Effect of cancer cachexia on treatment toxicity in metastatic colorectal cancer patients: Results of a prospective multicenter study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9026-9026 ◽  
Author(s):  
Maximilien Barret ◽  
Cecile Dalban ◽  
Julien Taïeb ◽  
David Malka ◽  
Touraj Mansourbakht ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Muscle Tissue ◽  
Clinical Evaluation ◽  
Multicenter Study ◽  
Whole Body ◽  
Cross Sectional ◽  
Chemotherapy Toxicity ◽  
Number Of Patients ◽  
Grade 3

9026^ Background: Malnutrition reduces tolerance to treatment and survival in numerous cancers, including metastatic colorectal cancer (mCRC). Previous studies have shown that chemotherapy toxicity may be linked to sarcopenia. We evaluated the effect of sarcopenia on chemotherapy toxicity among mCRC patients. Methods: In this prospective, cross-sectional, multicenter study, oncological and nutritional data were collected in all consecutive mCRC patients between March 7th and March 20th 2005 in three hospitals. Computed tomography (CT) images were analysed using Slice-O-Matic software V4.3 (Tomovision) to evaluate cross-sectional areas (cm2) of muscle tissue (MT), visceral and subcutaneous adipose tissue (VAT and SAT). The 3rd lumbar vertebra (L3) was chosen as a reference, since L3 and whole-body measurements are linearly related. Indexed on height, MT, VAT and SAT (cm2/m2), were computed and described, after stratification on sex. In accord with the literature, sarcopenia was defined as MT <55 cm2/m2 for men and <39 cm2/m2 for women. Images were obtained within one month of clinical evaluation. Toxicities were evaluated according to the NCI-CTC, version 3.0, in the two months following clinical evaluation. Results: 53 mCRC patients (72% men (M)), participated in the study. According to body mass index (BMI) only 7% of female patients (F) and 3% M were malnourished (BMI<17 kg/m²), and 93% F and 97% M were of normal weight or overweight (BMI> 25kg/m²). These results are to be compared to the 38% (F) and 82% (M) of patients with sarcopenia. Grade 3-4 toxicities were observed in 28% of the cases, with neurotoxicity in 6%, diarrhea 2%, anemia 2%, neutropenia 9%, and nausea and vomiting 6%. In multivariate analysis including age, sex, BMI, sarcopenia, SAT and VAT, the only factor associated with grade 3-4 toxicity was sarcopenia (OR= 13.55 95% CI [1.08;169.31], p=0.043). Conclusions: In mCRC patients undergoing chemotherapy, low muscle tissue was much more frequently observed (68%) than “visible” malnutrition (4%). Despite the small number of patients included in our study, we showed that sarcopenia was associated with severe chemotherapy toxicity in mCRC.

Pharmacogenetic analysis of toxicity after 5-fluorouracil (5FU) or 5FU/oxaliplatin therapy for metastatic colorectal cancer: Preliminary results in FFCD 2000–05 trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2508-2508
Author(s):  
M. Castaing ◽  
M. A. Loriot ◽  
M. Barrois ◽  
I. Miran ◽  
C. Mulot ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
First Line ◽  
Fragment Analysis ◽  
Blood Samples ◽  
Preliminary Results ◽  
Number Of Patients ◽  
Grade 3 ◽  
Interaction Test ◽  
Predictive Effect

