The impact of dose reduction and time delay in irinotecan- and oxaliplatin-based chemotherapies on outcomes in metastatic colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 631-631
Author(s):  
Naoki Mashita ◽  
Goro Nakayama ◽  
Naomi Hayashi ◽  
Chie Tanaka ◽  
Daisuke Kobayashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Time Delay ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Total Dose ◽  
Dose Reduction ◽  
Response Rate ◽  
Progression Free Survival ◽  
Disease Control Rate ◽  
Free Survival

631 Background: This study was designed to evaluate the influence of dose reduction and schedule modification on outcomes in patients with metastatic colorectal cancer (mCRC). Methods: Pooled datasets from two previous phase II trials of FOLFIRI (CCOG-0502; n = 36) and mFOLFOX6 (CCOG-0704; n = 30) in patients with mCRC were analyzed retrospectively. The RDIs of irinotecan and oxaliplatin were compared to response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). To assess the effects of dose reduction and time delay, we defined ‘dose index (DI)’ as the ratio of the actual delivered total dose to the planned total dose and ‘time index (TI)’ as the ratio of the planned duration to the actual duration of therapy. Relative dose intensity (RDI) was computed by multiplying DI by TI. DI and TI of irinotecan and oxaliplatin were compared to response rate (RR), disease control rate (DCR) and progression-free survival (PFS). Results: In patients receiving FOLFIRI therapy, the median DI and TI of irinotecan were 0.92 and 0.90, respectively. RRs were 59% vs. 12% in the higher vs. lower DI groups (p < 0.01), and 35% vs. 35% in the higher vs. lower TI groups (p = 1.00), respectively. Median PFS was 10.2 vs. 5.0 months in the higher vs. lower DI groups (p < 0.01), and 6.1 vs. 6.7 months in the higher vs. lower TI groups (p = 0.48), respectively. In mFOLFOX6 therapy, the median DI and TI of oxaliplatin were 0.97 and 0.82, respectively. RRs were 44% vs. 36% in the higher vs. lower DI groups (p = 0.65), and 44% vs. 36% in the higher vs. lower TI groups (p = 0.65), respectively. Median PFS was 7.7 vs. 6.7 months in the higher vs. lower DI groups (p = 0.13), and 8.5 vs. 5.9 months in the higher vs. lower TI groups (p = 0.02), respectively. Multivariate analyses showed that DI of irinotecan (HR 8.48; 95% CI, 2.94-24.51, p < 0.01) and TI of oxaliplatin (HR 2.74; 95% CI, 1.02-7.33, p = 0.04) were the independent prognostic factors for PFS. Conclusions: Dose reductions in irinotecan and time delays in oxaliplatin could have significant impact on PFS in patients receiving FOLFIRI and FOLFOX6, respectively.

Apatinib monotherapy for chemotherapy-refractory metastatic colorectal cancer: A multicenter, single-arm, prospective study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3527-3527 ◽  
Author(s):  
Fen Wang ◽  
Shubin Wang ◽  
Xia Yuan ◽  
Jun Jia ◽  
Xiaoxia Bi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prospective Study ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Disease Control Rate ◽  
Free Survival

3527 Background: Apatinib is an oral highly-selective tyrosine kinase inhibitor (TKI) that blocks vascular endothelial growth factor receptor 2 (VEGFR-2). This exploratory study evaluated the efficacy and safety of apatinib monotherapy in patients with chemotherapy-refractory metastatic colorectal cancer. Methods: In this multicenter, single-arm, prospective study, 48 patients with metastatic colorectal cancer who had failed at least two lines standard chemotherapies including fluorouracil, oxaliplatin and irinotecan were recruited from 14 centers in Guangdong, China. Apatinib at a 500mg dose was administered daily continuously. Each cycle was 4 weeks (28 days). The primary endpoint was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and toxicity. Results: A total of 48 patients was enrolled in the study from September 3, 2015 to June9, 2017. Four patients achieved a partial response, and 22 achieved stable disease, representing a response rate of 8.3% and a disease control rate of 60.4%. Median follow-up time was 10.3 months. Median progression-free survival (PFS) and overall survival (OS) of evaluable patients (n=41) were 4.7 months (95% confidence interval [CI] 3.7-5.9) and 9.7 months (95% CI 5.9-13.6). The most common grade 3 or 4 adverse events (AE) were hypertension (12.5%), hand-foot syndrome (10.4%), thrombocytopenia (10.4%), proteinuria (8.3%) and mucositis oral (6.3%). Conclusions: Apatinib monotherapy shows promising efficacy and manageable toxicities in patients with chemotherapy-refractory metastatic colorectal cancer. Further phase 3 trial is warranted. Clinical trial information: ChiCTR1900020503.

