Elderly mCRC Patients Research Articles

Management of metastatic colorectal cancer in patients ≥70 years - a single center experience.

Age-standardized mortality rates for metastatic colorectal cancer (mCRC) are highest among elderly patients. In current clinical guidelines, treatment recommendations for this patient population are based on a limited number of clinical trials. In this monocentric, retrospective analysis we characterized patients aged ≥70 years undergoing systemic therapy for mCRC and overall survival (OS) was investigated. We included 117 unselected, consecutive mCRC patients aged ≥70 years undergoing systemic therapy for mCRC between February 2009 and July 2022. Median OS was 25.6 months (95% CI: 21.8-29.4). The median age was 78 years (range: 70-90) and 21%, 48%, 26% and 5% had an ECOG performance score of 0, 1, 2, and 3, respectively. The median number of systemic therapy lines was 2 (range: 1-5). The choice of first-line chemotherapy backbone (doublet/triplet versus mono) did not impact OS (HR: 0.83, p=0.50) or the probability of receiving subsequent therapy (p=0.697). Metastasectomy and/or local ablative treatment in the liver, lung, peritoneum and/or other organs were applied in 26 patients (22%) with curative intent. First-line anti-EGFR-based therapy showed a trend towards longer OS compared to anti-VEGF-based therapy or chemotherapy alone in left-sided mCRC (anti-EGFR: 39.3 months versus anti-VEGF: 27.3 months versus chemotherapy alone: 13.8 months, p=0.105). In multivariable analysis, metastasectomy and/or local ablative treatment with curative intent (yes versus no, HR: 0.22, p<0.001), the ECOG performance score (2 versus 0, HR: 3.07, p=0.007; 3 versus 0, HR: 3.66, p=0.053) and the presence of liver metastases (yes versus no, HR: 1.79, p=0.049) were independently associated with OS. Our findings corroborate front-line monochemotherapy in combination with targeted therapy as the treatment of choice for elderly mCRC patients with palliative treatment intent. Metastasectomy and/or local ablative treatment with curative intent are feasible and may improve OS in selected elderly mCRC patients.

First-line FOLFOX plus panitumumab versus 5FU plus panitumumab in RAS-BRAF wild-type metastatic colorectal cancer elderly patients: The PANDA study.

4002 Background: Data on first-line treatment efficacy in elderly patients are limited. Many analyses adopt a questionable cut-off of 65 years and specific evidence with anti-EGFRs is low. FOLFOX-panitumumab (pan) is an option for RAS wild-type (wt) untreated mCRC patients. Guidelines recommend considering fluoropyrimidine monotherapy as an option for elderly patients, but no randomized studies have ever explored the role of the combination with an anti-EGFR. Methods: This is a prospective, open-label, multicenter phase II randomized trial. Unresectable and previously untreated RAS- BRAF wt mCRC patients aged ≥70 were randomized to receive FOLFOX-pan (arm A), or 5FU/LV-pan (arm B) for up to 12 cycles followed by pan maintenance until PD. The primary EP was PFS in both arms. Stratification criteria were age (≤75 vs &gt; 75 years), ECOG PS (0–1 vs 2) and geriatric assessment with G8 Score (≤14 vs &gt; 14). In each treatment arm, the null hypothesis for median PFS was set at ≤6 months. Assuming an expected median PFS time ≥9.5 months with both experimental regimens, a sample size of 90 patients in each arm granted to the study a power of 90%, with a type I error rate equal to 5% (1-sided Brookmeyer-Crowley test) for rejecting the null hypothesis. No formal comparison between the two arms was planned. Results: From Jul 2016 to Apr 2019 a total of 394 patients were screened, 211 were deemed eligible for inclusion and 185 were randomized (92 arm A and 93 arm B). Main pts’ characteristics were (arm A/B): males 66%/61%; median age 77/77y; PS≥1 49%/55%; right colon 23%/21%; G8 &gt; 14 31%/30%. At a median follow up of 20.5 mos, 135 (arm A/B: 64/71) PD events were collected. Median PFS was 9.6 (95% CI 8.8-10.9) in arm A with FOLFOX-pan and 9.1 (95% CI 7.7-9.9) in arm B with 5FU/LV-pan. Response rates were (arm A/B): 65%/57%. Grade 3-4 toxicities were (arm A/B): neutropenia 9.8%/1.1%; diarrhea 16.3%/1.1%; stomatitis 9.8%/4.4%; neurotoxicity 3.3%/0%; fatigue 6.5%/4.4%; skin rash 25%/24.2%, hypomagnesemia 3.3%/7.7%. Conclusions: Large prospective randomized studies in molecularly selected elderly mCRC are feasible with multicenter collaborative efforts. Primary EP was met in both treatment arms. 5FU/LV plus panitumumab for up to 12 cycles followed by panitumumab maintenance until PD might be a reasonable option in elderly mCRC patients with RAS/BRAF wt tumors deserving further investigations in phase III trials. Clinical trial information: NCT02904031 .

