The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, ...leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI).
Selection criteria included unresectable metastatic colorectal cancer, age 18 to 75 years, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR).
A total of 244 patients were randomly assigned. An increase of grade 2 to 3 peripheral neurotoxicity (0% v 19%; P < .001), and grade 3 to 4 neutropenia (28% v 50%; P < .001) were observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3% v 5%) and grade 3 to 4 diarrhea (12% v 20%) were not significantly different. Responses, as assessed by investigators, were, for FOLFIRI and FOLFOXIRI, respectively, complete, 6% and 8%; and partial, 35% and 58%, (RR, 41% v 66%; P = .0002). RR confirmed by an external panel was 34% versus 60% (P < .0001). The R0 secondary resection rate of metastases was greater in the FOLFOXIRI arm (6% v 15%; P = .033, among all 244 patients; and 12% v 36%; P = .017 among patients with liver metastases only). Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 v 9.8 months; hazard ratio HR, 0.63; P = .0006; median OS, 16.7 v 22.6 months; HR, 0.70; P = .032).
The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer with favorable prognostic characteristics. Further studies of FOLFOXIRI in combination with targeted agents and in the neoadjuvant setting are warranted.
Response shift (RS) has been defined as a change in the meaning of an individual's self-evaluation that needs to be accounted for when assessing longitudinal changes in health-related quality of life ...(HRQoL). RS detection through structural equation modeling is accomplished by adopting Oort's procedure based on a measurement model in which the observed variables are defined as reflective indicators of the HRQoL latent variable; that is, the latent variable causes the variation in the reflective indicators. This study aims to propose a procedure that assesses RS when formative indicators are used in measuring HRQoL; in this last case, the latent variable is considered to be a function of some formative indicators. A secondary aim is to compare the new procedure with Oort's procedure to highlight similarities and differences.
The data were retrieved from a consecutive series of 258 patients newly diagnosed with colorectal cancer and undergoing chemotherapy and/or surgery. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QOL-C30) was administered twice, once before and once six months after treatment. Structural equation modeling was used to evaluate RS and true change with the newly proposed method (in which fatigue and pain were defined as formative indicators) and with Oort's procedure (in which fatigue and pain were defined as reflective indicators).
According to the new procedure, there was no measurement bias, and on average, patients' quality of life improved by 3.53 points (on a scale ranging from 0 to 100) at the 6-month follow-up. With Oort's procedure, the loading of the pain indicator was not invariant across the two time points, suggesting the presence of reprioritization, whereas the estimation of true change was very similar to the previous one: 3.87.
RS and true change in HRQoL can be evaluated in the presence of formative indicators. Defining a measurement model by formative or reflective indicators can lead to different results.
Relationships between loss of functioning, symptom burden, supportive care needs, and quality of life (QoL) have been suggested in cancer populations. This cross-sectional study further investigates ...these relationships through mediation analyses.
A total of 276 advanced colorectal cancer (CRC) patients completed validated instruments to assess cancer-related functioning, symptoms, supportive care needs, and QoL. Pearson's correlations and multiple mediation models with bootstrapping method were performed.
QoL had negative correlations with supportive care needs, positive correlations with functioning measures, and negative correlations with symptom scales. Supportive care needs had negative correlations with functioning measures and positive correlations with symptom scales. Mediation analyses showed significant indirect effects of CRC-related functioning and symptoms on QoL through supportive care needs.
Significant links between CRC-related loss of functioning, symptom burden, QoL, and supportive care needs have been established. Longitudinal studies are planned to clarify cause-and-effects relationships and establish sequences of events.
Objectives: The aim of this study was to conduct a discrete choice experiment with patients affected by colorectal cancer to understand their preferences for different attributes of the chemotherapy ...supply. Our overall goal is to provide evidence on the relative importance of each attribute in order to tailor chemotherapy supply according to patients' priorities in the design or reorganization processes of cancer services.
Methods: Focus groups were used to identify the attributes and levels for the discrete choice experiment. The attributes were: continuity of care, understanding, information, treatment choice, and time for therapy. Respondents were asked to choose between two mutually exclusive hypothetical alternatives of chemotherapy supply. Patients completed the discrete choice experiment along with the health-related quality of life and patients' satisfaction questions. Conditional and mixed logistic models were used to analyses the data.
