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.

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]

Liver resectability following S-1+L-OHP with cetuximab as the first-line treatment of unresectable liver limited metastases from KRAS exon 2 wild-colorectal cancer in Japanese patients (KSCC 1002).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 755-755
Author(s):  
Yuji Miyamoto ◽  
Yasunori Emi ◽  
Shoji Tokunaga ◽  
Toru Beppu ◽  
Yoshihiro Kakeji ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Resection ◽  
Line Treatment ◽  
Phase Ii Trials ◽  
First Line ◽  
Eligibility Criteria ◽  
Exon 2 ◽  
Ecog Ps ◽  
Kras Exon ◽  
First Line Treatment

755 Background: There is no data concerning liver resectability following S-1+L-OHP (C-SOX) with cetuximab (Cmab) as the first-line treatment of unresectable liver limited metastases from KRAS exon 2 wild-colorectal cancer by prospective, multi-center study in Japan. The Kyushu Study group of Clinical Cancer (KSCC) conducted phase II trials 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 4-6 cycles of C-SOX (oxaliplatin 130 mg/m2, day 1 followed by S-1 80 mg/m2 po [days 1-14] every 3 weeks) with weekly durable intravenous (DIV) Cmab administration at 400 mg/m2 (day 1) and 250 mg/m2/week (except day 1), followed by evaluating the liver resectability. Results: Of the 33 pts enrolled from March 2010 to July 2013; M/F, 20/13; median age, 64 years (range 48-83); ECOG PS 0/1, 27/6; primary lesion -/+, 18/15; number of liver metastasis 1-4/5 or more, 10/23; uni-/bi-lobular liver meta. 5/28; synchronous/metachronous 30/3. The number of FAS and SAS cases was 33. Response without confirmation for CR, PR, SD, PD and NE were 1 (3.0%), 20 (60.6%), 6 (18.2%), 3 (9.1%) and 3 (9.1%), respectively. An overall response rate was 63.6% (95% CI: 46.3–81.0%). The liver resectability for all time treatment was 16/33 (48.5%). The number of R0 cases was 13 pts (39.4%). Median progression free survival (liver resection was not censored and not event, events = relapse, progression, secondary cancer, and death) for 16 liver resection cases and 17 not-resection cases were 25.0 months (8.1-not reached), 4.5 months (3.0-10.8), respectively. Median overall survival (mOS) for all 33cases was 31.6 months (14.8, not reached). Median OS for 17 not-resection cases was 14.0 (6.4-not reached), and mOS for 16 liver resection cases was not reached and 3-year survival rate was 51.4%. Conclusions: C-SOX + Cmab regimen is safe and effective for unresectable liver limited metastases from KRAS exon 2 wild-colorectal cancer, and might be to lead the high liver resectability. Clinical trial information: UMIN000004331.

Phase III Multicenter Randomized Trial of Oxaliplatin Added to Chronomodulated Fluorouracil–Leucovorin as First-Line Treatment of Metastatic Colorectal Cancer

2000 ◽  
Vol 18 (1) ◽  
pp. 136-136 ◽  
Author(s):  
S. Giacchetti ◽  
B. Perpoint ◽  
R. Zidani ◽  
N. Le Bail ◽  
R. Faggiuolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Phase Iii ◽  
Line Treatment ◽  
Survival Times ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)–leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m2/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m2, as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU–LV occurred in ≤ 5% of the patients (≤ 1% of the courses). Grade 3 to 4 diarrhea occurred in 43% of the patients given l-OHP (10% of the courses), and less than 2% of the patients had severe hematotoxicity. Thirteen percent of the patients had moderate functional impairment from peripheral sensory neuropathy. Sixteen percent of the patients receiving 5-FU–LV had an objective response (95% confidence interval [CI], 9% to 24%), compared with 53% of those receiving additional l-OHP (95% CI, 42% to 63%) (P < .001). The median progression-free survival time was 6.1 months with 5-FU–LV (range, 4.1 to 7.4 months) and 8.7 months (7.4 to 9.2 months) with l-OHP and 5-FU–LV (P = .048). Median survival times were 19.9 and 19.4 months, respectively. CONCLUSION: By chronomodulating 5-FU–LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.