2508 Background: The FFCD 2000–05 randomized trial compared simplified LV5FU2 followed by FOLFOX6 (arm 1) to FOLFOX6 followed by FOLFIRI (arm 2) in the treatment of metastatic colorectal cancer. The aim was predicting the toxicity profile of oxaliplatin after the first line treatment using pharmacogenetic data. Methods: Patients (pts) with available blood samples were compared to the other pts for clinical prognostic factors (chi2 test). A logistic model was computed to test the association between polymorphisms and toxicity in each arm. An interaction test was used to assess a differential effect according to treatment (predictive effect), in order to identify a predictive effect of oxaliplatin. Grade 3–4 hematological and non-hematological toxicities (H-tox and NH-tox) at 4 months and grade 2–4 neurological at 6 months were the endpoints of the study. Thirteen genetic variants in 10 candidate genes were selected for pharmacogenetic analysis: ERCC1_04 (rs3212961), ERCC1_05 (rs11615), ERCC1_06 (rs3212948), ERCC1_24 (rs3212955), ERCC2_02 (rs1799793), ERCC2_03 (rs13181), ERCC2_06 ( rs238406 ), ERCC2_09 (rs1799787), GSTM1 (null/present), GSTT1 (null/present), TS (TSER, Ins/del6bp) and UGT1A1 (rs8175347). Genotyping was performed using Taqman probes, QMPSF and fragment analysis. Results: 327 pts (156/171) out of 410 were included (61 had no blood samples, 16 had less than 2 cycles, 3 had incomplete data on toxicity, 3 had insufficient DNA). No difference was found between included and excluded pts in the analysis for gender, age, OMS, number of metastatic organs and adjuvant chemotherapy. Pts received similar 5FU doses in both arms. Number of patients with at least one toxicity in arms 1/2 were as followed: 5/54 grade 3–4 H-tox, 28/47 grade 3–4 NH-tox, and 0/103 grade 2–4 neurological. The genotype CC of ERCC2_02 correlated with higher NH-tox at 4 months in arm 2 (p=0.0008, OR=0.31, 95%CI=[0.15–0.62] versus p=0.87, OR=0.93, CI=[0.39–2.21] in arm 1) compared to genotypes CT and TT, with borderline interaction (p=0.05). Conclusions: These preliminary results on early toxicity in first-line are in favour of an effect of ERCC2_02 on NH-tox of FOLFOX6 and a predictive effect on NH-tox of oxaliplatin. [Table: see text]

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.

Quadruplet regimen with capecitabine, irinotecan, oxaliplatin, and bevacizumab in chemo-naive patients with metastatic colorectal cancer: Results from the safety lead-in of QUATTRO-II study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 57-57
Author(s):  
Hideaki Bando ◽  
Daisuke Kotani ◽  
Masahito Kotaka ◽  
Akihito Kawazoe ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Braf V600e ◽  
Phase Iii ◽  
Fixed Dose ◽  
Wild Type ◽  
Randomized Phase Ii ◽  
Level 1 ◽  
Grade 3

57 Background: FOLFOXIRI plus bevacizumab (BEV) is regarded as the standard of care for selected patients (pts) with metastatic colorectal cancer (mCRC), despite the high incidence of neutropenia and diarrhea. The AXEPT phase III study showed that the modified capecitabine (CAP) + irinotecan (IRI) + BEV (CAPIRI+BEV) [CAP 1600 mg/m2, IRI 200 mg/m2, and BEV 7.5 mg/kg q3wk] treatment was non-inferior to FOLFIRI+BEV, with a lower incidence of hematologic toxicity. We hypothesized that the modified CAPIRI combined with oxaliplatin (OX) and BEV (CAPOXIRI+BEV) would be more feasible than FOLFOXIRI+BEV, without compromising efficacy. Methods: The QUATTRO-II study is an open-label, multicenter, randomized phase II study. In Step 1, the recommended doses (RD) of OX and IRI were investigated as a safety lead-in. In Step 2, pts are randomized to either the RD of CAPOXIRI+BEV or FOLFOXIRI+BEV. In Step 1, four dose levels of CAPOXIRI (fixed dose of CAP 1600 mg/m2 and BEV 7.5 mg/kg plus escalated or de-escalated doses of OX and IRI, q3wk) were investigated in a 3+3 manner. A dose level of ≤ 2/6 of dose-limiting toxicity (DLT) cases was expected as the RD. Results: A total of 9 pts (3 at Level 0, 6 at Level 1) were included in Step 1. The baseline characteristics were as follows: the median age was 62 years; 6 were male; 6 presented with a left-sided tumor; 8 had a performance status of 0; all wild type/ RAS mutant/ BRAF V600E mutant were 8/1/0; and UGT1A1 wild type/*6 single hetero/*28 single hetero were 7/0/2. In Level 0 (IRI 200 mg/m2, OX 100 mg/m2), one grade 4 neutropenia and one grade 3 anorexia were observed, but without DLT. In Level 1 (IRI 200 mg/m2, OX 130 mg/m2), two grade 4 neutropenia and one grade 3 colitis were observed, with 1 DLT (febrile neutropenia) case, fully recovered without G-CSF administration. No treatment-related deaths were observed. Although dose modifications were needed in 4 of the 6 pts, no further safety concerns related to treatment continuity were observed in the 2nd or subsequent cycles. Thus, we determined that the dose administered in Level 1 is the RD for Step 2. According to the preliminary efficacy results at 8 weeks after initiating study treatment, 6 pts achieved a partial response (2 in Level 0 and 4 in Level 1). Conclusions: The RD of CAPOXIRI+BEV was 200 mg/m2 IRI, 130 mg/m2 OX, 1600 mg/m2 CAP, and 7.5mg/kg BEV. The randomized phase II Step (Step 2) of QUATTRO-II is ongoing. Clinical trial information: NCT04097444.