scholarly journals Inflammatory Markers Predict Survival in Patients With Advanced Gastric and Colorectal Cancers Receiving Anti–PD-1 Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaona Fan ◽  
Dan Wang ◽  
Wenjing Zhang ◽  
Jinshuang Liu ◽  
Chao Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Disease Control ◽  
Inflammatory Markers ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Disease Control Rate ◽  
Free Survival ◽  
Lymphocyte Ratio

There is a lack of useful biomarkers for predicting the efficacy of anti–programmed death-1 (PD-1) therapy for advanced gastric and colorectal cancer. To address this issue, in this study we investigated the correlation between inflammatory marker expression and survival in patients with advanced gastric and colorectal cancer. Data for 111 patients with advanced gastric and colorectal cancer treated with anti–PD-1 regimens were retrospectively analyzed. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and clinical characteristics of each patient were selected as the main variables. Overall response rate, disease control rate, and progression-free survival were primary endpoints, and overall survival and immune-related adverse events (irAEs) were secondary endpoints. The chi-squared test and Fisher’s exact test were used to evaluate relationships between categorical variables. Uni- and multivariate Cox regression analyses were performed, and median progression-free survival and overall survival were estimated with the Kaplan–Meier method. The overall response rate and disease control rate of anti–PD-1therapy in advanced gastric and colorectal tumors were 12.61 and 66.66%, respectively. The patients with MLR &lt; 0.31, NLR &lt; 5, and PLR &lt; 135 had a significantly higher disease control rate than those with MLR &gt; 0.31, NLR &gt; 5, and PLR &gt; 135 (P &lt; 0.05). The multivariate analysis revealed that MLR &lt; 0.31, BMI &gt; 18.5, and anti–PD-1 therapy in first-line were associated with prolonged PFS. MLR &lt; 0.31 and BMI &gt; 18.5 were associated with prolonged overall survival. The irAE rate differed significantly between PLR groups, and PLR &lt; 135 was associated with an increased rate of irAEs (P = 0.028). These results indicate that the inflammatory markers NLR, MLR, and PLR have clinical utility for predicting survival or risk of irAEs in patients with advanced gastric cancer and colorectal cancer.

scholarly journals Phase II study of lenvatinib for metastatic colorectal cancer refractory to standard chemotherapy: the LEMON study (NCCH1503)

ESMO Open ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. e000776 ◽  
Author(s):  
Satoru Iwasa ◽  
Natsuko Okita ◽  
Aya Kuchiba ◽  
Gakuto Ogawa ◽  
Mamiko Kawasaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Growth Factor ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Disease Control Rate ◽  
Vegf Receptor ◽  
Free Survival

BackgroundLenvatinib inhibits tyrosine kinases, including vascular endothelial growth factor (VEGF) receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor alpha, RET proto-oncogene and KIT proto-oncogene, receptor tyrosine kinase. We assessed the efficacy and safety of lenvatinib in patients with metastatic colorectal cancer after failure of standard chemotherapies.Patients and methodsThis was an open-label, single centre, single-arm, phase 2 study. Eligible patients had unresectable metastatic colorectal adenocarcinoma, refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, trifluridine/tipiracil, anti-VEGF therapy and anti-epidermal growth factor receptor therapy (for tumours with wild-type RAS). Patients were treated with oral lenvatinib at 24 mg one time a day in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was centrally assessed disease control rate. Secondary endpoints included safety, response rate, progression-free survival and overall survival. The planned sample size was 30 patients to expect a disease control rate of 60% with a threshold disease control rate of 35%, one-sided alpha of 5% and power of 80%ResultsBetween 24 October 2016 and 23 January 2018, 30 patients were enrolled; 11 (37%) and 19 (63%) had received 3 or ≥4 lines of prior chemotherapy for metastatic disease, respectively. The median number of lenvatinib cycles was 4 (range 1–13). The centrally assessed disease control rate was 70.0% (21/30, 90% CI 53.5% to 83.4%, one-sided p=0.0001); 2 patients had a partial response and 19 had a stable disease. Median progression-free survival was 3.6 months (95% CI 2.6 to 3.7). Median overall survival was 7.4 months (95% CI 6.4 to 10.8). The most common grade ≥3 adverse events were hypertension (53%), thrombocytopenia (10%), increased alanine aminotransferase and anorexia (7% each).ConclusionsLenvatinib showed promising clinical activity and was tolerated in patients with metastatic colorectal cancer after failure of standard chemotherapies.Trial registration numberUMIN-CTR, UMIN000023446 and JAMCCT-CTR, JMA-IIA00261.