Agreement between hospital discharge diagnosis codes and medical records to identify metastatic colorectal cancer and associated comorbidities in elderly patients

BackgroundQuality of coding to identify cancers and comorbidities through the French hospital diagnosis database (Programme de médicalisation des systèmes d’information, PMSI) has been little investigated. Agreement between medical records and PMSI database was evaluated regarding metastatic colorectal cancer (mCRC) and comorbidities. MethodsFrom 01/01/2013 to 06/30/2014, 74 patients aged≥65years at mCRC diagnosis were identified in Bordeaux teaching hospital. Data on mCRC and comorbidities were collected from medical records. All diagnosis codes (main, related and associated) registered into the PMSI were extracted. Agreement between sources was evaluated using the percent agreement for mCRC and the kappa (κ) statistic for comorbidities. ResultsAgreement for primary CRC and mCRC was higher using all types of diagnosis codes instead of the main one exclusively (respectively 95% vs. 53% for primary CRC and 91% vs. 24% for mCRC). Agreement was substantial (κ 0.65) for cardiovascular diseases, notably atrial fibrillation (κ 0.77) and hypertension (κ 0.68). It was moderate for psychiatric disorders (κ 0.49) and respiratory diseases (κ 0.48), although chronic obstructive pulmonary disease had a good agreement (κ 0.75). Within the class of endocrine, nutritional and metabolic diseases (κ 0.55), agreement was substantial for diabetes (κ 0.91), obesity (κ 0.82) and hypothyroidism (κ 0.72) and moderate for hypercholesterolemia (κ 0.51) and malnutrition (κ 0.42). ConclusionThese results are reassuring with regard to detection through PMSI of mCRC if all types of diagnosis codes are considered and useful to better choose comorbidities in elderly mCRC patients that could be well identified through hospital diagnosis codes.

Cost-Effectiveness of Treatment Sequences of Chemotherapies and Targeted Biologics for Elderly Metastatic Colorectal Cancer Patients.

Treatment patterns for metastatic colorectal cancer (mCRC) patients have changed considerably over the last decade with the introduction of new chemotherapies and targeted biologics. These treatments are often administered in various sequences with limited evidence regarding their cost-effectiveness. To conduct a pharmacoeconomic evaluation of commonly administered treatment sequences among elderly mCRC patients. A probabilistic discrete event simulation model assuming Weibull distribution was developed to evaluate the cost-effectiveness of the following common treatment sequences: (a) first-line oxaliplatin/irinotecan followed by second-line oxaliplatin/irinotecan + bevacizumab (OI-OIB); (b) first-line oxaliplatin/irinotecan + bevacizumab followed by second-line oxaliplatin/irinotecan + bevacizumab (OIB-OIB); (c) OI-OIB followed by a third-line targeted biologic (OI-OIB-TB); and (d) OIB-OIB followed by a third-line targeted biologic (OIB-OIB-TB). Input parameters for the model were primarily obtained from the Surveillance, Epidemiology, and End Results-Medicare linked dataset for incident mCRC patients aged 65 years and older diagnosed from January 2004 through December 2009. A probabilistic sensitivity analysis was performed to account for parameter uncertainty. Costs (2014 U.S. dollars) and effectiveness were discounted at an annual rate of 3%. In the base case analyses, at the willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life-year (QALY) gained, the treatment sequence OIB-OIB (vs. OI-OIB) was not cost-effective with an incremental cost-effectiveness ratio (ICER) per patient of $119,007/QALY; OI-OIB-TB (vs. OIB-OIB) was dominated; and OIB-OIB-TB (vs. OIB-OIB) was not cost-effective with an ICER of $405,857/QALY. Results similar to the base case analysis were obtained assuming log-normal distribution. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of $100,000/QALY gained, sequence OI-OIB was 34% cost-effective, followed by OIB-OIB (31%), OI-OIB-TB (20%), and OIB-OIB-TB (15%). Overall, survival increases marginally with the addition of targeted biologics, such as bevacizumab, at first line and third line at substantial costs. Treatment sequences with bevacizumab at first line and targeted biologics at third line may not be cost-effective at the commonly used threshold of $100,000/QALY gained, but a marginal decrease in the cost of bevacizumab may make treatment sequences with first-line bevacizumab cost-effective. Future economic evaluations should validate the study results using parameters from ongoing clinical trials. This study was supported in part by a grant from the Agency for Healthcare Research and Quality (R01-HS018956) and in part by a grant from the Cancer Prevention and Research Institute of Texas (RP130051), which were obtained by Du. The authors report no conflicts of interest. Study concept and design were primarily contributed by Parikh, along with the other authors. All authors participated in data collection, and Parikh took the lead in data interpretation and analysis, along with Lairson and Morgan, with assistance from Du. The manuscript was written primarily by Parikh, along with Lairson, Morgan, and Du, and revised by Parikh.

