Does Nutritional Status Affect Treatment Tolarability, Response and Survival in Metastatic Colorectal Cancer Patients? Results of a Prospective Multicenter Study

2020 ◽  
Author(s):  
Karabulut Senem ◽  
Dogan Izzet ◽  
Cigdem Usul Afsar ◽  
Karabulut Mehmet ◽  
Sule Kahraman ◽  
...  

Abstract Background: The efficacy and tolerability of modern cytotoxic chemotherapy regimens used in malnourished metastatic colorectal cancer (mCRC) patients is uncertain. The aim of this study was to investigate the effect of malnutrition on efficacy and tolerability of cytotoxic chemotherapy and overall survival in mCRC patients.Methods: In this multicenter study, demographic, oncologic and nutritional data were collected prospectively from mCRC patients. Nutritional status of the patients were evaluated on the basis of NRI, BMI and WL before the first chemotherapy, after the first and second chemotherapy during 2 cycles of chemotherapy every 15 days. To determine the inter-treatment weight loss toxicity assessment was included to theese parameters after each chemotherapy. NRI calculation was performed as [1.51xserum albumin level (g/L)+41.7xcurrent weight/basic weight]. . NRIs were examined in 3 categories as ‘no malnutrition’ (NRI >97.5), ‘moderate malnutrition’ (97.5 ≥ NRI ≥83.5) or ‘severe malnutrition’ (NRI <83.5). Response to treatment and drug-induced toxicities were assessed based on Criteria in Solid Tumors (RECIST) 1.1 and National Cancer Institute CTCAE version 4.0 respectively.Results: One-hundred and thirty-seven mCRC patients were prospectively included. Median age was 48 (range 18-83). Primary location was colon in 66% of patients and 84% of their primary source was left colon. Malnutrition was detected in 39% of the cases. Response rate to treatment was twenty four percent. While there was no significant relationship between chemotherapy response and moderate/severe malnutrition (p=0.24), moderate/severe malnutrition was associated with multipl site of metastases, WHO PS of 1, over the median value of CEA/CA 19-9 levels (p=0.003, p=0.03, p<0.001, and p=0.02; respectively). Hypoalbuminemia and moderate/severe malnutrition were associated with all types of toxicity (p<0.001 and p<0.001). Moderate/severe malnutrition was associated with thrombocytopenia, and diarrhea following chemotherapy predominately, (p=0.02 and p=0.04; respectively). In moderate/severe malnutrition group median overall survival was prominently shorter than those with no malnutrition [6.6 moths (95%CI, 5.6-7.6) vs 11.9 moths (95% CI, 11.1-12.7) respectively, p<0.001].Conclusions: Our study showed that moderate/severe malnutrition in mCRC patients was associated with decreased overall survival and increased chemotherapy toxicity.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 70-70
Author(s):  
Senem Karabulut ◽  
İzzet Dogan ◽  
Çiğdem Usul Afşar ◽  
Mehmet Karabulut ◽  
Sule Karaman ◽  
...  