scholarly journals Comparison between the three oxaliplatin-based regimens with bevacizumab in patients with metastatic colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 687-687
Author(s):  
Yoshihito Ohhara ◽  
Mitsukuni Suenaga ◽  
Satoshi Matsusaka ◽  
Eiji Shinozaki ◽  
Nobuyuki Mizunuma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Kaplan Meier ◽  
Hand Foot Syndrome ◽  
Chemotherapeutic Treatment ◽  
Grade 3 ◽  
First Line Treatment

687 Background: XELOX (capecitabine/L-OHP) therapy that includes orally administered fluoropyrimidine instead of infusional fluorouracil (5-FU) was approved for metastatic colorectal cancer (mCRC) in Sep 2009 in Japan. A pivotal trial (NO16966 study) demonstrated the non-inferiority of XELOX to FOLFOX (5-FU/L-OHP/LV) and the superiority of those L-OHP-based regimens plus bevacizumab (BV) to those without in the first-line treatment of mCRC. We evaluated the safety and efficacy of XELO+BV compared with FOLFOX4 or mFOLFOX6 plus BV in the first-line treatment for mCRC patients at a single institute. Methods: Between Jun 2007 and Nov 2008, 85 patients received FOLFOX4+BV (FF4 arm), between Dec 2008 and Sep 2009, 40 patients received mFOLFOX6+BV (FF6 arm), and between Oct 2009 and Sep 2010, 60 patients received XELOX+BV (XELOX arm). The best overall responses were evaluated using RECIST 1.0 during chemotherapeutic treatment, and adverse events were graded according to CTCAE ver.3.0. Progression-free survival (PFS) was estimated by Kaplan-Meier methods. Results: Characteristics of patients of FF4 arm, FF6 arm, and XELOX arm were below: median age, 60 yr vs. 62 yr vs. 60.5 yr; gender (male), 48.2 % vs. 62.5 % vs. 58.3%. The overall response rates (CR+PR) were 61.1 %, 72.5 %, and 75 % (95% CI; 50.6-71.8%, 58.0-87.0%, and 63.7-86.3%). Median PFS were 17.0 months, 15.5 months, and 14.4 months, respectively (cut-off: Aug 31, 2011). There were no statistical significances not only between FF4 arm and FF6 arm (log-rank; p=0.641), but also between XELOX arm and FF4+FF6 (FOLFOX) arm (log-rank; p=0.138). FOLFOX arm was associated with higher incidence of grade 3/4 neutropenia than XELOX arm. Grade3 diarrhea and hand-foot syndrome (HFS) were more frequent in XELOX arm. Conclusions: This study suggests that XELOX arm was equal to FOLFOX arm, regardless of regimen, in tumor response and PFS. Further follow-up is necessary to confirm the benefit on survival.

Phase II trial of radiation therapy/temozolomide followed by temozolomide/sorafenib in the first-line treatment of glioblastoma multiforme (GBM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2018-2018
Author(s):  
R. E. Lamar ◽  
D. R. Spigel ◽  
H. A. Burris ◽  
T. M. Markus ◽  
M. Kuzur ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Line Treatment ◽  
First Line ◽  
Complete Surgical Resection ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
X 24 ◽  
Ecog Ps ◽  
First Line Treatment

