Phase II Study of Capecitabine, Oxaliplatin, and Erlotinib in Previously Treated Patients With Metastastic Colorectal Cancer

2006 ◽  
Vol 24 (12) ◽  
pp. 1892-1897 ◽  
Author(s):  
Jeffrey A. Meyerhardt ◽  
Andrew X. Zhu ◽  
Peter C. Enzinger ◽  
David P. Ryan ◽  
Jeffrey W. Clark ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Early Stage ◽  
Progression Free Survival ◽  
Early Stage Disease ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3

Purpose To investigate the combination of erlotinib, capecitabine, and oxaliplatin in patients who were previously treated for metastatic colorectal cancer. Patients and Methods Patients were eligible if they had metastatic colorectal cancer that progressed, were intolerant to first-line chemotherapy, or had disease recurrence within 1 year of adjuvant therapy for early-stage disease. Each 21-day cycle consisted of daily oral erlotinib at 150 mg, oral capecitabine at 1,000 mg/m2 (reduced to 750 mg/m2 after the first 13 patients) twice a day on days 1 to 14, and intravenous oxaliplatin at 130 mg/m2 on day 1. Results Thirty-two patients were enrolled onto this phase II study. By intention-to-treat analyses, eight patients (25%) experienced a partial response and 14 patients (44%) had stable disease for at least 12 weeks. The median progression-free survival was 5.4 months and the median overall survival was 14.7 months. These results were essentially unchanged when limited to the cohort of patients (78%) who received prior irinotecan for metastatic colorectal cancer. Most common grade 3 to 4 toxicities included diarrhea (38%), nausea/emesis (19%), fatigue (16%), dehydration (16%), and dermatitis (13%); grade 3 or 4 toxicities were reduced with a lower starting dose of capecitabine. Conclusion The combination of capecitabine, oxaliplatin, and erlotinib seems to have promising activity against metastatic colorectal cancer in patients who received prior chemotherapy, with a relatively higher response rate and progression-free survival compared with previous reports of either infusional FU, leucovorin, and oxaliplatin or capecitabine and oxaliplatin in similar patient populations.

A phase II study of irinotecan combined with S-1 in patients with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy

2019 ◽  
Vol 29 (3) ◽  
pp. 474-479
Author(s):  
Seiji Mabuchi ◽  
Eriko Yokoi ◽  
Kotaro Shimura ◽  
Naoko Komura ◽  
Yuri Matsumoto ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Cervical Cancer ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Previously Treated ◽  
Grade 3

ObjectivesWe conducted a phase II study to investigate the efficacy and toxicities of irinotecan plus oral S-1 in patients with advanced or recurrent uterine cervical cancer.MethodsPatients with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy were enrolled. Irinotecan (150 mg/m2) was administered intravenously over the course of 90 min on day 1, and S-1 (80 mg/m2) was given orally in two divided doses from days 1 to 14 of a 21 day cycle. The primary endpoint of this phase II study was response rate. Secondary endpoints included safety, progression free survival, and overall survival.ResultsA total of 19 patients were enrolled and treated. The response rate was 29.4%. Grade 3–4 hematologic toxicities were observed in three patients (15.7%). The only grade 3–4 non-hematologic toxicity observed was grade 3 diarrhea. The median progression free survival and overall survival were 3 months and 9 months, respectively.ConclusionS-1 plus irinotecan in a 3 weekly setting is safe and active in women with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy. Future corroborative clinical studies are warranted.

RECIST and iRECIST criteria for the evaluation of nivolumab + ipilimumab combination in patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC): Results of the GERCOR NIPICOL phase II study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 101-101 ◽  
Author(s):  
Romain Cohen ◽  
Jaafar Bennouna ◽  
Julie Henriques ◽  
Christophe Tournigand ◽  
Christelle De La Fouchardiere ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Low Frequency ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3 ◽  
Clinical Trial Information