How are elderly patients treated after a diagnosis of metastatic colorectal cancer in real-life practice? A study in a French teaching hospital.

Metastatic colorectal cancer (mCRC) is frequent among elderly patients. However, in the era of new targeted therapies, little is known about real-life mCRC treatment in this population. This study aimed to describe elderly mCRC patients and the current real-life treatment practices. mCRC patients aged ≥65 years were identified using the registry of multidisciplinary team meetings, mandatory for all cancer patients, held between January 1, 2013 and June 30, 2014 at the Bordeaux University Hospital. Data were collected from medical records using a standardized questionnaire. Treatment type was defined as follows: at least one anticancer medication administered vs. best supportive care (BSC). A total of 78 patients were included; median age was 74 years and the M/F sex ratio 1.6. Eleven patients (14.1%) were referred to a geriatric oncology consultation. One patient died before treatment initiation, 28 (35.9%) had BSC, and 49 (62.8%) were treated with anticancer medications: 20 (25.6%) had chemotherapy combined with a targeted therapy, and 28 (35.9%) chemotherapy alone (one missing data for treatment). Compared to patients treated with anticancer medications, BSC patients were older (P < 0.0001) and had more often metachronous metastases (P = 0.01), more comorbidities (P = 0.05), and a greater number of concomitant medications (P = 0.004). This study is one of the rare investigations providing insight to treatment practices in all elderly mCRC patients, not just those who receive anticancer medications. Our results suggest that efforts must be pursued to better integrate geriatric oncology in daily clinical practice.

Age-related systemic treatment and survival of patients with metachronous metastases from colorectal cancer

Background: Although the spectrum of systemic treatment for metastatic colorectal cancer (mCRC) has widened, there is a paucity of evidence for the feasibility and optimal use of these systemic agents in elderly patients. The present study provides real world data on the age-related systemic treatment and survival of CRC patients with non-resectable metachronous metastases.Methods: All consecutive patients with non-resectable metastases from primary resected CRC were extracted from the Eindhoven area of the Netherlands Cancer Registry (NCR). Patients receiving palliative systemic therapy were enrolled (n = 385). Systemic treatment and survival were analyzed according to age at diagnosis of metastases.Results: Patients aged ≥75 years more often received first-line single-agent chemotherapy than their younger counterparts (63% vs. 32%, p < .0001). First-line single-agent chemotherapy was often prescribed without additional targeted therapy (78%). Advanced age (≥75 years) was associated with a lower probability of receiving all active cytotoxic agents compared to patients aged <60 years at time of diagnosis of metastases (odds ratio (OR) 0.2, 95% CI 0.10–0.77). In a multivariable Cox regression analysis with adjustment for age and other relevant prognostic factors, the total number of received systemic agents was the only predictor of death (hazard ratio (HR) 0.7, 95% CI 0.61–0.81).Conclusion: The beneficial effect of treatment with all active systemic agents on survival (simultaneously or sequentially prescribed) should be taken into account when considering systemic therapy in patients with mCRC. In light of our results, future studies are warranted to clarify the role of potential targeted therapy in elderly mCRC patients, who are often not candidates for combination chemotherapy and treatment with all active cytotoxic agents.

Patterns of Treatment Sequences in Chemotherapy and Targeted Biologics for Metastatic Colorectal Cancer: Findings from a Large Community-Based Cohort of Elderly Patients.