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.

Phase II study of combination chemotherapy with biweekly cetuximab and irinotecan for wild-type KRAS metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 561-561
Author(s):  
S. Yuki ◽  
K. Shitara ◽  
M. Yoshida ◽  
D. Takahari ◽  
S. Utsunomiya ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Combination Chemotherapy ◽  
Response Rate ◽  
Standard Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Wild Type ◽  
Standard Regimen ◽  
Free Survival

561 Background: Weekly cetuximab and irinotecan is a standard regimen in heavily pretreated patients with metastatic colorectal cancer (MCRC). The aim of this study was to prospectively evaluate the efficacy of combination chemotherapy with biweekly cetuximab and irinotecan in patients with pretreated MCRC harboring wild-type KRAS. Methods: Patients with wild- type KRAS MCRC that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included in this study. Cetuximab was administered at 500 mg/m2 biweekly with irinotecan. The primary endpoint was response rate. The secondary endpoints included adverse events, progression-free survival, and overall survival. The pharmacokinetics of cetuximab was also evaluated in five patients. Results: From May, 2009 to February, 2010, a total of 31 patients were enrolled from five institutions. One patient was not eligible. Among the 30 assessable patients, ECOG PS was 0 in 12, 1 in 16, and 2 in two patients. The objective response rate was 30.0% (95% confidence interval [CI], 14.7-49.4), and the disease control rate (complete response, partial response, or stable disease) was 76.7% (95%CI, 61.4-92.3). The median progression-free survival was 5.3 months (95%CI, 3.4-7.3). Grade 3 skin toxicity was observed in 3 patients (10%), and treatment related death due to pneumonia occurred in one patient. Conclusions: The efficacy data are similar to those of standard dose of cetuximab plus irinotecan. Combination chemotherapy with biweekly cetuximab and irinotecan is effective for pretreated metastatic wild-type KRAS MCRC. No significant financial relationships to disclose.

Effect of the addition of bevacizumab to first-line FOLFOX on efficacy, including response rate, progression-free survival, and overall survival, in patients with metastatic colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 588-588
Author(s):  
M. Suenaga ◽  
N. Mizunuma ◽  
S. Matsusaka ◽  
E. Shinozaki ◽  
M. Ogura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Survival Benefit ◽  
Response Rate ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

588 Background: Bevacizumab (BV) is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor. Used in combination with chemotherapy, BV has been shown to improve survival in both first- and second-line treatment for metastatic colorectal cancer (mCRC). However, it was reported that addition of BV to FOLFOX conferred only little survival benefit (Saltz et al. JCO2008). The aim of this study was to assess the efficacy of addition of BV to FOLFOX in first-line treatment for patients with mCRC. Methods: Bevacizumab was approved for mCRC in July 2007 in Japan. This study was conducted at a single institution and comprised 217 consecutive patients receiving first-line treatment for mCRC between 2005 and 2009. The primary objective was to compare survival benefit in patients treated with FOLFOX4 (FF) between 2005 and 2007 with that in patients receiving FOLFOX4+BV 5 mg/kg (FF+BV) between 2007 and 2009. Results: Total number of patients in the FF and FF+BV groups was 132 and 85, respectively. Characteristics of patients were as follows (FF vs. FF+B): median age, 62 yrs (range 28-76 yrs) vs. 60 yrs (range16-74 yrs); ECOG PS0, 98.8% vs. 81.8%; and median follow-up time, 20.8 months vs. 24.4 months. Median progression-free survival (PFS) in the FF and FF+BV groups was 10 months (95% CI, 8.7-11.3) and 17 months (95% CI, 10.2-14.1), while median overall survival (OS) was 21 months (95% CI, 17.9-24.1) and not reached, respectively. Response rate was 46% (95% CI, 37- 54) in FF, and 62% (95% CI, 51-73) in FF+BV. Addition of BV to FOLFOX4 significantly improved PFS (p=0.002) and OS (p<0.001). Conclusions: The additive effect of BV for first-line FOLFOX was reconfirmed. These data indicate potential survival benefits from the addition of BV to FOLFOX in first-line treatment of mCRC. In addition, PFS may be a sensitive indicator of outcome prior to post-treatment. No significant financial relationships to disclose.