101 Background: Immune checkpoint inhibitors (ICKi) are highly effective for MSI/dMMR mCRC pts. RECIST1.1 criteria are reported to underestimate response to ICKi. The GERCOR NIPICOL phase II study aimed to evaluate disease control rate (DCR) using RECIST1.1 and iRECIST for MSI/dMMR mCRC pts treated with nivolumab (NIVO) and ipilimumab (IPI). Methods: MSI/dMMR mCRC pts previously treated with fluoropyrimidines (FP), oxaliplatin (OX) and irinotecan (IRI) ± targeted therapies received NIVO 3 mg/kg + IPI 1 mg/kg Q3W for 4 cycles then NIVO 3 mg/kg Q2W until progression or a maximum of 20 cycles. CT-scan tumor assessments were done every 6 weeks during 24 weeks and then every 12 weeks. Primary objective was DCR at 12 weeks (12wDCR) according to RECIST1.1 and iRECIST by central review. Response rates and progression-free survival (PFS) by central review were secondary objectives. A one-stage Fleming design was used with a targeted improvement of 12wDCR from 70% to 85%. Results: Of 57 pts included between Dec 2017 and Nov 2018, 43.9% had received ≥ 3 prior lines including FP (100%), OX (100%), IRI (95.5%), antiangiogenics (57.9%) and anti-EGFRs (45.6%). 17.5% of pts had BRAF mutation and 27.5% Lynch syndrome. Grade 3-4 treatment-related adverse events were reported in 49.1% of pts, mainly hepatitis (12.3%). 12wDCR was 86.0% and 87.7% using RECIST1.1 and iRECIST respectively, with only 1 pseudo-progression (1.8%) observed during the first 12 weeks, and one later. Kappa coefficient between RECIST and iRECIST 12wDCR was 0.92 (95%CI 0.77-1.0). Best observed responses with RECIST1.1/iRECIST were: 2/2 complete responses (3.5/3.5%), 19/19 partial responses (33.3/33.3%), 30/31 stable diseases (52.6/54.4%) and 3/2 disease progressions (5.3/3.5%), with 3 pts not evaluable (cancer-related deaths before first evaluation). Conclusions: Combination of NIVO and IPI in MSI/dMMR mCRC is associated with a low frequency of pseudo-progression and high DCR rate. PFS will be evaluated in Dec 2019, with all pts having completed the predefined 1-year of ICKi therapy. Clinical trial information: NCT033501260.

scholarly journals Multicenter Phase II Study of a New Effective S-1 and Irinotecan Combination Schedule in Patients with Unresectable Metastatic or Recurrent Colorectal Cancer

2013 ◽  
Vol 7 ◽  
pp. CMO.S10769 ◽  
Author(s):  
◽  
Yutaka Ogata ◽  
Takaho Tanaka ◽  
Yoshito Akagi ◽  
Nobuya Ishibashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Median Overall Survival ◽  
Overall Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Colorectal Cancer ◽  
Free Survival ◽  
Multicenter Phase ◽  
Grade 3

Introduction This multicenter phase II study determined the efficacy and safety of new daily oral S-1 and weekly irinotecan (CPT-11) combination schedule in patients with previously untreated advanced or recurrent colorectal cancer. Patients and Methods Patients received first-line chemotherapy comprising S-1 80 mg/m2/day given on days 3 to 7, 10 to 14, and 17 to 21 and 60 mg/m2 CPT-11 administered intravenously on days 1, 8, and 15 of a 28-day cycle. Results A total of 45 eligible patients were enrolled in this study. The overall response rate was 48.9%. Median progression-free survival and median overall survival was 8.1 months and 20.9 months, respectively. The rates of grade 3 or 4 toxicity were as follows: neutropenia, 8.9%; anemia, 4.4%; anorexia, 6.7%; and diarrhea, 6.7%. Conclusions This new S-1 and irinotecan combination schedule appeared to be an effective, well-tolerated, and convenient regimen in patients with advanced colorectal cancer as compared with conventional regimens such as FOLFIRI and IRIS.

Phase II study of S-1 plus leucovorin (a new 1-week treatment regimen followed by a 1-week rest period) in patients with untreated metastatic colorectal cancer in Japan and China.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 598-598 ◽  
Author(s):  
Tadamichi Denda ◽  
Jin Li ◽  
Ruihua Xu ◽  
Jianming Xu ◽  
Koji Ikejiri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Treatment Regimen ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Study ◽  
Rest Period ◽  
Progression Free Survival ◽  
Grade 3 ◽  
Japan And China

