Reduction of derived neutrophil-to-lymphocyte ratio after four weeks predicts the outcome of patients receiving second-line chemotherapy for metastatic colorectal cancer

Background: BRAF (v-raf murine sarcoma viral oncogene homolog B1) V600E mutant colorectal cancer is associated with short survival. Recently, clinical trials have been conducted to improve outcomes of second or later lines of chemotherapy. However, there is a paucity of reference data pertaining to outcomes of second-line chemotherapy and prognostic factors that are relevant only to BRAF mutant patients. Patients and methods: We retrospectively reviewed metastatic colorectal cancer patients with BRAF V600E mutation who underwent second-line chemotherapy between January 2007 and March 2017. We evaluated treatment outcomes and performed prognostic analyses. Results: A total of 52 patients were included. The median progression-free survival and overall survival (OS) were 2.5 [95% confidence interval (CI) = 1.91–4.11] and 6.5 (95% CI = 4.30–9.63) months, respectively. Overall response and disease control rates were 7% and 48%, respectively. All the regimens which elicited a partial response included BRAF inhibitors in combination with anti-epidermal growth factor receptor (EGFR) antibodies. Therefore, the overall response was 0% after exclusion of patients treated with study drugs. Multivariate analysis for OS revealed that the Glasgow Prognostic Score (GPS), elevated lactate dehydrogenase, and poor performance status were independent prognostic factors. In particular, survival curves according to the GPS stratified the patients into distinct risk groups. The median OSs in patients with GPS of 0, 1, and 2 were 9.9, 5.0, and 1.9 months, respectively. Conclusions: Outcomes of second-line chemotherapy for metastatic colorectal cancer patients with BRAF V600E mutation were extremely poor. GPS may be useful in future clinical trials.

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A multinational, randomized, phase III trial of XELIRI (+bevacizumab) versus FOLFIRI (+bevacizumab) as the second-line chemotherapy for metastatic colorectal cancer: Asian XELIRI project (AXEPT).

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.tps780 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. TPS780-TPS780 ◽

Cited By ~ 3

Author(s):

Kei Muro ◽

Tae Won Kim ◽

Young Suk Park ◽

Hiroyuki Uetake ◽

Tomohiro Nishina ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Trial ◽

Metastatic Colorectal Cancer ◽

Performance Status ◽

Dose Intensity ◽

Phase Iii ◽

Second Line ◽

Second Line Chemotherapy ◽

Clinical Trial Information ◽

Line Chemotherapy

TPS780 Background: Life-prolonging systemic therapy such as chemotherapy (FOLFOX, XELOX, FOLFIRI, 5-FU/LV) with / without molecular targeted agents (bevacizumab, afilibercept, cetuximab, panitumumab) are important treatment for metastatic colorectal cancer (mCRC). On the other hand, it is required to establish an evidence of convenient therapy including oral anticancer agent which is expected lower risk of safety. XELIRI was already examined by various doses in this decade, and result of AIO 0604 was regarded as one of the most appropriate regimen. The BIX phase II study showed the tolerability and promising efficacy of the AIO regimen for Japanese mCRC patients (Hamamoto Y, et al. Oncologist 2014). Methods: Asian XELIRI Project (AXEPT) is an East Asian collaborated, open label, randomized phase III clinical trial designed to demonstrate the non-inferiority of XELIRI (+bevacizumab) to the standard of care FOLFIRI (+bevacizumab) as the second-line chemotherapy in patients with mCRC. The primary endpoint is median overall survival. The secondary endpoints are progression-free survival, time to treatment failure, overall response rate, disease control rate, relative dose intensity, safety, correlation between UGT1A1 polymorphisms (*28, *6) and safety. Eligible patients were 20 years of age and older, had histologically proven CRC, ECOG performance status 0-2, adequate organ function, progression or difficult to continue after first line regimen. Patients were randomized 1:1 to standard FOLFIRI (+bevacizuamb 5mg/kg day1), repeated every 14 days (Group A) or XELIRI, Irinotecan 200mg/m2 day1, and capecitabine 1600mg/m2 day 1-14 (+bevacizumab 7.5mg/kg day1), repeated every 21 days (Group B). A Total of 464 events were needed to show non-inferiority with a two-sided α of 0·05 and a power of 80%, a target sample size of 600 patients was required. (The 95% CI upper limit of the hazard ratio was pre-specified as less than 1.3.). Enrollment has started in December 2013. As of August 2015, 98 centers in the Japan, South Korea and China are participating in this trial. Clinical trial information: NCT01996306. UMIN000012263. Clinical trial information: NCT01996306.

