Gemcitabine/nab-paclitaxel (G/A) alternating with 5-FU/leucovorin/irinotecan (FOLFIRI) in first-line metastatic pancreatic cancer (MPC): Updated results.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 314-314
Author(s):  
Vincent J. Picozzi ◽  
Bruce Shih-Li Lin ◽  
Margaret T. Mandelson
Keyword(s):  
Cancer Biology ◽  
De Novo ◽  
Median Number ◽  
First Line ◽  
Disease Treatment ◽  
Patient Decision ◽  
Disease Site ◽  
Grade 3 ◽  
Ecog Ps ◽  
Physician Patient

314 Background: Both gemcitabine- and 5-FU-based chemotherapy (chemoRx) have demonstrated efficacy in MPC. Alternating these two regimens may 1) decrease toxicity 2) slow emergence of resistant cancer biology, and 3) provide a broader platform for addition of other (non)chemotherapeutic (CT) agents to the base regimen. The strategy using alternating G/A and FOLFIRI in MPC was first tested in the SEENA-1 trial (Picozzi et.al. GI Cancer Symposium 2017) and further suggested to be of benefit both at our own institution (Picozzi et.al. ASCO 2018 ) and elsewhere (Assenat et.al. ASCO 2018). We extend and update our observations here. Methods: Eligible patients (pts) had the following characteristics: 1) bx proven de novo MPC, 2) chemoRx naive, 3) ECOG PS 0/1, and 4) bi-dimensionally measurable disease. Treatment (Rx) consisted of 1) gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/2d 1,(8),15 alternating every 8 weeks (2 cycles) with FOLFIRI. Pts were radiographically restaged every 8 weeks. Rx was continued for up to 48 weeks, at which time additional Rx was given per physician/patient decision. Results: As of 9/2018, 61 pts have been treated at our institution via this method. Median age is 67; ECOG PS 0/1 58/42%. Disease site involvement included liver, lung, peritoneum 79%, 39%, and 23% respectively. Toxicity is less than typical with either individual regimen (e.g. no ≥ grade 3 neuropathy or diarrhea has been seen to date). Of pts followed for ≥ 4 months , 45/51 (88%) received ≥ 4 cycles Rx. Median number Rx cycles received was 9; 15/34 (44%) pts followed for > 1 year completed 48 weeks Rx. Disease control rate at 16 weeks in 45 evaluable patients is 89% (47% PR, 42% SD, 11% PD). 27/61 pts (44%) are currently on Rx (4 transferred care from region, 30 deceased). Currently, median f/u is 11.8 mo; median OS is 14.1 mo ( 95% CI 10.6-20.3 mo) 6,12, 18 and 24 mo OS are 88%,57 %, 34%, and 15% respectively. Conclusions: 1) Alternating G/A and FOLFIRI in MPC appears to have a more favorable toxicity profile than either individual regimen. 2) Median OS in MPC using this Rx is at least competitive with other reports. 3) The above method has potential to integrate other therapeutic agents/ treatment approaches.

Preliminary results for the combination of docetaxel, oxaliplatin and capecitabine as a first-line treatment for metastatic oesophagogastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14076-14076
Author(s):  
S. Viteri ◽  
J. Rodríguez ◽  
M. González Cao ◽  
J. De La Cámara ◽  
A. Chopitea ◽  
...  
Keyword(s):  
Performance Status ◽  
Median Number ◽  
New Drugs ◽  
Phase Ii Trials ◽  
First Line ◽  
Ecog Performance Status ◽  
Standard Regimen ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Ecog Ps