A phase II trial of trastuzumab combined with irinotecan in patients with advanced HER2-positive chemo-refractory gastric cancer: OGSG1203 (HERBIS-5).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 128-128 ◽  
Author(s):  
Kazuhiro Nishikawa ◽  
Daisuke Sakai ◽  
Junji Kawada ◽  
Ryohei Kawabata ◽  
Tomono Kawase ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Disease Control ◽  
Intravenous Infusion ◽  
Response Rate ◽  
Progression Free Survival ◽  
Disease Control Rate ◽  
Efficacy And Safety ◽  
Her2 Positive ◽  
Free Survival

128 Background: Irinotecan is a key drug in second- or further-line chemotherapy for patients with advanced gastric cancer. Continuous administration of trastuzumab beyond first progression is expected to contribute to the benefit of chemotherapy for HER2-positive gastric cancer. We assessed the efficacy and safety of combination chemotherapy with trastuzumab and irinotecan in Japanese patients with advanced HER2-positive chemo-refractory gastric cancer. Methods: Intravenous infusion of irinotecan every 2 weeks at a dose of 150 mg/m2; intravenous infusion of trastuzumab at a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. Administration of irinotecan and trastuzumab were repeated in independent schedules. The primary endpoint was disease control rate. The secondary endpoints were adverse events, response rate, time-to-treatment failure, progression-free survival, overall survival, and response rate stratified by prior trastuzumab use. This study was conducted by the Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG). Results: From October 2012 to Augst 2014, 30 patients were enrolled and one patient withdrew before study treatment. Accordingly, 29 patients were assessable for efficacy and safety. The disease control rate was 65.5% [95% C.I. 45.7 - 82.1%], and the response rate was 20.7% [95% C.I. 8.0 - 39.7%]. The median progression free survival and the median overall survival were 3.7 and 7.5 months, respectively. The major grade 3/4 toxic effects were neutropenia (24%); anemia (24%); leucopenia (21%); anorexia (11%); fatigue (14%); hypoalbuminemia (24%); and hypokalemia (14%). One death (NOS) was considered to be related to the study. Conclusions: The results of combination Trastuzumab with irinotecan showed feasible and promising efficacy against advanced HER2-positive chemo-refractory gastric cancer. These findings indicated that trastuzumab continuation use might be beneficial. Clinical trial information: 000008626.

Cetuximab Plus Various Chemotherapy Regimens for Patients with KRAS Wild-Type Metastatic Colorectal Cancer

Chemotherapy ◽  
2015 ◽  
Vol 61 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Payam Azadeh ◽  
Nafiseh Mortazavi ◽  
Arezoo Tahmasebi ◽  
Farnaz Hosseini Kamal ◽  
Kambiz Novin
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
The Other ◽  
Hematologic Toxicity ◽  
Wild Type ◽  
Standard Chemotherapy ◽  
Free Survival

Background: The aim of this study was to compare the efficacy and hematologic toxicity of cetuximab combined with various types of chemotherapy regimens in patients with KRAS wild-type metastatic colorectal cancer (mCRC). Methods: The response rate, progression-free survival (PFS) and overall survival of the patients were analyzed. Results: In total, 45 patients were included in the study. The overall response rate for the combination of cetuximab and FOLFOX, FOLFIRI and CAPOX was 20, 46 and 30%, respectively, but the differences were not statistically significant. The median PFS for the three groups were 8, 6 and 3.5 months, respectively, but again these differences were not significant. All-grade leukopenia and anemia for the cetuximab plus FOLFOX group were significantly higher than for the other chemotherapy regimens. Conclusion: Our findings suggest that the combination of cetuximab and the three standard chemotherapy regimens resulted in the same outcomes in our patient population of mCRC, with higher hematologic toxicities among the FOLFOX subgroup.

scholarly journals Сonfirmatory study of the efficacy and tolerability of trifluridine/tipiracil (TAS-102) therapy in the Russian population with chemorefractory metastatic colorectal cancer