Initial experience of TAS-102 chemotherapy in Australian patients with chemorefractory metastatic colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 71-71
Author(s):  
Azim Jalali ◽  
Hui-Li Wong ◽  
Rachel Wong ◽  
Margaret Lee ◽  
Lucy Gately ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Febrile Neutropenia ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Performance Status ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Performance Status ◽  
Number Of Patients

71 Background: For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. In Australia, TAS-102 was initially made available locally through patients self-funding, later via an industry sponsored Medicine Access Program (MAP) and then via the Pharmaceutical Benefits Scheme (PBS). This study aims to investigate the efficacy and safety of TAS-102 in real world Australian population. Methods: A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to all TRACC patients and those enrolled in the registration study (RECOURSE). Results: Across 13 sites, 107 patients were treated with TAS-102 (non-PBS n = 27, PBS n = 80), The median number of patients per site was 7 (range: 1-17). The median age was 60 years (range: 31-83), compared to 67 for all TRACC patients and 63 for RECOURSE. Comparing registry TAS-102 and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 39% vs 49% were RAS wild type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median clinician assessed progression-free survival was 3.3 compared to RECIST defined PFS of 2 months in RECOURSE study, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths in the real-world series, where TAS102 dose at treatment initiation was at clinician discretion. In the RECOURSE study there was a 4% febrile neutropenia rate and one treatment-related death. Conclusions: TRACC registry patients treated with TAS102 were younger than both TRACC patients overall and those from the RECOURSE trial. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS. However overall survival outcomes achieved with TAS102 in real world patients were comparable to findings from this pivotal trial with an acceptable rate of major adverse events.

scholarly journals Treatments after Immune Checkpoint Inhibitors in Patients with dMMR/MSI Metastatic Colorectal Cancer

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 406
Author(s):  
Quang Loc Bui ◽  
Léo Mas ◽  
Antoine Hollebecque ◽  
David Tougeron ◽  
Christelle de la Fouchardière ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Immune Checkpoints ◽  
Repair Deficiency ◽  
Improved Outcomes ◽  
Number Of Patients ◽  
Tumor Types

Background: Several studies reported improved outcomes with conventional treatments (CT, i.e., chemotherapy ± targeted therapy) administered after immune checkpoints inhibitors (ICI) in certain tumor types. No data are available concerning patients (pts) with metastatic colorectal cancer (mCRC) harboring mismatch repair deficiency/microsatellite instability (dMMR/MSI). We aimed to assess the outcomes of dMMR/MSI mCRC pts receiving CT after ICI failure. Methods: We conducted a retrospective multicenter study investigating the outcomes of all dMMR/MSI mCRC pts who received post-ICI CT between 2015 and 2020. Results: 31 pts (male 61%, median age 56 years) were included. ICI was an anti-PD(L)1 monotherapy in 71% of pts, and 61% received >2 lines before post-ICI CT. The overall response rate and disease control rate were 13% and 45%, with a median progression-free survival (PFS) and overall survival of 2.9 and 7.4 months, respectively. No association of the outcomes with either ICI efficacy or anti-angiogenic agents was observed. Prolonged PFS (range 16.1–21.3 months) was observed in 4 pts (13%). Conclusions: Although conducted on a limited number of patients, our results do not support an association of previous ICI treatment with an enhanced efficacy of CT in dMMR/MSI mCRC. However, prolonged disease control was observed in several cases, suggesting that some pts might derive an unexpected benefit from post-ICI treatments.