BackgroundOver the last decade, multiple chemotherapies/targeted biologics have been approved for metastatic colorectal cancer (mCRC). However, evidence is limited with regards to the array of treatments received by mCRC patients.ObjectiveThis study examines treatment sequences (first- to third-line chemotherapy/targeted biologics) and the factors associated with first-line targeted biologics and common treatment sequences for elderly mCRC patients treated in a community setting.MethodsA retrospective cohort study was conducted in mCRC patients diagnosed from January 2004 through December 2009 using the Surveillance, Epidemiology and End Results Medicare-linked database. The treatment sequences administered to elderly mCRC patients were empirically identified.ResultsOf 4418 mCRC patients who received treatment, 1370 (31 %) received first, second, and third line; 1164 (26 %) received first and second line; and 1884 (43 %) received only first line. The most common first line of treatment for mCRC patients was 5-fluorouracil/leucovorin + oxaliplatin (FOLFOX) + bevacizumab (23 %) and FOLFOX (23 %). 5-fluorouracil/leucovorin + irinotecan (FOLFIRI)-based regimens were commonly (22 %) administered in second line. The most common treatment sequence was first-line oxaliplatin or irinotecan followed by second-line oxaliplatin or irinotecan + bevacizumab followed by a third-line targeted biologic. Of patients who received first-line therapy, 47 % also received a targeted biologic, and the factors associated were age, comorbidity score, cancer site, geographic location, and year of diagnosis.ConclusionElderly mCRC patients receive a multitude of treatments in various sequences. Further exploration of the comparative effectiveness of treatment sequences may yield important information for improving mCRC survival.Electronic supplementary materialThe online version of this article (doi:10.1007/s40801-015-0059-9) contains supplementary material, which is available to authorized users.

The efficacy and safety of capecitabine plus bevacizumab combination as first-line treatment in elderly metastatic colorectal cancer patients

The optimal treatment in older persons with metastatic colorectal cancer (mCRC) is complicated by a lack of general agreement. The aim of this study was to evaluate the activity of bevacizumab plus capecitabine combination in elderly mCRC patients who were not suitable for chemotherapy with irinotecan and oxaliplatin-containing regimens. Seventy years and older patients with metastatic colorectal carcinoma were included in this retrospective study. Bevacizumab was administered at a dose of 7.5mg/kg on day 1 as an intravenous (IV) infusion over 30-90min every 21days, and capecitabine was prescribed at 1000mg/m(2) twice daily on days 1-14 of the same 21-day schedule. Eighty-two consecutive patients (47 men, 35 women) were included in the study. The mean age was 75.5 (SD 3.9, range 70-87). Half of the patients were older than 75years. There were 55 patients (67.1%) with a good Eastern Cooperative Oncology Group (ECOG) performance status (PS: 0-1) and the remaining 27 patients (32.9%) had a poor ECOG performance status (PS: 2). With a median follow-up period of 18.5months, the median progression-free survival (PFS) was 10months (95% CI, 7.8-12.1) and the median OS was 25months (95% CI, 18.6-31.3). The main toxicities recorded were non-hematological. Thirty-one patients (37%) experienced grade 3/4 adverse events, the most common being hand-foot syndrome (9.8%). No fatal toxicity resulting from this regimen was recorded. Considering the toxicity profile and survival outcomes, the combination regimen of capecitabine and bevacizumab is a potentially feasible treatment option in elderly mCRC patients.

Efficacy and safety of bevacizumab in elderly patients with metastatic colorectal cancer: results from the Czech population-based registry

BackgroundPatients aged 65 years and older represent the majority of patients with metastatic colorectal cancer (mCRC). However, this patient population is often underrepresented in clinical trials and probably undertreated in the clinical practice.MethodsWe have analysed the outcomes of 3,187 mCRC patients treated with first-line bevacizumab based on data from the Czech national registry of mCRC patients aiming to compare the treatment efficacy and safety according to the age categories.ResultsIn total, 2,126 (66.7%), 932 (29.2%), and 129 (4.0%) patients were aged <65 years, 65 to 75 years, and 75+ years, respectively. Median progression-free survival (PFS) was 11.4, 11.3, and 11.8 months for patients aged <65 years, 65 to 75 years, and 75+ years, respectively (p = 0.94). Median overall survival (OS) was 26.9, 27.5, and 25.1 months for patients aged <65 years, 65 to 75 years, and 75+ years, respectively (p = 0.73). Using multivariable Cox model for both PFS and OS, the patient age was not significantly associated with either PFS or OS. No increase in bevacizumab-related toxicity was observed among the elderly mCRC patients with the exception of hypertension, which was observed in 71 (3.3%), 34 (3.6%), and 10 (7.8%) patients aged <65 years, 65 to 75 years, and 75+ years, respectively.ConclusionsThe results of the present study suggest similar outcome in terms of OS and PFS with bevacizumab-containing therapy in elderly mCRC patients fit for chemotherapy combined with targeted therapy compared to younger patients. Thus, chronological age should not be considered to represent a limitation in prescribing bevacizumab-containing therapy in mCRC patients.

