancer (mRCC): Results of a dose-finding study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5101-5101 ◽  
Author(s):  
G. V. Kondagunta ◽  
G. R. Hudes ◽  
R. Figlin ◽  
G. Wilding ◽  
S. Hariharan ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Cell Cancer ◽  
Single Agent ◽  
Dose Finding ◽  
First Line ◽  
Sunitinib Malate ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Multitargeted Tyrosine Kinase Inhibitor ◽  
Dose Modifications

5101 Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs and PDGFRs with anti-tumor activity in mRCC patients previously treated with cytokines (JAMA, 2006;295:2516). A phase 3 randomized trial showed superiority for SU over IFN in first-line mRCC (PROC ASCO 24,18S, 2006). Dose and safety for SU combined with IFN was investigated in this phase I trial. Methods: Patients (pts) with previously untreated clear-cell mRCC received SU in repeated 6-week cycles of 50 or 37.5 mg/day orally for 4 weeks, followed by 2 weeks off treatment. IFN was given continuously, starting at 3 MU SC 3x/week with intrapatient dose escalation weekly as tolerated, to a maximum of 9 MU. Pts not tolerating a dose combination received lower doses of SU or IFN, or had dose interruptions. Doses of SU plus IFN were considered tolerable if = 4/6 pts completed 2 cycles without dose reduction or interruption. Results: 25 pts were enrolled; 19 are evaluable for safety/response. 6 pts who started treatment at 37.5 SU and 3 MU IFN are too early. The median age of the 19 pts (16 M: 3 F) was 63 years (range 45–77). MSKCC risk group (JCO 20:289–96, 2002) was 37% good and 63% intermediate. 12 pts started treatment with SU 50 mg and dose escalated IFN to 6 or 9 MU TIW. 13 pts started treatment with SU 37.5 mg and dose escalated IFN at 3 MU or to 6 MU TIW. 4 of 19 pts tolerated two cycles. 68% of pts had dose interruptions of SU; 90% of pts had dose interruptions of IFN. 15/19 pts had grade 3 toxicity, 1 pt had grade 4 hypertension and 1 pt grade 5 toxicity (myocardial infarction). Most common grade 3 toxicities were neutropenia (26%), fatigue (26%), and hand-foot syndrome (16%). Although response was not a primary endpoint, at a median of 3 cycles, there were 2 PR, 14 SD, 2 PD and 1 pt was not evaluable. Conclusions: The adverse events seen with combination SU and IFN in mRCC, neutropenia and fatigue, were similar to those seen with single agent SU and IFN, and resulted in frequent dose modifications and interruptions. The safety and efficacy of 37.5 mg sunitinib and 3 MU IFN is being evaluated. No significant financial relationships to disclose.

Bevacizumab and pegylated liposomal doxorubicin as first-line therapy for locally recurrent or metastatic breast cancer: A multicenter, single-arm phase II trial of the Swiss Group for Clinical Cancer Research (SAKK)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1030-1030
Author(s):  
C. Rochlitz ◽  
C. Spirig ◽  
T. Ruhstaller ◽  
T. Suter ◽  
M. Bühlmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Liposomal Doxorubicin ◽  
Cardiac Toxicity ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Advanced Breast ◽  
First Line ◽  
Hand Foot Syndrome ◽  
Grade 3