14076 Background: Chemotherapy remains the main treatment option for metastatic oesopagogastric cancer (MOC) patients (Pts). First-line regimens have proved a slight but significant increase in quality of life and survival, but a standard regimen has not been defined yet. Several new drugs, as Docetaxel (D), Oxaliplatin (O) and Capecitabine (C) have demostrated activity in MOC. They have shown synergy in preclinical models and activity in previous phase II trials. The purpose of our study is to asses activity and feasibility of the combination of D, O and C as first-line chemotherapy in MOC patients. Methods: MOC patients, with good ECOG performance status and chemonaive are eligible. Pts receive D 60 mg/m2 day 1, O 85 mg/m2 day 1 and oral C 650mg/m2 bid d1–14 every 3 weeks. Primary endpoints are response according to WHO criteria and toxiciy assesment according to NCI.CTCAE v3.0. Results: From November 2004 to December 2005, 17 Pts have been enrolled. Median ECOG PS is 1 (0–2) M/F:9/8. Median age is 57 years (38–68) Primary tumor are gastric carcinomas (82%) and lower oesofagus carcinomas (18%). Metastatic sites included peritoneum 58%, liver 23% and lung 23%. Median number of cycles is 5 (1–7) Treatment is well tolerated with no toxic deaths. NCI grade 3–4 toxicities include 2 Pts (11.8%) with grade 4 neutropenia and one of them developed septic shock; 2 Pts with grade 3 asthenia, 1 Pt with grade 3 vomiting and 1 patient with grade 3 neurotoxicity. Main NCI grade 2 toxicities are dhiarrea (35.3%) and neurotoxicity (23.5%). 13 Pts have been evaluated for response until now: 9 Pts have a confirmed Partial Response (69.2%) and 2 of them underwent salvage surgery; 3 Pts have Stabilized Disease and 1 Pt Progression Disease. Median time to progression and median overall survival have not been reached yet and the study is still ongoing. Conclusions: The combination of D, O and C at the dosses and schedule used in this trial is effective in MOC with a manageable toxicity profile No significant financial relationships to disclose.

Liver resectability following mFOLFOX6 with bevacizumab as the first-line treatment of unresectable liver limited metastases from colorectal cancer in Japanese patients (KSCC 0802).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 666-666 ◽  
Author(s):  
Hironori Samura ◽  
Toru Beppu ◽  
Yasunori Emi ◽  
Yoshihiro Kakeji ◽  
Hiroshi Saeki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Japanese Patients ◽  
Median Number ◽  
Line Treatment ◽  
First Line ◽  
Eligibility Criteria ◽  
Grade 3 ◽  
Multi Center Study ◽  
Ecog Ps ◽  
First Line Treatment

666 Background: There is no data concerning liver resectability following mFOLFOX6 with bevacizumab as the first-line treatment of unresectable liver limited metastases from colorectal cancer by prospective, multi-center study in Japan. The Kyushu Study group of Clinical Cancer (KSCC) conducted a phase II trial in this setting. Methods: Eligibility criteria included unresectable liver limited metastases from histologically confirmed advanced colorectal cancer, ECOG PS 0-1 and adequate general condition. Patients (pts) received 6 cycles of mFOLFOX6 (oxaliplatin 85 mg/m2, l-leucovorin 200 mg/m2 d1 followed by 400 mg/m2 bolus 5-FU and a 46-hr 2,400 mg/m2 5-FU infusion every 2 weeks) with bevacizumab (5mg/kg) followed by evaluating the liver resectability. (UMIN000001308) Results: Of the 40 pts enrolled from Sept. 9 2008 to Aug. 10 2010; M/F, 29/11; Median age, 63 years (range 37-74); ECOG PS 0/1, 38/2. The median number of administration cycles was 6 (range, 1–7). Response for CR, PR, SD, PD and NE were 0 (0 %), 12 (30.0 %), 22 (55.0%), 3 (7.5%) and 3 (7.5%), respectively. An overall response rate was 30.0% (95% CI: 16.6 % – 46.5 %). The grade 3-4 adverse events were; leukopenia (10%), neutropenia (32.5%), febrile neutropenia (5%), fatigue (2.5%), appetite loss (2.5%), diarrhea (2.5%), mucositis (2.5%), high AST (2.5%) and ileus (2.5%). The number of cases to intent operation was 17 (42.5%), the liver resectability was 16/40 (40.0 %). The number of R0 cases was 10 pts (25.0%, 95% CI; 12.7 - 41.2 %). Conclusions: mFOLFOX6 with bevacizumab regimen is safe and effective for unresectable liver limited metastases from colorectal cancer, and might be to lead the high liver resectability.