70 Background: The efficacy and tolerability of modern cytotoxic chemotherapy regimens used in malnourished metastatic colorectal cancer patients is uncertain. The aim of this study was to investigate the effect of malnutrition on efficacy and tolerability of cytotoxic chemotherapy and overall survival in mCRC patients. Methods: In this multicenter study, demographic, oncologic and nutritional data were collected prospectively from mCRC patients. Nutritional status were evaluated on the basis of NRI, BMI and WL before the first chemotherapy, after the first and second chemotherapy. To determine the inter-treatment weight loss toxicity assessment was included to theese parameters after each chemotherapy. NRIs were examined in 3 categories as ‘no malnutrition’ (NRI >97.5), ‘moderate malnutrition’ (97.5 ≥ NRI ≥83.5) or ‘severe malnutrition’ (NRI <83.5). Response to treatment and drug-induced toxicities were assessed based on RECIST 1.1 and CTCAE version 4.0 respectively. Results: 137 mCRC patients were prospectively included. Median age was 48 (range 18-83). Primary location was colon in 66% of patients, 84% of them source was left colon. Malnutrition was detected in 39% of the cases. Response rate to treatment was 24 %. Moderate / severe malnutrition was associated with multipl site of metastases, WHO PS of 1, over the median value of CEA/CA 19-9 levels (p=0.003, p=0.03, p<0.001, and p=0.02; respectively). Hypoalbuminemia and moderate/severe malnutrition were associated with all types of toxicity (p<0.001 and p<0.001). Moderate/severe malnutrition was associated with thrombocytopenia, and diarrhea following chemotherapy predominately, (p=0.02 and p=0.04; respectively). In moderate/severe malnutrition group median overall survival was prominently shorter than those with no malnutrition [6.6 moths (95 %CI, 5.6-7.6) vs 11.9 moths (95 % CI, 11.1-12.7) respectively, p<0.001]. Conclusions: Our study showed that moderate/severe malnutrition in mCRC patients was associated with decreased overall survival and increased chemotherapy toxicity.


2020 ◽  
pp. 107815522095942
Author(s):  
Senem Karabulut ◽  
Izzet Dogan ◽  
Cigdem Usul Afsar ◽  
Mehmet Karabulut ◽  
Sule Karaman ◽  
...  

Background The efficacy and tolerability of modern cytotoxic chemotherapy regimens used in malnourished metastatic colorectal cancer (mCRC) patients is uncertain. The aim of this study was to investigate the effect of malnutrition on efficacy and tolerability of cytotoxic chemotherapy and overall survival in mCRC patients. Methods In this multicenter study, demographic, oncologic and nutritional data were collected prospectively from mCRC patients. Nutritional status of the patients were evaluated on the basis of NRI (Nutritional Risk Assessment), BMI (Body Mass Index) and WL (Weight Loss) before the first chemotherapy, after the first and second chemotherapy during 2 cycles of chemotherapy every 15 days. To determine the inter-treatment weight loss toxicity assessment was included to theese parameters after each chemotherapy. NRI calculation was performed as [1.51xserum albumin level (g/L)+41.7xcurrent weight/basic weight]. NRIs were examined in 3 categories as ‘no malnutrition’ (NRI >97.5), ‘moderate malnutrition’ (97.5 ≥NRI ≥83.5) or ‘severe malnutrition’ (NRI <83.5). Response to treatment and drug-induced toxicities were assessed based on Criteria in Solid Tumors (RECIST) 1.1 and National Cancer Institute CTCAE version 4.0 respectively. Results One-hundred and thirty-seven mCRC patients were prospectively included. Median age was 48 (range 18-83). Primary location was colon in 66% of patients and 84% of their primary source was left colon. Malnutrition was detected in 39% of the cases. Response rate to treatment was twenty four percent. While there was no significant relationship between chemotherapy response and moderate/severe malnutrition (p = 0.24), moderate/severe malnutrition was associated with multipl site of metastases, WHO PS (World Health Organization Performance Status) of 1, over the median value of CEA/CA 19-9 (carcinoembryonic antigen/carbohydate antigen 19-9) levels (p = 0.003, p = 0.03, p < 0.001, and p = 0.02; respectively). Hypoalbuminemia and moderate/severe malnutrition were associated with all types of toxicity (p < 0.001 and p < 0.001). Moderate/severe malnutrition was associated with thrombocytopenia, and diarrhea following chemotherapy predominately, (p = 0.02 and p = 0.04; respectively). In moderate/severe malnutrition group median overall survival was prominently shorter than those with no malnutrition [6.6 moths (95%CI, 5.6-7.6) vs 11.9 moths (95% CI, 11.1-12.7) respectively, p < 0.001]. Conclusions Our study showed that moderate/severe malnutrition in mCRC patients was associated with decreased overall survival and increased chemotherapy toxicity.