Bevacizumab (Bmab) in combination with uracil-tegafur (UFT) and oral leucovorin (LV) in elderly patients (≥ 75 years old) with metastatic colorectal cancer (mCRC): A multicenter phase II trial (J-BLUE study).

588 Background: Now fluoropyrimidine plus Bmab is considered a recommendable option to the majority of elderly mCRC patients who are deemed inappropriate for the standard doublet chemotherapy with biologics. Our previous phase II study of UFT/ LV in elderly mCRC patients (≥75 years old) had demonstrated acceptable safety and efficacy (overall response rate [ORR] 33%, progression-free survival [PFS] 5.3 months, overall survival [OS] 18 months). The aim of the present study was to investigate the efficacy and safety of Bmab in combination with UFT/LV for elderly mCRC patients. Methods: This study was designed as a single-arm, open-label, multicenter, cooperative group (SGOSG-TCTG) clinical trial (trial registration: UMIN000003515). Key eligibility criteria included age ≥75 years, ECOG performance status (PS) 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ functions. Patients received UFT 300mg/m2/day and LV 75mg/body/day on days 1-21 followed by 7 days rest, and intravenous administration of Bmab 5mg/kg on days 1 and 15. Treatment repeated every 28 days. The primary endpoint was PFS, and secondary endpoints were ORR, OS, and safety. Results: A total of 55 patients were enrolled from 15 institutions between Aug 2008 and Mar 2012. Among them, 52 eligible patients were evaluated. Median age was 80 years (range: 75-87). ECOG PS 0 was 73%. Median PFS was 8.2 months (95% confidence interval [CI], 6.2-10.3, events in 86.5%). Confirmed ORR was 40.4% (95% CI, 27.0-54.9%). Median OS was 18.7 months (95% CI, 10.3-27.0, events in 48%). The most common grade ≥3 treatment-related adverse events were hypertension (11.5%), fatigue (7.7%), nausea (5.8%), and diarrhea (5.8%). The treatment-related death occurred in 2 (3.8%) patients. Main reasons for discontinuation of treatment were disease-progression (62.5%) and toxicity (27.1%). Conclusions: Bmab in combination with UFT/LV is tolerable and effective treatment option for elderly patients (≥75 years old) with mCRC. Further trial with Bmab plus UFT/LV targeting elderly mCRC patients would be warranted. Clinical trial information: 000003515.

Bevacizumab in elderly patients with metastatic colorectal cancer

The progressively ageing population combined with an increased availability of antitumoural agents has created a new, challenging therapeutic scenario for oncologists. Due to the lack of evidence-based data on elderly patients it is uncertain whether the criteria for assessing the risk/benefit ratio of treatment strategies in these patients coincide with those classically used for the general population. A critical reevaluation of the role and potential options of systemic chemotherapy in elderly patients with metastatic colorectal cancer (mCRC) is warranted as the historical conservative approach of oncologists may have resulted in undertreatment of this patient population. Bevacizumab was demonstrated to improve the outcome of mCRC patients when used in combination with standard first and second line chemotherapy. However, its toxicity profile including hypertension, thromboembolic events, haemorrhage and proteinuria may raise important concerns when this anti-angiogenic agent is used in elderly patients with comorbidities. In this review article we analyse the available evidence on the safety and effectiveness of bevacizumab in elderly mCRC patients. Based on the data from subgroup or pooled analysis of prospective trials, observational cohort studies, retrospective population-based studies and a single recent randomised phase III trial, we conclude that the clinical benefit and safety profile of bevacizumab in elderly patients are not significantly different from those reported in younger patients, with the exception of an increased risk of arterial thromboembolic events. Bevacizumab should therefore be considered as a potential therapeutic option for elderly patients with mCRC.