First-line carboplatin, pemetrexed, and panitumumab in patients with advanced nonsquamous KRAS wild type (WT) non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8062-8062 ◽  
Author(s):  
Tarek Mekhail ◽  
David Michael Waterhouse ◽  
Terence J. Hadley ◽  
Charles D. Webb ◽  
Howard A. Burris ◽  
...  
Keyword(s):  
Median Number ◽  
Phase Iii ◽  
First Line ◽  
Unresectable Stage ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
Unacceptable Toxicity ◽  
Severe Grade

8062 Background: KRAS WT colorectal cancer (CRC) is responsive to the EGFR inhibitors panitumumab (P) and cetuximab. Phase III data suggest a small, but statistically significant overall survival (OS) advantage with cetuximab + chemotherapy in KRAS unselected NSCLC (Pirker, Lancet 2009); and phase I data suggest P alone has activity in non-CRC tumors including NSCLC (Weiner, Clin Ca Res. 2008). This single-arm phase II trial examined the safety and efficacy of P in combination with carboplatin (C) and pemetrexed (Pem) in patients (pts) with advanced non-squamous KRAS WT NSCLC. The addition of P was hypothesized to improve the median time-to-progression (TTP) from 3.6 months (mos) (historical) to 5.4 mos (1-sided α .10, 80% power). Methods: Pts with previously untreated, unresectable stage IIIB/IV non squamous KRAS WT NSCLC received P 9 mg/kg, Pem 500 mg/m2, and C AUC=6 IV day 1 every 21 days for 6 cycles, followed by P and Pem maintenance every 21 days until progressive disease or unacceptable toxicity. Responses were evaluated every 2 cycles per RECIST 1.1. KRAS mutation testing was performed centrally (DxS kit). Tissue was also collected for EGFR FISH testing. Results: 60 pts were enrolled; median age, 65 years; 58% female, ECOG PS 0-1 (98%), and prior adjuvant chemotherapy (10%). Median number of cycles was 5 (range 1-22). At a median follow-up of 8.7 mos, the median TTP was 6.2 mos (95% CI: 3.7, 9.5), PFS 6.2 mos (95% CI 3.0, 9.0), 1 year OS 65.5% (95% CI 44.8%, 80%). 23 pts (38%) had partial responses (PR); the disease control rate (PR + proportion with stable disease) was 68%. Treatment-related toxicity (TRT) included (all grades) nausea (38%), fatigue (30%), rash (30%), and mucositis (23%). Severe (grade 3/4) TRT in > 2 pts included: thrombocytopenia (11%), neutropenia (7%), and dehydration (5%). There were no treatment-related deaths. EGFR mutation and FISH analyses will be presented. Conclusions: The addition of panitumumab to carboplatin and pemetrexed in the first-line treatment of advanced KRAS WT NSCLC was safe and well-tolerated; the median TTP of 6.2 mos met the primary endpoint. Definitive assessment of the value of panitumumab in this setting requires a randomized trial. Clinical trial information: NCT01042288.

scholarly journals PL2.2 Pembrolizumab (PEM) in recurrent high-grade glioma (HGG)patients with mismatch repair deficiency (dMMR): an observational study

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii2-iii2
Author(s):  
M Caccese ◽  
M Simonelli ◽  
M Fassan ◽  
M Padovan ◽  
P Persico ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitor ◽  
Brain Mri ◽  
High Grade Glioma ◽  
Median Number ◽  
Anaplastic Gliomas ◽  
Repair Deficiency ◽  
Grade 3 ◽  
Microsatellite Stability ◽  
Ecog Ps