598 Background: The previous phase II study of the oral S-1 plus oral Leucovorin (LV) (2 weeks’ treatment regimen followed by a 2 week rest period) for patients (pts) with untreated metastatic colorectal cancer (mCRC) have shown to be effective, but the grade 3 toxicities (diarrhea, stomatitis, and anorexia) were observed with relatively high frequency. In this phase II study, we tried to improve the administration schedule of S-1 plus LV regimens for well-tolerated toxicities and evaluated the efficacy. Methods: Pts were eligible as follows: histologically confirmed adenocarcinoma, age≥20, ECOG PS 0-1, no prior chemotherapy, at least one measurable lesion by RECIST ver1.0 criteria, adequate organ function, and written informed consent. S-1 (40-60 mg bid) and LV (25 mg bid) were orally administered for 1 week, followed by an 1 week rest period. Treatment was repeated until the onset of disease progression or unacceptable adverse events occurred. The primary endpoint was the response rate (RR), and the secondary endpoints were efficacy and safety. Results: From October 2008 to June 2009, 73 pts were enrolled in Japan and China. Of the eligible 71 pts, median age was 60 (range 27-84), Male/Female was 38/33, PS:0/1 was 39/32, and Japan/China was 32/39. RR as primary endpoint was 53.5% (95% CI, 41.3-65.5), and Disease Control Rate was 83.1%. With a median follow-up period of 26.4 months, the median Progression Free Survival was 6.5 months. Median Overall Survival was 24.3 months with the survival rate of 77.5 % at 1 year and 53.2 % at 2 years. The incidences of grade 3 adverse drug reactions were diarrhea 8.3 %, stomatitis 8.3%, anorexia 2.8%, neutropenia 9.7%, and there was no treatment-related death. Conclusions: The newly improved 1 week S-1 plus LV treatment regimen showed good efficacy and better tolerability than the 2 weeks’ treatment regimen. This therapy showed promising activity in pts with untreated mCRC without the concurrent use of irinotecan, oxaliplatin, or molecular-targeted drugs. This trial was supported by Taiho Pharmaceutical CO., LTD. ClinicalTrials.gov Identifier: NCT00891332 .

FOLFIRI3-aflibercept as second- or later-line therapy in patients with metastatic colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 817-817 ◽  
Author(s):  
Candice Carola ◽  
Francois Ghiringhelli ◽  
Stefano Kim ◽  
Thierry Andre ◽  
Juliette Barlet ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Free Survival ◽  
Line Therapy ◽  
Prior Use ◽  
Secondary Endpoints ◽  
Previously Treated ◽  
Minimal Modification ◽  
Grade 3

817 Background: The efficacy of the standard FOLFIRI-aflibercept second-line therapy may be improved by the chemotherapy regimen in metastatic colorectal cancer (MCRC). FOLFIRI was optimized by splitting the dose of irinotecan on day 1 and day 3 and by removing the bolus of 5-FU in the FOLFIRI3 regimen. Methods: This is a retrospective multicentric cohort, evaluating efficacy and safety of the association of aflibercept with FOLFIRI3, in patients (pts) with previously treated MCRC. The primary endpoint was overall response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: From September 2014 to December 2016, 74 pts were treated in four French centers. Nine pts were excluded due to prior use of aflibercept (n = 3), more than one prior line of treatment in irinotecan-naïve pts (n = 3) and inadequate liver function (n = 3). In the cohort of irinotecan-naïve pts (n = 30), ORR and DCR were 43.3% and 76.7%. Median PFS and OS were 11.3 months (95% CI 6.1-29.0) and 17.0 months (95% CI 13.0-17.3). The most common ( > 5%) grade 3-4 adverse events were diarrhea (37.9%), neutropenia (14.3%), stomatitis and anemia (10.4%), hypertension (6.7%). In the cohort of pts previously treated with irinotecan (n = 35), 20 (57.1%) pts received ≥2 prior lines of treatment with various prior irinotecan regimen (FOLFIRINOX, n = 21; FOLFIRI, n = 10; FOLFIRI3, n = 4). ORR and DCR were 34.3% and 60.0%. Median PFS and OS were 5.7 months (95% CI 3.9-10.4) and 14.3 months (95% CI 12.8-19.5). In 4 patients refractory to irinotecan, FOLFIRI3-aflibercept led to one partial response, 2 stabilizations, and one patient not evaluable. Conclusions: A minimal modification of the FOLFIRI regimen led to a dramatically improvement of efficacy with FOLFIRI3-aflibercept, whatever prior use of irinotecan. Further randomized trial is planned.