Treatment Strategy for Elderly Patients with Metastatic Colorectal Cancer: A Review of the Systemic Chemotherapy Options

Despite many recent advances in the treatment of metastatic colorectal cancer (mCRC) and corresponding improvements in patient survival, most of the pivotal trials have involved fit, young patients. Consequently, it is unclear whether efficacy and safety profiles from these large randomized trials are applicable to patients older than 70 years of age, who account for more than half of those with mCRC. Most of the conclusions regarding chemotherapy for elderly mCRC patients are derived from combined or subgroup analyses from large studies in which elderly patients are typically defined as those more than 65 or 70 years of age. In general, it was concluded that, as with young patients, systemic chemotherapy could be beneficial for these elderly patients also, with tolerable adverse events. Nonetheless, it was subsequently determined that serious adverse events occurred more frequently in elderly patients and that immediate intensive chemotherapy did not always result in better overall survival for this group. In patients scheduled for capecitabine, previous estimation of renal function and careful administration of the drug are necessary; however, contrary to expectations, the quality of life is not better than that achieved with 5-fluorouracil. Another therapeutic option is immediate doublet chemotherapy, but for elderly patients, a stop-and-go strategy or chemotherapy-free intervals should be considered. Targeted agents, including bevacizumab, cetuximab, and panitumumab, have resulted in outcomes no inferior for older than for younger patients, but they require further investigation to optimize their use. The variable findings obtained for elderly patients emphasize the need for a definition of “elderly” that takes into account not only chronological age, but also physiological age, socioeconomic status, and the results of objective tools such as comprehensive geriatric assessment.

Effect of XELOX on functional ability among elderly patients with metastatic colorectal cancer: Results from the FNCLCC/GERICO 02 phase II study

Abstract Objectives This study investigated the effect of capecitabine–oxaliplatin (XELOX) on functional independence in patients aged ≥70years with histologically proven metastatic colorectal cancer (mCRC). Materials and methods Patients received capecitabine 750mg/m 2 bid d1–14+oxaliplatin 90mg/m 2 d1, every 3weeks; doses were increased to 1000 and 120mg/m 2 , respectively, in the absence of significant toxicity. The primary endpoint was stabilization/improvement of Katz Activities of Daily Living (ADL) scale. Results Sixty patients were enrolled. ADL was stabilized/improved in 36/40 patients (90%) after 3cycles, and in 25/27 patients (93%) after 6cycles. Capecitabine and oxaliplatin doses were increased in 31% of patients. The objective response rate was 37% (1 complete and 21 partial responses). Toxicity included grade 3/4 diarrhea (13%), neurotoxicity (grade 1/2 in 68%, grade 3/4 in 2%), and grade 3/4 anemia (7%). Conclusion This study demonstrates the feasibility of XELOX in elderly mCRC patients, with no impairment of independence among patients who remained on therapy.

Phase II trial of S-1 monotherapy in elderly or frail patients with metastatic colorectal cancer

A phase II study was conducted to evaluate S-1 monotherapy in previously untreated elderly or frail metastatic colorectal cancer patients. A total of 48 elderly (70-85 years old) and frail [Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 and 65-69 years old] patients were eligible for first-line S-1 of 35 mg/m(2) given twice daily for 2 weeks followed by 1 week of rest. The overall response rate (ORR) for all patients was 19%. Similarly, the ORR for frail and elderly patients was 22% and 18%, respectively. Median progression-free survival (PFS) and overall survival (OS) for all patients were 3.9 months (95% CI, 3.0-4.8) and 11.3 months (95% CI, 7.4-15.2), respectively. For frail patients, PFS was 1.4 (95% CI, 0.8-2.0) vs. 4.3 months (95% CI, 3.0-5.4) for the elderly (P = 0.016). OS was significantly longer for elderly patients than for frail patients (13.1 months, 95% CI, 9.5-16.7) vs. (4.1 months, 95% CI, 3.2-5.0; P = 0.01). Toxicity was mild to moderate, as only 29% of patients experienced grade 3 toxicity. Grade 4 toxicity and febrile neutropenia did not occur; however, two frail patients died from grade 5 treatment-related infections. Generally, S-1 monotherapy was well-tolerated and efficacious in the elderly patient group, but not in the frail patient group. Considering performance status and co-morbidities in patients >70 years old, S-1 monotherapy may be a first-line therapeutic option for elderly mCRC patients.