Abstract BACKGROUND Pem, an immune checkpoint inhibitor, demonstrated to be activein various neoplasms with MMRd. No data exists about its efficacy in MMRdglioma patients. MATERIAL AND METHODS MMRd HGG relapsed after receiving RT and CT weretreated with Pem. MMR status was analyzed by immunohistochemistry,including the MLH1, MSH2, MSH6, and PMS2 markers. MMR deficiency wasdefined as presence of a weak (wMMRd) or absent (aMMRd) signal atimmunohistochemistry for at least one MMR protein. Other inclusion criteriawere: ECOG PS 0–2, histologically confirmed gliomas, dexamethasone ≤4 mg.Pem was administrated at 200 mg every 3 weeks until progression disease orunacceptable toxicity. Tumor response was evaluated by brain MRI every 10 weeksaccording to the RANO criteria. OS and PFS were evaluated by Kaplan-Meiercurves. CTCAE v4.0 was used for toxicity. RESULTS among 167 glioma patients, we found 22 MMRd gliomas. 12 PTS were treated with Pem: 8 wMMRd and 4 aMMRd. According to Bethesda criteria, allPTS had microsatellite stability. Tumor histologies included 5 anaplasticastrocytoma, 1 anaplastic oligodendroglioma, 6 glioblastoma (GBM). MSH2deficiency was found in 6 cases, MSH6 deficiency in 9 cases, PMS2 and MLH1deficiency in 2 cases. Median number of prior line of chemotherapy was 1 (range 1–5). Stable disease (SD) was reported in 4 PTS (33%); 8 PTS showedprogressive disease (PD). PTS with anaplastic gliomas showed a statisticallysignificant association with SD (p=0.03, OR=3); all GBM PTS reported PD; status of MMRd (weak/absent), IDH (mutated/wild-type), MSH2 and MLH6(deficient/proficient) were not associated with SD. Median follow up was 14.7 ms. OS was 5.6 ms (95% CI 0.1–13.8), PFS 2.4 ms (95% CI 1.8–2.9). OS was 2.8 ms and 5.6 ms (p=0.9), PFS was 1.8 ms and 3.1 ms (p=0.5) in PTS with wMMRd and aMMRd. PTS reporting SD and PD had PFS of 7.4 ms (95% CI 4.6–10.2) and 1.8 ms (95% CI 0.2–3.4), p=0.002; OS was “not reached” and 2.8 ms in PTS having SD vs PD (p=0.04). Grade ≥3 adverse eventswere reported in 8% of PTS. CONCLUSION a subgroup of recurrent MMRd HGG might benefit from Pem,especially anaplastic gliomas. There was a trend for a longer PFS and OS in PTS with aMMRd. Analyses for identifying additional molecular predictive factors is ongoing.

Docetaxel (T) followed by capecitabine (X) as first-line chemotherapy in patients (pts) with metastatic breast cancer (MBC): Preliminary findings from a phase II study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10692-10692
Author(s):  
J. L. Bayo ◽  
M. Lomas ◽  
J. Salvador ◽  
M. Ruiz ◽  
A. Moreno
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
First Line ◽  
Recent Trial ◽  
Highly Active ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Ecog Ps

10692 Background: X and 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-pretreated MBC [O’Shaughnessy et al. J Clin Oncol 2002]. The aim of this trial was to evaluate the efficacy and safety of sequentially administered T then X as first-line treatment in MBC. Methods: Pts ≥ 18 years with previously untreated, HER2neu-negative MBC, ECOG PS ≤ 2, were included in this prospective, multicenter, non-randomized, phase II study. Pts received 3 cycles of T (100mg/m2 d1) followed by 3 cycles of X (1250mg/m2 bid d1–14), every 3 weeks. Results: To date, 38 pts are evaluable for safety and 33 pts for efficacy. Baseline characteristics: median age 54.4 years (range 33–76); PS ≥ 1 50%; 36 (95%) pts had previous (neo)adjuvant anthracyclines, 8 (21%) concomitant with paclitaxel. The most frequent metastatic sites were: bone 47%, nodes 39% and liver 36%. 69% of pts had ≥ 2 metastatic sites. To date, 38 pts have received 3 cycles of T and 33 have also received 3 cycles of X. A total of 195 cycles have been administered: T 108 cycles (median 3, range 1–3); X 87 cycles (median 3, range 1–3). Dose reductions and interruptions for T vs. X were 32 vs. 21% and 21 vs. 21%, respectively. Median relative dose intensity: T 0.97 (range 0.62–1.00), X 0.93 (range 0.26–1.00). T grade 3/4 toxicities (37 evaluable pts): asthenia 19%, mucositis 16%, nausea 13%, febrile neutropenia 11%, rash 5%, diarrhea 5%, infection 3%. X grade 3/4 toxicities (33 evaluable pts): hand-foot syndrome 9%, diarrhea 9%, vomiting 9%, asthenia 6%, nausea 3%, anorexia 3%. In the 33 pts evaluable for efficacy, the RR was 61%, including 4 CRs and 16 PRs. At a median follow-up of 6.1 months, median TTP has not yet been reached. Conclusions: These preliminary results show that the sequential regimen of T followed by X is feasible, effective and well tolerated in first-line MBC, although giving X before T should also be investigated. Findings from a recent trial of XT vs. T followed by X [Beslija et al. ECCO 2005] suggest that XT should be standard in fit poor-prognosis pts with aggressive disease. No significant financial relationships to disclose.