Multicenter Phase II Study of Bimonthly High-Dose Leucovorin, Fluorouracil Infusion, and Oxaliplatin for Metastatic Colorectal Cancer Resistant to the Same Leucovorin and Fluorouracil Regimen

1999 ◽  
Vol 17 (11) ◽  
pp. 3560-3568 ◽  
Author(s):  
Thierry André ◽  
Mohamed A. Bensmaine ◽  
Christophe Louvet ◽  
Eric François ◽  
Virginie Lucas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peripheral Neuropathy ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
High Dose ◽  
Median Response ◽  
Grade 3

PURPOSE: To evaluate the objective tumor response rates and toxicities of leucovorin (LV) plus fluorouracil (5-FU) cancer regimen combined with oxaliplatin (85 mg/m2) every 2 weeks on metastatic colorectal cancer patients with documented proof of progression while on bimonthly LV and 5-FU alone. PATIENTS AND METHODS: One hundred patients were enrolled onto this study and 97 received the study drugs between October 1995 and December 1996. Eighty-nine patients were eligible for per-protocol efficacy analysis with documented proof of progression on one of the following two treatments: LV 500 mg/m2 and continuous 5-FU infusion 1.5 to 2 g/m2/22 hours, days 1 through 2 every 2 weeks (FOLFUHD); or LV 200 mg/m2, bolus 5-FU 400 mg/m2, and continuous 5-FU infusion 600 mg/m2/22 hours, days 1 through 2 every 2 weeks (LV5FU2). In our study, 40 patients received FOLFUHD + 85 mg/m2 of oxaliplatin day 1 (FOLFOX3) and 57 patients received LV5FU2 + 85 mg/m2 of oxaliplatin day 1 (FOLFOX4). RESULTS: Of the 97 patients treated, 20 partial responses were observed (FOLFOX3/4: response rate, 20.6%; 95% confidence interval, 13% to 31.1%; FOLFOX3: response rate,18.4%; FOLFOX4: response rate, 23.5%). For patients treated with FOLFOX3/4, the median response duration for was 7.5 months, and the major toxicities were peripheral neuropathy and neutropenia. The incidence of grade 3 (National Cancer Institute common toxicity criteria) peripheral neuropathy was 20.6%; whereas the overall incidence of grade 3 to 4 neutropenia was 27.8%, 15%, and 36.9% for FOLFOX3/4, FOLFOX3, and FOLFOX4, respectively (P = .02). From the start of treatment, median progression-free survival was 4.7, 4.6, and 5.1 months for FOLFOX3/4, FOLFOX3, FOLFOX4, respectively, and median overall survival was 10.8, 10.6, and 11.1 months, respectively. CONCLUSION: This phase II study of oxaliplatin at 85 mg/m2 in combination with bimonthly LV plus 5-FU in patients with colorectal cancer resistant to LV plus 5-FU alone confirms the enhanced antitumor activity of oxaliplatin in combination with 5-FU.

Panitumumab or cetuximab combined with irinotecan in patients with KRAS wild-type metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 642-642
Author(s):  
Nobuaki Ikezawa ◽  
Satoru Iwasa ◽  
Hirokazu Shoji ◽  
Yoshitaka Honma ◽  
Atsuo Takashima ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Group Versus ◽  
Progression Free Survival ◽  
Similar Response ◽  
Wild Type ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3

642 Background: Panitumumab and cetuximab are known to be effective in KRAS wild-type metastatic colorectal cancer (mCRC). However, it is not clear whether panitumumab and irinotecan confers benefit that are comparable to those of cetuximab and irinotecan in patients with KRAS wild-type mCRC previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimes. Methods: We analyzed 139 patients who had received panitumumab or cetuximabu combined with irinotecan for KRAS wild-type mCRC previously treated with fluor opyrimidine-, oxaliplatin-, and irinotecan-based regimes.We evaluated and compared efficacy and safety of panitumumab plus irinotecan and cetuximab plus irinotecan. Results: Baseline characteristics were similar for the two groups receving cetuximab pulus irinotecan (n = 97) and panitumumab plus irinotecan (n = 42),respectively.In patients with measurable lesions,the response rate (unconfirmed complete or partial response) were 20% (18/92) in the group receving cetuximab plus irintecan and 34% (14/41) in that receving panitumumab plus irinotecan. Median progression-free survival was 5.7 months in the cetuximab plus irinotecan group versus 4.3 months in the panitumumab plus irinotecan group. Median overall survival was 11.2 months in the cetuximab plus irinotecan group versus 13.6 months in the panitumumab plus irinotecan group. The most common adverse events in the cetuximab plus irinotecan versus panitumumab plus irinotecan groups were all-grade rash acneiform (82% versus 90%), paronychia (61% versus 52%), and grade 3-4 neutropenia (26% versus 19%). Conclusions: Panitumumab or cetuximab plus irinotecan were well tolerated and produced similar response rate and survivals compared to those previous clinical traials.These combinations are cosidered as standard treatment in patients with KRAS wild-type mCRC previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimes.