Phase III Multicenter Randomized Trial of Oxaliplatin Added to Chronomodulated Fluorouracil–Leucovorin as First-Line Treatment of Metastatic Colorectal Cancer

2000 ◽  
Vol 18 (1) ◽  
pp. 136-136 ◽  
Author(s):  
S. Giacchetti ◽  
B. Perpoint ◽  
R. Zidani ◽  
N. Le Bail ◽  
R. Faggiuolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Phase Iii ◽  
Line Treatment ◽  
Survival Times ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)–leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m2/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m2, as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU–LV occurred in ≤ 5% of the patients (≤ 1% of the courses). Grade 3 to 4 diarrhea occurred in 43% of the patients given l-OHP (10% of the courses), and less than 2% of the patients had severe hematotoxicity. Thirteen percent of the patients had moderate functional impairment from peripheral sensory neuropathy. Sixteen percent of the patients receiving 5-FU–LV had an objective response (95% confidence interval [CI], 9% to 24%), compared with 53% of those receiving additional l-OHP (95% CI, 42% to 63%) (P < .001). The median progression-free survival time was 6.1 months with 5-FU–LV (range, 4.1 to 7.4 months) and 8.7 months (7.4 to 9.2 months) with l-OHP and 5-FU–LV (P = .048). Median survival times were 19.9 and 19.4 months, respectively. CONCLUSION: By chronomodulating 5-FU–LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.

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 ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Nutritional Status ◽  
Metastatic Colorectal Cancer ◽  
Multicenter Study ◽  
Cytotoxic Chemotherapy ◽  
Response To Treatment ◽  
Severe Malnutrition ◽  
Chemotherapy Response ◽  
Drug Induced

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.

scholarly journals Loss of Chromosome 18q11.2-q12.1 Is Predictive for Survival in Patients With Metastatic Colorectal Cancer Treated With Bevacizumab

2018 ◽  
Vol 36 (20) ◽  
pp. 2052-2060 ◽  
Author(s):  
Erik van Dijk ◽  
Hedde D. Biesma ◽  
Martijn Cordes ◽  
Dominiek Smeets ◽  
Maarten Neerincx ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Multicenter Study ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Tumor Biopsy ◽  
Overall Response ◽  
European Multicenter Study

Purpose Patients with metastatic colorectal cancer (mCRC) have limited benefit from the addition of bevacizumab to standard chemotherapy. However, a subset probably benefits substantially, highlighting an unmet clinical need for a biomarker of response to bevacizumab. Previously, we demonstrated that losses of chromosomes 5q34, 17q12, and 18q11.2-q12.1 had a significant correlation with progression-free survival (PFS) in patients with mCRC treated with bevacizumab in the CAIRO2 clinical trial but not in patients who did not receive bevacizumab in the CAIRO trial. This study was designed to validate these findings. Materials and Methods Primary mCRC samples were analyzed from two cohorts of patients who received bevacizumab as first-line treatment; 96 samples from the European multicenter study Angiopredict (APD) and 81 samples from the Italian multicenter study, MOMA. A third cohort of 90 samples from patients with mCRC who did not receive bevacizumab was analyzed. Copy number aberrations of tumor biopsy specimens were measured by shallow whole-genome sequencing and were correlated with PFS, overall survival (OS), and response. Results Loss of chromosome 18q11.2-q12.1 was associated with prolonged PFS most significantly in both the cohorts that received bevacizumab (APD: hazard ratio, 0.54; P = .01; PFS difference, 65 days; MOMA: hazard ratio, 0.55; P = .019; PFS difference, 49 days). A similar association was found for OS and overall response rate in these two cohorts, which became significant when combined with the CAIRO2 cohort. Median PFS in the cohort of patients with mCRC who did not receive bevacizumab and in the CAIRO cohort was similar to that of the APD, MOMA, and CAIRO2 patients without an 18q11.2-q12.1 loss. Conclusion We conclude that the loss of chromosome 18q11.2-q12.1 is consistently predictive for prolonged PFS in patients receiving bevacizumab. The predictive value of this loss is substantiated by a significant gain in OS and overall response rate.

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