FOLFOX-4 + cetuximab in untreated patients with advanced colorectal cancer. A phase II study of the Gruppo Oncologico dell’Italia Meridionale (prot. GOIM 2402)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3559-3559 ◽  
Author(s):  
G. Colucci ◽  
F. Giuliani ◽  
R. Mattioli ◽  
C. Garufi ◽  
R. Mallamaci ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Disease Status ◽  
First Line ◽  
Preliminary Results ◽  
Grade 3 ◽  
Line Setting ◽  
Ecog Ps

3559 Background: Cetuximab is an IgG monoclonal antibody targeting the EGFR showing to be effective both as single agent or in combination with Irinotecan (CPT-11) or Irinotecan/FU/FA in patients (pts) with EGFR-expressing metastatic colorectal cancer (CRC) in the first and second/subsequent-line setting. The current trial was designed to evaluate the efficacy and the safety of Cetuximab plus Folfox-4 as first -line treatment. The main objective was the percentage of confirmed objective response rate. Methods: Chemonaivepts with non-resectable metastatic CRC and expressing EGFR were treated with Cetuximab (400 mg/m2 week 1 and 250 mg/m2 weekly thereafter) plus Folfox-4 (every 2 weeks: Oxaliplatin 85 mg/m2, day 1; FA 100 mg/m2 2h, simultaneously with OH-P, and FU 400 mg/m2 iv bolus followed by 600 mg/m2 iv for 22h on days 1 and 2). The first evaluation of disease status (Recist criteria) was performed after the first 4 cycles and confirmed after one month. The treatment was continued until a maximum of 12 cycles of chemotherapy; the maintenaice with Cetuximab was permitted. Preliminary results: On the 65 screened pts, 47 (72%) had EGFR-expressing metastatic disease and were enrolled. Their main characteristics were: median Ecog PS 0; median age 66 yrs (range 43–74); main sites of disease: liver 31, lung 12, lymph-nodes 3, others 8. To date twenty-two pts are evaluable for activity and 27 for toxicity; 2 pts are not evaluable and 25 are too early. We observed 16 PR (72.7%), 5 NC (22.7%) and 1 PD (4.6%) for an ORR of 72.7% and a TGCR of 95.4%; the confirmed PR were 15 (68%). To date 2 pts undergone surgery of their metastases both for lung. The main adverse events grade 3/4 (NCI criteria) were: acne-like rush 18.5%, diarrea 7%, nausea/vomiting 4% and anemia 4%. Conclusions: Our preliminary results confirm that the combination of Cetuximab plus Folfox-4 has an high activity and a good safety profile in advanced CRC pts. The study is ongoing. No significant financial relationships to disclose.

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.

Randomized multicenter phase III trial of oxaliplatin plus raltitrexed compared to oxaliplatin plus fluorouracil and leucovorin treatment in recurrent and metastatic colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4102-4102
Author(s):  
J. Wang ◽  
J. Li ◽  
S. Qin ◽  
T. Liu ◽  
Z. Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Median Number ◽  
Disease Control Rate ◽  
Phase Iii ◽  
Progression Of Disease ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps