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Safety and antitumor activity of arsenic trioxide plus infusional 5-fluorouracil, leucovorin, and irinotecan as second-line chemotherapy for refractory metastatic colorectal cancer: A pilot study from South India

Indian Journal of Cancer ◽

10.4103/ijc.ijc_374_17 ◽

2017 ◽

Vol 54 (4) ◽

pp. 631

Author(s):

Tamojit Chaudhuri ◽

KC Lakshmaiah ◽

GovindK Babu ◽

Dasappa Lokanatha ◽

LinuAbraham Jacob ◽

...

Keyword(s):

Colorectal Cancer ◽

Pilot Study ◽

Antitumor Activity ◽

Metastatic Colorectal Cancer ◽

Arsenic Trioxide ◽

South India ◽

Second Line ◽

Second Line Chemotherapy ◽

Line Chemotherapy

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Correction to: S-1 and irinotecan plus bevacizumab as second-line chemotherapy for patients with oxaliplatin-refractory metastatic colorectal cancer: a multicenter phase II study in Japan (KSCC1102)

International Journal of Clinical Oncology ◽

10.1007/s10147-017-1212-0 ◽

2017 ◽

Vol 23 (2) ◽

pp. 402-402

Author(s):

Yuji Miyamoto ◽

Akihito Tsuji ◽

Hiroaki Tanioka ◽

Soichiro Maekawa ◽

Hirofumi Kawanaka ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Second Line ◽

Second Line Chemotherapy ◽

Multicenter Phase ◽

Line Chemotherapy

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Neutrophil-lymphocyte Ratio at the Beginning of Third-line Chemotherapy Seems to be a Useful Predictor for Unresectable Colorectal Cancer

10.21203/rs.3.rs-65337/v1 ◽

2020 ◽

Author(s):

Hidejiro Kawahara ◽

Nobuo Omura ◽

Tadashi Akiba

Keyword(s):

Colorectal Cancer ◽

Primary Tumor ◽

Second Line ◽

Primary Tumor Site ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Second Line Chemotherapy ◽

Third Line ◽

One Year ◽

Line Chemotherapy

Abstract Aim: This study aimed to evaluate a long-term outcome predictor after second-line chemotherapy for unresectable colorectal cancer.Methods: Between 2013 and 2018, sixteen patients (twelve males, four females) with unresectable colorectal cancer who were administered TAS-102 as third-line chemotherapy in our institution were retrospectively enrolled in this study. The mean age was 65.4 (range: 46-79) years. Patients were administered oxaliplatin with oral S-1 (tegafur, gimeracil, oteracil potassium) (SOX) as first-line chemotherapy followed by irinotecan with oral S-1 (IRIS) as second-line chemotherapy.Results: The median survival time after second-line chemotherapy was 19.2 months. Significant differences in mean age, gender, body mass index, primary site of disease, pathology of primary tumor, depth of primary tumor invasion, serum carcinoembryonic antigen (CEA) level, serum carbohydrate antigen 19-9 (CA19-9) level, and recurrence site of disease were not observed between patients with less than one year of survival versus greater than one year of survival. However, neutrophil-lymphocyte ratio (NLR) at the beginning of third-line chemotherapy was the only factor of the ten evaluated that exhibited a significant difference. Primary tumor site (p=0.015) and NLR at the beginning of third-line chemotherapy (p=0.010) were independent contributing factors to predict survival after second-line chemotherapy based on Cox proportional hazards regression.Conclusion: NLR at the beginning of third-line chemotherapy is a useful predictor for unresectable colorectal cancer after second-line chemotherapy.

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