1030 Background: Bevacizumab in combination with taxanes has become a standard first-line treatment of advanced breast cancer in some countries, but there is no information on its use in combination with pegylated lipsomal doxorubicin in metastatic breast cancer. Therefore, we performed a multicenter, single-arm phase II trial to evaluate the toxicity and efficacy of pegylated liposomal doxorubicin (PLD) and bevacizumab (B) as first-line treatment in advanced breast cancer. Methods: PLD at a dose of 20 mg/m2 and B at 10 mg/kg were infused on days 1 and 15 of each 4-week cycle for a maximum of 6 cycles. Thereafter, B monotherapy was continued at the same dose until progression or toxicity. Primary endpoint was the occurrence of specific toxic events known to strongly interfere with quality of life, i.e., severe cardiac toxicity, any grade 4/5 toxicity, and selected grade 3 nonhematological toxicities (hand-foot-syndrome, cognitive disturbance, CNS hemorrhage, and mucositis/stomatitis). Secondary endpoints included overall response, progression free survival (PFS), time to treatment failure, and duration of response. Eligibility criteria included documentation of metastatic or inoperable breast cancer; measurable disease according to RECIST; erbB2-negativity; LVEF of ≥ 55%; WHO performance status 0 or 1. The study used a Herndon's two-stage design with 14 and 29 patients for stages 1 and 2, respectively. The promising rate of primary toxicity was <15% and the uninteresting rate >33%. The type I error probability was 5% and the power 80%. Results: The trial had to be stopped prematurely because of toxicity after the enrollment of 41 evaluable patients. Among these patients, 16 (39%) had grade 3 hand-foot syndrome, 1 grade 3 mucositis and 1 grade 4 cardiac toxicity. Thus, a total of 18/41 (44%, exact 95% c.i. 28–60%) of all patients had a primary toxicity. Best overall response rate was 23.3% (exact 95% c.i. 12–39%), median PFS was 7.5 months (95% c.i. 4.6–8.1 months). Conclusions: The combination of 2-weekly PLD and B in advanced breast cancer is surprisingly toxic and only modestly active and should not be further investigated. [Table: see text]

International randomized phase III study of capecitabine (Cap), bevacizumab (Bev), and mitomycin C (MMC) in first-line metastatic colorectal cancer (mCRC): Final results of the AGITG MAX trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4023-4023
Author(s):  
N. C. Tebbutt ◽  
V. Gebski ◽  
K. Wilson ◽  
M. Cummins ◽  
Y. Chua ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Phase Iii ◽  
First Line ◽  
Treatment Regimens ◽  
Intention To Treat ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Low Toxicity ◽  
Grade 3

4023 Background: The addition of Bev to oxaliplatin or irinotecan based doublet chemotherapy has shown benefit in mCRC. Cap± MMC are alternate chemotherapy regimens suitable for patients (pts) who are either unfit for or who do not require initial oxaliplatin/irinotecan. This phase III study compared Cap with Cap Bev and Cap Bev MMC. The aim was to develop a low toxicity regimen suitable for a broad population of pts with mCRC. Methods: Previously untreated pts with unresectable mCRC considered suitable for Cap monotherapy were randomised to arm A Cap (Cap 2000mg/m2/d or 2500mg/m2 d1–14 q21d), arm B Cap Bev (Bev 7.5mg/kg q3w) or arm C Cap Bev MMC (MMC 7mg/m2 q6w). Primary endpoint: PFS, secondary endpoints: RR, toxicity, OS, QoL . Randomisation was stratified by age, PS, centre and Cap dose. Response was assessed every 6w. The study was designed to detect an increase in the median PFS from 5.5m (arm A) to 8m (arm B or C) at p<0.025 with 80% power. Results: A total of 471 pts were randomised from July 2005-June 2007. Outcomes were evaluated on an intention to treat basis and included 15 ineligible pts. Baseline demographics were well balanced between arms with median age 67y (range 31–86y). Toxicity was reported: ASCO 2008 abstr 4029. The most common grade 3/4 toxicities were PPE (16%, 26%, 28%) and diarrhoea (11%, 17%, 16%) for arms (A,B,C). However, adjusted rates per cycle were similar as arms B & C received more cycles of Cap (A8.3, B10.8, C10.5). Other toxicity rates were generally <10%. The study achieved its primary endpoint with a highly significant improvement in PFS for arms B & C. RR and OS are summarized ( Table ). Conclusions: All treatment regimens were well tolerated in a relatively elderly patient cohort. The addition of Bev±MMC to Cap significantly improved PFS without significant additional toxicity. OS was similar for all arms. Cap Bev±MMC is an active, low toxicity regimen that may be considered as a treatment option for pts with mCRC. [Table: see text] [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document