2018 Background: Anti-angiogenesis agents have recently shown activity in the treatment of patients (pts) with GBM. We added sorafenib, a multi-targeted TKI, to the standard first-line treatment of patients with GBM. Methods: Pts with histologically documented GBM were eligible at diagnosis or after resection. Additional entry criteria: ECOG PS 0 or 1; adequate organ function; ability to swallow pills; standard exclusions for antiangiogenesis agents. All pts initially received radiation therapy (total 60 Gy, 2 Gy by single daily fractions) plus temozolomide (75mg/m2 po daily). Four weeks after completion of radiation therapy, pts received temozolomide (150mg/m2 po days 1–5, repeated every 21 days for 6 cycles) plus sorafenib (400mg po bid daily x 24 weeks). Pts were evaluated every 8 weeks during temozolomide/sorafenib therapy, and every 3 months after therapy ended, until tumor progression. Median PFS was the primary endpoint. Results: Between April 2007 and July 2008, 45 pts were enrolled. The median age was 54 years; 30 pts (67%) had previous partial or complete surgical resection. 39 pts (87%) completed concurrent RT/temozolomide therapy, while 6 pts were removed from treatment (PD 4, toxicity 1, intercurrent event 1). 39 pts began treatment with temozolomide/sorafenib; 3 have completed all planned treatment, 8 remain on treatment, and 28 stopped treatment early (PD 22, toxicity 2, intercurrent event 1, pt decision 3). Best responses are as follows: CR, 1 pt (2%); PR, 5 pts (11%); stable disease, 22 pts (49%); progressive disease, 14 pts (31%). After a median follow-up of 9 months, median PFS for all pts was 6 months (95% confidence intervals, 2.7–7.8 months). Median PFS for pts who received at least 1 dose of sorafenib is also 6 months. The median overall survival is 16 months (95% CI, 7.2-NR months). Grade 3/4 toxicity during temozolomide/sorafenib was uncommon; 7 pts (16%) required dose reductions of sorafenib during their treatment course. Conclusions: The addition of sorafenib to standard treatment with RT/temozolomide is feasible and well tolerated by most pts. Preliminary efficacy is similar to standard therapy; updated results will be presented. [Table: see text]

FOLFIRI + bevacizumab as first-line treatment in advanced colorectal cancer (ACC): Final results (prot. GOIM 2601)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15007-e15007
Author(s):  
F. Giuliani ◽  
F. De Vita ◽  
V. Lorusso ◽  
S. Cinieri ◽  
I. Nugnes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Data ◽  
Advanced Colorectal Cancer ◽  
Median Number ◽  
Line Treatment ◽  
First Line ◽  
Bleeding Events ◽  
History Of ◽  
Optimal Regimen ◽  
First Line Treatment

e15007 Background: The addition of Bev to IFL obtained better OS and RR than chemotherapy alone. However IFL is not considered an optimal regimen and is certainly more toxic than FOLFIRI. To investigate the activity and efficacy of the addition of Bev to FOLFIRI, the GOIM started the following phase II study. Methods: seventy-two untreated pts with histologically/citologically confirmed diagnosis of colorectal cancer, with at least one measurable disease, age > 18 yrs, PS < 2 (ECOG), adequate bone marrow reserve and hepatic and renal function, with no history of cardiovascular disease, thromboembolic events or coagulative disorders and who signed informed written consent, were enrolled and received the following treatment: CPT-11 at 180 mg/m/mq on day 1, FA at 100 mg/mq as 2h infusion on days 1–2, FU at 400 mg/mq bolus on days 1–2 and FU at 600 mg/mq as 22h infusion on days 1–2 (FOLFIRI) plus Bev at 5 mg/Kg on day 1, every two weeks. A maximum of 12 cycles of chemotherapy was planned and a maintenance with Bev for 6 months was permitted. The evaluation of activity (Recist criteria) was performed every 4 cycles Results: all the enrolled pts were evaluable for activity and safety. Their main characteristics were M/F: 38/34; median PS: 0; median age 60 (range 33–73); primary site colon/rectum: 50/22 (69.4%/30.6%); main sites of disease liver: 50 (69.4%), lung: 18 (25%), lymph nodes: 19 (26.4%); synchronous/metacronous disease: 55/17 (77.7%/22.3%); multiple/single lesions: 40/32 (55.5%/44.5%).Seven (9.6%) CR, 25 (34.8%) PR, 33 (45.8%) SD and 7 PRO were observed for an ORR of 44.4% and a disease control of 90.3%. The response rate according to the main sites of disease were: liver 25/50 (50%), lung 6/18 (33.3%). The median number of administered cycle were 9 and the median TTP was 10.0 months. The main haematologic side-effects (% G3–4 NCI criteria) were: neutropenia 11%, thrombocytopenia 2.7% and anemia 4.7%, while diarrhea affected only 2.7% of pts; hypertension, thromboembolic and bleeding events were observed in 2.7%, 1.3% and 1.3% respectively. Conclusions: the addition of Bev to FOLFIRI is an active and effective first-line treatment in ACC with a good safety profile. Survival data will be presented during the meeting. No significant financial relationships to disclose.

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