Results: Patients with colorectal cancer treated with chemotherapy (n = 76) completed the survey. The most important aspects of chemotherapy supply were: "Providing detailed and complete information" and "High ability in understanding" patients. Preferences were also influenced by the availability of a trusted doctor. Except for one attribute (waiting time for therapy), all other characteristics significantly influenced respondents' preferences.
Conclusions: Results should support a policy of strengthening medical doctors' capabilities to communicate with patients, providing them complete information and involving them in the clinical decisions. Specifically, the findings should be used to improve the current provision of cancer care by identifying areas of preferred intervention from the perspectives of patients in order to tailor the service supply accordingly.
In mCRC, CEA is used to monitor response to systemic therapy together with imaging. After the end of induction, no major improvement in tumour shrinkage is expected, and the availability of a marker ...able to predict progressive disease (PD) versus no-PD might allow avoiding CT scans.
We pooled data from patients with baseline CEA ≥ 10 ng/mL included in TRIBE and TRIBE2 studies with the aim of identifying a threshold for percent increase of CEA from nadir able to predict PD after the end of the induction therapy.
In total, 1178 paired CEA and radiological assessments from 434 patients were included. According to the optimal cut-off determined by ROC, a CEA increase of at least 120% from nadir differentiated between PD and no-PD with a sensitivity of 74% and a specificity of 78%, excluding PD in the 92% of radiological assessments and allowing to avoid the 67% of CT scans. However, CEA cut-off of 120% was not able to detect radiological PD in 26% of cases. In order to mitigate this issue, a different clinically relevant threshold was evaluated based on the best sensitivity cut-off. Therefore, using any CEA increase from nadir as a threshold, the sensitivity grew to 93% and only in the 7% of cases the radiological PD was not detected.
In mCRC with baseline CEA ≥ 10 ng/mL, CEA values can accurately predict PD versus no-PD after the end of the first-line induction therapy.
Anti‐EGFRs plus doublet chemotherapy is considered the optimal upfront option for RAS/BRAF wild‐type left‐sided metastatic colorectal cancer (mCRC). Early‐onset (EO) mCRC has an increasing incidence ...and its prognostic/predictive role and management is debatable. We performed a post hoc analysis of Valentino study, that randomized RAS wild‐type mCRC patients to two panitumumab‐based maintenance regimens after FOLFOX/panitumumab induction. We assessed the safety and efficacy outcomes in patients stratified for age (<50/≥50 years old). We assessed progression‐free survival (PFS), overall survival (OS), response rate (ORR), rate of treatment‐related and panitumumab‐related adverse events (AEs) and quality of life (QoL). In 229 patients enrolled, 35 (15%) had EO mCRC, with a higher rate of female sex (P = .020) and lower rate of primary tumor resection (P = .001). Median PFS and OS were 10.9 vs 10.8 months (P = .593) and 28.1 vs 27.5 months (P = .865) in patients <50 and ≥50 years old, respectively, with no significant impact of maintenance arm. ORR and disease control rate were 74% vs 65% (P = .337) and 97% vs 81% (P = .013) in patients <50 or ≥50 years old. In younger patients, a trend for increased chemotherapy‐related AEs (peculiarly anemia) was shown, while significantly decreased EGFR‐related hypomagnesemia and increased skin rash were reported. No significant differences in treatment intensity or QoL were observed. In patients with EO mCRC and RAS wild‐type status, we found no differences in terms of survival outcomes based on age when selecting maintenance strategies. Management of treatment‐related AEs should consider the differential toxicity profile of age and sex.
What's new?
In patients with RAS and BRAF wild‐type metastatic colorectal cancer (mCRC), doublet chemotherapy with antiepidermal growth factor receptor (anti‐EGFR) agents is a recommended upfront regimen. However, data on the influence of younger age on the efficacy and safety outcomes of an EGFR‐based first‐line treatment strategy remain scant. In this post hoc analysis of the Valentino study, the authors report no significant differences in survival outcomes between patients <50 and ≥50 years old but reveal a differential toxicity profile. Rather than an intensification/modulation of the therapeutic schedule, the results support a differential toxicity management/prevention approach according to age and sex.
Introduction
The antiangiogenic monoclonal antibody aflibercept in association with fluorouracil and irinotecan improves the survival of patients with metastatic colorectal cancer (mCRC) treated ...previously with oxaliplatin-based therapy. Multiple reports raised the hypothesis that the concomitant use of antiresorptive drugs and antiangiogenic drugs may increase the risk of osteonecrosis of the jaw (ONJ). Some reports have been published regarding cases of ONJ during treatment with bevacizumab for mCRC.