4102 Purpose: To compare oxaliplatin (L-OHP) plus raltitrexed (RTX) with L-OHP plus fluorouracil and leucovorin (LV/5FU) for patients (pts) with recurrent and metastatic colorectal cancer(CRC). Methods: Eligible pts had to have histologically proven recurrent or metastatic CRC,not having previously received oxaliplatin as palliative chemotherapy,ECOG PS = 2,age:18∼70,and adequate hematological,renal and hepatic function.After written informed consent,pts were randomized to L-OHP:130 mg/m2 d1 + RTX: 3 mg/m2 d1 (Arm A) or + LV: 200 mg/m2 + 5FU:375 mg/m2 d1–5 (Arm B). Results: Between Jan 2005 and July 2006, 216 pts were enrolled at 15 centers in China.112 pts (mean age: 55.0 (19∼70), M/F: 57/46, PS 0/1/2: 46/53/13) were randomly assigned to A and 102 (mean age: 54.2(22∼70), M/F: 54/46, PS 0/1/2: 44/59/9) to B. 203 pts were eligible for response evaluation (A:103, B:100).The median number of cycles was 4 (1∼6) in A and 3 (1∼6) in B (P=0.1431).The RR was 29.1% (CR:2, PR:28, SD:50 , PD:23) in A and 17.0% (CR:2, PR:15, SD:46 , PD:37) in B (P=0.0437).The disease-control rate was 77.7% in A and 63.0% in B (P=0.0237). After a median follow-up of 10 months (4–16.5),92 pts had had progression of disease (40 in A and 52 in B); 73 deaths had occurred (35 in A and 38 in B), median time to progression was not reached. Following-up is ongoing.The median QoL scores for the two arms were comparable. 214 were included in the safety analyses (A:112, B:102). There was a higher incidence of neutropenia (48.2% verse 29.4%, P=0.005) and transaminase increase (49.1% verse 35.3%, P=0.041) among A. Grade 3 or 4 neutropenia was much common in pts in A than those in B (20.5% verse 4.9% , P=0.001), but was complicated by fever in only 3.6% of cases (4 pts) in A and in 2.9% of cases (3 pts) in B. No pts were dead or infectious due to neutropenia. There were similar rates of grade 3 or 4 transaminase elevation in the two groups. Vomitting and anorexia were much commoner with B. Conclusions: The L-OHP+RTX seems beneficial in recurrent and metastatic CRC, demonstrating better response rate and higher disease control rate with acceptable tolerability, maintenance of QoL and convenient administration schedule. 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.

A randomized phase II study of perifosine (P) plus imatinib for patients with imatinib-resistant gastrointestinal stromal tumor (GIST)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10563-10563 ◽  
Author(s):  
A. P. Conley ◽  
D. Araujo ◽  
J. Ludwig ◽  
V. Ravi ◽  
B. L. Samuels ◽  
...  
Keyword(s):  
Phase Ii ◽  
Median Number ◽  
Blurred Vision ◽  
Imatinib Resistance ◽  
Choi Criteria ◽  
Grade 3 ◽  
Exon 11 ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
Advanced Gist

10563 Background: P inhibits activation of the Akt pathway which results in apoptosis and block cancer cell proliferation. Since AKT is a molecule downstream of Kit, its inhibition may overcome Kit-dependent imatinib resistance. We performed a phase II trial to assess antitumor activity of perifosine in patients with advanced GIST who were refractory to imatinib mesylate. Methods: Pts with Kit(+) advanced GIST who have PD on IM were eligible. Pts continued their current dose of IM and were randomized to one of two dosing schedules of P (Arm A: 100 mg p.o. qd x 28 + IM or Arm B: 900 mg [300 mg p.o tid] qweekly + qd IM). A Bayesian approach was utilized to assess a target response rate or 20% with an unacceptable toxicity rate of 15% or less. Response was measured at q8 wk intervals by RECIST and Choi criteria. The primary endpoint was to determine the efficacy of P with IM in pts with advanced GIST with PD while receiving IM. Results: From 8/2005 to 7/2008, 41 pts were accrued. After 1 pt exclusion and 2 cross-overs, 22 pts were in Arm A and 18 pts in Arm B. Median age was 58 (range, 32–82), 51% were male, and median ECOG PS was 1. The most common primary site of disease and metastasis was the stomach (29%) and liver (66%), respectively. KIT genotype was available for 22 pts(54%); 5(12%) WT, 13(32%) exon 11 mutations, and 4(10%) exon 9 mutations. The median number of cycles was 2 (range, 1–24). By Choi and RECIST, 30 pts(73%) and 36 pts(87%) were available for response, respectively. No CR was identified but the PR rate was 4/36 (11%) by Choi (4 PR, 9 SD) and 0/36 (0%) by RECIST (16 SD). 4/5 (80%) of pts with WT KIT appeared to benefit (Choi: 1 PR, 3 SD; RECIST: 4 SD). Median PFS and OS for 40 pts were 2.2 months and 18.3 months. No difference in PFS was noted for the 2 schedules. Toxicity was assessed in 39 pts; 46 grade 3 events and 4 grade 4 events (ALT elevation, blurred vision, fatigue, and mood alteration) were noted. The most common grade 3 event was fatigue (20%). Three pts (7%) were removed from the study for toxicity (Arm A:1 pt, Arm B:2 pts). Conclusions: The addition of P to IM has minimal activity in IM-refractory GIST although its activity in GIST with WT KIT may be further investigated. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document