scholarly journals Phase II Study of Biweekly Pemetrexed Plus Irinotecan as Second-Line Therapy for Metastatic Colorectal Cancer

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
C. Louvet ◽  
T. André ◽  
E. Gamelin ◽  
M. Hebbar ◽  
M. Mabro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Vitamin Supplementation ◽  
Open Label ◽  
Common Grade ◽  
Duration Of Response ◽  
Grade 3

Background. This open-label, single-arm, two-stage, Phase II study investigated the efficacy and safety of bi-weekly pemetrexed combined with irinotecan, in patients with metastatic colorectal cancer (mCRC), after first-line chemotherapy using FOLFOX regimen.Patients and methods. Patients received pemetrexed 400 mg/m²as a 10-minute intravenous infusion (with vitamin supplementation) followed by irinotecan 180 mg/m²as a 90-minute infusion on day 1 of a 14-day cycle, for a maximum of 12 cycles. The primary endpoint was response rate (RR;H0≤5%,Ha≥20%,α=0.05, power = 90%). Secondary endpoints were duration of response, progression-free survival (PFS), overall survival (OS), and toxicities.Results. Partial response was observed in six out of 44 patients enrolled in the study (RR = 13.6%). The median PFS and OS were 4.0 and 13.9 months, respectively. The most common grade 3-4 toxicities were fatigue: 20.5% of patients, neutropenia: 18.6%, diarrhea: 13.6%, elevated transaminases: 9.5%, anemia: 9.3%, and vomiting: 6.8%.Conclusion. Pemetrexed plus irinotecan administered every two weeks is an active and well-tolerated regimen in mCRC patients pretreated with FOLFOX regimen. However, this regimen does not seem to provide clinically relevant advantage over historical data of a classical FOLFIRI regimen.

Lonsurf (trifluridine/tipiracil): Assessing the impact of dose related toxicities and progression free survival in (refractory) metastatic colorectal cancer

2021 ◽  
pp. 107815522110179
Author(s):  
Olivia R Court
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Dose Reduction ◽  
Progression Free Survival ◽  
Electronic Patient Records ◽  
Free Survival ◽  
Length Of Treatment ◽  
Common Grade ◽  
Grade 3 ◽  
The Impact

In the RECOURSE trial which lead to its accreditation, Lonsurf (trifluridine/tipiracil) was shown to extend progression free survival (PFS) by 1.8 months in metastatic colorectal cancer. This Trust audit aims to assess the average quantity of cycles of Lonsurf received by participants and the length of time it extends PFS. Similarly, to identify how many participants required a dose-reduction or experienced toxicities which necessitated supportive therapies. Quantitative data was collected retrospectively from all participants who had received ≥1 cycle of Lonsurf from The Clatterbridge Cancer Centre (CCC) from 2016 until June 2020. Participant electronic patient records were accessed to identify toxicity grading, length of treatment received, the date progression was identified, if dose reductions were applied and if supportive therapies were administered. Lonsurf extends PFS in patients with metastatic colorectal cancer at CCC by 3.0 months (95% CI: 2.73–3.27) and average treatment length was 2.4 months. However, 78 participants (41.5%) received a dose reduction due to toxicities. A total of 955 toxicities were recorded by participants; the most commonly reported toxicities irrespective of grade were fatigue (33.8%), diarrhoea (13.8%) and nausea (12.3%). The most common grade ≥3 toxicities were constipation and infection. The most frequently utilised supportive therapies were loperamide (49.6%) and domperidone (49.1%). Granulocyte colony stimulating factor (GCSF) was required by patients on 5 occasions (0.3%) in total. Lonsurf extends median PFS in patients with metastatic colorectal cancer by 3.0 months. The most common grade ≥3 toxicities which necessitated supportive therapies or a dose reduction were gastrointestinal and infection.

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