Case description
Here we describe the first reported case of ONJ occurring in a 64-year-old woman with untreated periodontitis and episodic previous pyorrhea occurring during treatment with aflibercept plus FOLFIRI during the expanded-access program.
Conclusions
This case report warrants further investigation into the potential association between the use of anti-VEGF agents and ONJ. Given the serious nature of ONJ, we recommend that particular attention be paid to the oral district prior to treating patients and during treatment with chemotherapy and targeted agents, especially anti-VEGF agents. Such measures could also be useful in reducing the incidence of stomatitis.
Obesity is associated with an increased risk of development and recurrence of colorectal cancer. The role of obesity in metastatic colorectal cancer patients (pts) is still unclear, especially in ...those treated with triplet plus bevacizumab (bev). The aim of our study was to evaluate the prognostic and predictive role of BMI in metastatic colorectal cancer pts treated with FOLFOXIRI plus bev or FOLFIRI/FOLFOX plus bev in the TRIBE and TRIBE-2 trial.
A total of 1160 pts enrolled in TRIBE and TRIBE-2 trials were included. Baseline height and weight were used to assign pts to one of the following BMI categories: underweight (group A = BMI <18.5 kg/m2; 52 pts), normal (group B = BMI 18.5-29.9 kg/m2; 952 pts) and obese (group C > 30 kg/m2; 156 pts).
In our population, no differences in terms of PFS (P = .43) or OS (P = .99) resulted between 3 groups. No interaction effect between treatment arm and BMI was evident in terms of PFS (Group A HR: 0.65 95%CI: 0.36-1.16; Group B HR: 0.77 95%CI: 0.67-0.88; Group C HR: 0.67 95%CI: 0.48-0.93; P for interaction = .75) or OS (Group A HR: 0.57 95%CI: 0.29-1.12; Group B HR: 0.85 95%CI: 0.73-0.99;Group C HR: 0.69 95%CI: 0.48-1.01 P for interaction = .36). No statistically significant difference in terms of dose reductions due to toxicities were found according to BMI in the overall population (P = .48) and in pts treated with FOLFOXIRI plus bev (P = .57).
BMI was neither prognostic or predictive for PFS and OS in our population. Our analyses showed that the advantage of FOLFOXIRI plus bev versus FOLFIRI/FOLFOX plus bev was independent from BMI.
The role of body mass index is unclear in metastatic colorectal cancer patients. We analyzed data from 1160 pts enrolled in TRIBE and TRIBE-2 trials. Our analyses showed that BMI was neither prognostic nor predictive for PFS and OS.
Micro-Abstract No effective preventive strategies for cetuximab-induced skin rash are available. In a homogeneous population of 41 consecutive patients with metastatic colorectal cancer, the ...preventive application of vitamin K1 –based cream reduced the development of moderate-to-severe skin rash.
Neo-adjuvant chemo-radiotherapy (CT–RT) has been shown to decrease local recurrence rate in locally advanced rectal cancer. This multicenter phase II trial was conducted to evaluate the feasibility, ...safety and effectiveness of a combination of pre-operative radiotherapy and concurrent Capecitabine plus Oxaliplatin (XELOXART Trial). From October 2008 to May 2011, fifty consecutive patients affected with T3/T4 and/or N+ rectal cancer were enrolled. Treatment protocol consisted of 50.4 Gy in 28 fractions, Oxaliplatin 60 mg/m
2
once a week for 6 weeks and oral Capecitabine 825 mg/m
2
twice daily from day 1 to 14 and from day 22 to 35. Surgery was planned 6–8 weeks after. Main endpoints were pathological complete response rate (pCR) and the type of surgery performed compared to the planned one at diagnosis. 50 patients were included; pCR (ypT0N0M0) was achieved in 6 patients (12 %). Tumour downstaging was observed in 27 patients (54 %), and nodal downstaging in 32 patients (64 %). A total of 32 patients had lower rectal cancer, with 24 candidate for abdominal-perineal resection. At the end of CT–RT, a total of 12/24 (50 %) underwent conservative surgery. Grade 3 toxicity (fatigue and diarrhoea) occurred in 4 % of patients; grade 4 sensory neuropathy occurred in 2 % of patients. Perioperative complications of any grade occurred in 10 % of patients. Pre-operative CT–RT with Capecitabine-Oxaliplatin was well tolerated and resulted in an encouraging sphincter preservation and tumour downstaging rate. No improvements in terms of pathological complete response rate were shown.
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