2020 ◽  
pp. 47-52
Author(s):  
M. Yu. Fedyanin ◽  
F. V. Moiseenko ◽  
D. A. Chekini ◽  
V. A. Chubenko ◽  
A. S. Zhabina ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Rate ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Colon Adenocarcinoma ◽  
Progression Free Survival ◽  
Russian Population ◽  
Open Label ◽  
Free Survival ◽  
Efficacy Criteria

Introduction. Trifluridine/Tipiracil (FTD/TPI) is a new chemotherapeutic drug approved in more than 60 countries for use in patients with metastatic colorectal cancer who have registered progression or intolerance to treatment with fluoropyrimidines, oxaliplatin and irinotecan, anti-VEGRand anti-EGFR-targeted agents. This study evaluated for the first time the effectiveness and tolerability of FTD/TPI therapy in the Russian patient population.Materials and methods. A confirmatory open-label single-arm non-randomized trial was conducted in 2 clinical centres in Russia. The main criteria for inclusion were: conduction of at least the 2nd line of standard systemic therapy for metastatic colon adenocarcinoma. The primary efficacy criteria were: 2-month progression-free survival; secondary – median progressionfree survival, disease control frequency, safety assessment, overall survival. Research number: NCT03274882.Results. A total of 26 patients were included in the study; the median age was 60.5 years (30 to 78); 19 (73%) women; and 4 patients with ECOG 0 and 22 – with ECOG 1. All patients were previously treated with the inclusion of oxaliplatin, irinotecan, fluoropyrimidines, 21 (81%) – bevacizumab, 6 (23%) – anti-EGFR antibodies, and 2 (7.7%) – regorafenib. The median for treatment courses was 4 (1–21), 11 (42.3%) patients were treated for 6 months or more. The two-month progression-free survival rate was 52% with a median progreesion-free survival rate of 4 months (95% CI 1.8–7.4 months). The median of total survival rate was 11 months (95% CI 5,2–16,8 months). Disease control was achieved in 60%. Neutropenia, nausea, vomiting, anemia, weakness prevailed among undesirable events associated with treatment (≥5 patients). The majority of complications were of the 1st–2nd degree. Among the undesirable events of the 3rd–4th degree, neutropenia was more common, while in 3 patients febrile neutropenia of the 3rd degree was registered.Conclusions. In the Russian population of patients with colorectal chemorefractory cancer, the drug FTD/TPI (TAS-102) shows efficacy and tolerability comparable to the RECOURSE registration study.

A phase II trial of panitumumab with irinotecan and S-1 (IRIS) as second-line treatment in patients with wild-type KRAS metastatic colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 732-732
Author(s):  
Rai Shimoyama ◽  
Tetsuo Kimura ◽  
Toshi Takaoka ◽  
Kazuki Sakamoto ◽  
Shunji Kawamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Second Line ◽  
Wild Type ◽  
Free Survival ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

732 Background: Panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in second-line chemotherapy increased objective response rate and prolonged progression-free survival (PFS) versus FOLFIRI alone in patients with wild-type (WT) KRAS metastatic colorectal cancer (mCRC) (Peeters et al, J Clin Oncol 2010). This trial (UMIN000004659) evaluated tolerability and efficacy of combination therapy with irinotecan and S-1, an oral fluoropyrimidine (IRIS) plus panitumumab as second-line chemotherapy in patients with WT KRASmCRC. Methods: Main inclusion criteria were: patients with WT KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥20 years. Patients received panitumumab (6 mg/m2) and irinotecan (100 mg/m2) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was completion rate of protocol therapy (CRT). The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS). Results: Thirty-seven patients were enrolled in 9 centers. The overall CRT was 62.2% (23/37). Most frequent grade 3/4 toxicities were: skin rash (24%), diarrhea (16%), and appetite loss (11%). The overall RR was 32.4% (12/37). Of these, four patients underwent conversion surgery. Median PFS and OS were 9.5 months (95% CI: 3.5-15.4 months) and 20.1 months (95% CI: 16.7-23.2 months), respectively. Conclusions: IRIS plus panitumumab has acceptable toxicity profile and promising efficacy in patients with previously treated WT KRAS mCRC. This regimen can be an additional treatment option for second-line chemotherapy in WT KRAS mCRC. Clinical trial information: UMIN000004659.

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