2021 ◽  
pp. 107815522098729
Author(s):  
Senem Karabulut ◽  
Izzet Dogan ◽  
Cigdem Usul Afsar ◽  
Mehmet Karabulut ◽  
Naziye Ak ◽  
...  

Background The possible impact of malnutrition on the efficacy and tolerability of modern chemotherapy for metastatic gastic adenocarcinoma (mGC) patients is unclear. With this study, we aimed to represent the possible impact of malnutrition on the efficacy and tolerability of chemotherapy, and also on the overall survival of mGC patients. Methods In this prospective multicenter study, we collected demographic, oncological and nutritional data of our mGC patients. The nutritional status of patients were assessed with the Nutritional Risk Index (NRI), Body Mass Index (BMI) and weight loss percentage within 21-day period, between the chemotherapy cycles. All of these parameters along with toxicity assessment were evaluated after each courses of chemotherapy in order to determine inter-treatment weight loss. NRIs were calculated with a formula as follows; [1.519 × serum albumin level(g/L) + 41.7 × current weight/basic weight]. Patients were classified as having ‘no malnutrition’ (NRI > 97.5), ‘moderate malnutrition’ (97.5 ≥ NRI ≥ 83.5) or ‘severe malnutrition’ (NRI < 83.5). Drug-induced toxicities and treatment responses were evaluated via National Cancer Institute CTCAE version 4.0 and RECIST Criteria 1.1, respectively. Results One hundred and sixteen mGC patients were enrolled into the study. Median age was 60 years with range 32–83. Primary location of the tumor was antrum in 40% of the patients and of which 24% had undergone primary tumor resection. Ninety-eight percent of the patients had WHO performance status 0 or 1. Malnutrition was diagnosed in 67% of the patients and was severe in 31% of them. All patients received chemotherapy as first-line setting. Severe malnutrition was not associated with chemotherapy responses (p = 0.57). Moderate/severe malnutrition was associated with more cytopenia, nausea/vomiting, diarrhea, neuropathy, (p < 0.05 for all parameters). Moderate/severe malnutrition is associated with worser non-hematological toxicities (p = 0.038). Forty-one percent of patients died during the follow up period (Median: 138 days, range: 21–378). Malnutritional level was associated with significantly reduced overall survival. Severe malnutrition was associated with shorter median overall survival (74 days (95% CI, 20.7–111.0) vs. 237 (95% CI, 148.4-325.6) in none/moderate groups, p = 0.007). Conclusions In mGC patients, moderate/severe malnutrition is associated with worse non-hematological toxicities. Severe malnutrition is also associated with reduced overall survival.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15538-e15538
Author(s):  
Mihai Vasile Marinca ◽  
Diana Cornelia Moisuc ◽  
Bogdan Gafton ◽  
Alexa Teodora Stratulat ◽  
Petru Cianga

e15538 Background: Treatment with bevacizumab, a humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF) is known to cause adverse effects such as proteinuria, hypertension, fistulas, and thromboembolic events which, in addition to chemotherapy-induced toxicity, affect the quality of life. However, while bevacizumab-induced hypertension has been linked to increased overall survival, data on proteinuria are controversial. Methods: We performed a retrospective analysis to observe the influence of adverse effects (AEs) on the results of treatment with bevacizumab and chemotherapy in patients with metastatic colorectal cancer (mCRC). Results: Out of the 3497 mCRC patients admitted to our center between 2014 and 2019, 150 met the criteria for inclusion in our analysis. Of these, 50.7% experienced proteinuria and had reached a longer overall survival (OS, 40 versus 25 months, p = 0.015) and progression free survival (PFS, 15 versus 12 months, p = 0.039). Patients with anemia during treatment, regardless of grade, had a 20-month shorter survival. The following groups were identified as having a lower risk of death: patients with proteinuria (HR 0.630; 95% CI 0.424-0.935; p = 0.022), disease control (HR 0.436; 95% CI 0.291-0.653; p< 0.001) and non-metastatic stage at diagnosis (HR 0.477; 95% CI 0.300-0.757; p = 0.002). Anemia was a negative prognostic factor (HR 2.153; 95% CI 1.343-3.454; p = 0.001). Conclusions: Proteinuria seems to be a useful predictive factor in mCRC patients undergoing bevacizumab-based systemic therapy. Since it is already routinely assessed in this clinical setting, proteinuria could be easily integrated in the decision-making process and thus allow physicians to further individualize systemic treatments. Retrospective analyses, as our study, are setting the basis for prospective studies, required for the validation of these results.


2005 ◽  
Vol 23 (15) ◽  
pp. 3545-3551 ◽  
Author(s):  
Javier Sastre ◽  
Eugenio Marcuello ◽  
Bartomeu Masutti ◽  
Matilde Navarro ◽  
Silvia Gil ◽  
...  

Purpose Elderly patients constitute a subpopulation with special characteristics that differ from those of the nonelderly and have been underrepresented in clinical trials. This study was performed to determine the efficacy and safety of irinotecan (CPT-11) in combination with fluorouracil (FU) administered as a 48-hour continuous infusion twice a month in elderly patients. Patients and Methods Patients ≥ 72 years old with metastatic colorectal cancer, Eastern Cooperative Oncology Group performance status of 0 to 1, no geriatric syndromes, and no prior treatment were treated every 2 weeks with CPT-11 180 mg/m2 plus FU 3,000 mg/m2 in a 48-hour continuous infusion. Results By intent-to-treat analysis, in 85 assessable patients, the objective response rate was 35% (95% CI, 25% to 46%), and stable disease was 33% (95% CI, 23% to 44%). Median time to progression was 8.0 months (95% CI, 6.0 to 10.0 months), and median overall survival time was 15.3 months (95% CI, 13.8 to 16.9 months). Toxicity was moderate. Grade 3 and 4 neutropenia, diarrhea, and asthenia were observed in 21%, 17%, and 13% of patients, respectively. Only one case of neutropenic fever occurred. There were two toxic deaths, one was a result of grade 4 diarrhea and acute kidney failure, and the other was a result of massive intestinal hemorrhage in the first cycle. The study of prognostic factors did not reveal any predictive factor of response. Response to treatment and baseline lactate dehydrogenase were the main factors conditioning progression-free and overall survival. Conclusion Twice a month continuous-infusion CPT-11 combined with FU is a valid therapeutic alternative for elderly patients in good general condition.


Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 137
Author(s):  
Gianluca Mauri ◽  
Erica Bonazzina ◽  
Alessio Amatu ◽  
Federica Tosi ◽  
Katia Bencardino ◽  
...  

The BRAFV600E mutation is found in 8–10% of metastatic colorectal cancer (mCRC) patients and it is recognized as a poor prognostic factor with a median overall survival inferior to 20 months. At present, besides immune checkpoint inhibitors (CPIs) for those tumors with concomitant MSI-H status, recommended treatment options include cytotoxic chemotherapy + anti-VEGF in the first line setting, and a combination of EGFR and a BRAF inhibitor (cetuximab plus encorafenib) in second line. However, even with the latter targeted approach, acquired resistance limits the possibility of more than an incremental benefit and survival is still dismal. In this review, we discuss current treatment options for this subset of patients and perform a systematic review of ongoing clinical trials. Overall, we identified six emerging strategies: targeting MAPK pathway (monotherapy or combinations), targeting MAPK pathway combined with cytotoxic agents, intensive cytotoxic regimen combinations, targeted agents combined with CPIs, oxidative stress induction, and cytotoxic agents combined with antiangiogenic drugs and CPIs. In the future, the integration of new therapeutic strategies targeting key players in the BRAFV600E oncogenic pathways with current treatment approach based on cytotoxic chemotherapy and surgery is likely to redefine the treatment landscape of these CRC patients.


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