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No evidence for changes in skeletal muscle mass or weight during first-line chemotherapy for metastatic colorectal cancer.

ABSTRACT: BACKGROUND:Studies over the past 10?years strongly support an association between skeletal muscle mass (SMM) depletion and outcome in metastatic colorectal cancer (mCRC). Factors influencing SMM changes over time are, however, poorly studied. We analyzed the impact of SMM on overall survival and chemotherapy toxicities in mCRC patients treated with first-line chemotherapy. Changes in weight and body composition were evaluated during follow-up. METHODS:Patients enrolled in the randomized phase II ACCORD trial comparing two chemotherapy regimens were screened. Body composition parameters (SMM, adipose tissue) were assessed prospectively with computed tomography (CT) imaging, and toxicities were recorded. Mixed models were used to assess weight and BC changes during 4?months of treatment follow-up. RESULTS:Among 145 patients included in ACCORD, 76 had available baseline CT scans and were included in the current study. Mean age was 60.6?±?10.0?years, 50% were women, 82% had colon cancer, and 62% had two or more metastatic sites. At baseline, 49% had lost at least 5% of their initial weight, including 26% who had lost more than 10%; 53% had SMM depletion. In this homogenous cohort, there were no statistically significant associations between SMM depletion and overall survival, progression-free survival or chemotherapy toxicity. There were no decreases in weight or SMM during follow-up. Weight and SMM changes were not influenced by diarrhea either grade 3-4 or any grade (reported in 74% of patients). For patients with weight loss ?10% at baseline, SMM increased significantly after 4?months of follow-up and after disease stabilization following chemotherapy (P?=?0.008). CONCLUSIONS:In a homogenous mCRC cohort, SMM depletion was not associated with survival or chemotherapy toxicity. Despite most patient experiencing diarrhea, no changes in weight or SMM were found during 4?months of follow-up. However, hypotheses deriving from our exploratory study have to be tested in further larger sample size studies. TRIAL REGISTRATION:Clinicaltrials.gov NCT00423696 (2011).

SUBMITTER: Antoun S

PROVIDER: S-EPMC6714393 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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No evidence for changes in skeletal muscle mass or weight during first-line chemotherapy for metastatic colorectal cancer.

Antoun Sami S Bayar Mohamed Amine MA Dyevre Valérie V Lanoy Emilie E Smolenschi Cristina C Ducreux Michel M

BMC cancer 20190828 1

<h4>Background</h4>Studies over the past 10 years strongly support an association between skeletal muscle mass (SMM) depletion and outcome in metastatic colorectal cancer (mCRC). Factors influencing SMM changes over time are, however, poorly studied. We analyzed the impact of SMM on overall survival and chemotherapy toxicities in mCRC patients treated with first-line chemotherapy. Changes in weight and body composition were evaluated during follow-up.<h4>Methods</h4>Patients enrolled in the rand ...[more]

PMID: 31462288

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Project description:BackgroundIncreasing evidence suggests that severe skeletal muscle index (SMI) loss (sarcopenia) is associated with poor overall survival in metastatic colorectal cancer patients, but its mechanisms are unknown. We recently found, using data of the randomized phase 3 CAIRO3 study, that SMI loss was related with shorter time to disease progression and overall survival during first-line maintenance treatment with capecitabine + bevacizumab (CAP-B) or observation and during more intensive capecitabine + oxaliplatin + bevacizumab (CAPOX-B) reintroduction treatment. As a potential risk factor for reduced survival, we explored whether sarcopenia and SMI loss were associated with dose-limiting toxicities (DLTs) during CAP-B and CAPOX-B.MethodsSarcopenia status and SMI loss were assessed by using consecutive computed tomography scans. DLTs were defined as any dose delay/reduction/discontinuation of systemic treatment because of reported CTCAE (version 3.0) toxicities at the start or during treatment. Poisson regression models were used to study whether sarcopenia and body mass index (BMI) at the start of treatment and SMI and BMI loss during treatment were associated with DLTs.ResultsOne hundred eighty-two patients (mean age 63.0 ± 8.8 years, 37% female) received CAP-B, and 232 patients (mean age 63.0 ± 9.0 years, 34% female) received CAPOX-B. At the start of CAP-B and CAPOX-B, 54% and 46% of patients were sarcopenic, respectively. Mean BMI was lower in sarcopenic patients, although patients were on average still overweight (sarcopenic vs. non-sarcopenic at the start of CAP-B 25.0 ± 3.9 vs. 26.7 ± 4.1 and CAPOX-B 25.8 ± 3.8 vs. 27.1 ± 3.8 kg/m2 ). Sarcopenia at the start of CAP-B was not associated with DLTs [relative risk 0.87 (95% confidence interval 0.64-1.19)], whereas patients with >2% SMI loss had a significantly higher risk of DLTs [1.29 (1.01-1.66)]. At the start of subsequent CAPOX-B, 25% of patients received a dose reduction, and the risk of dose reduction was significantly higher for patients with preceding SMI loss [1.78 (1.06-3.01)] or sarcopenia [1.75 (1.08-2.86)]. After the received dose reductions, sarcopenia or SMI loss was not significantly associated with a higher risk of DLTs during CAPOX-B [sarcopenia vs. non-sarcopenic: 0.86 (0.69-1.08) and SMI loss vs. stable/gain: 0.83 (0.65-1.07)]. In contrast, BMI (loss) at the start or during either treatment was not associated with an increased risk of DLTs.ConclusionsIn this large longitudinal study in metastatic colorectal cancer patients during palliative systemic treatment, sarcopenia and/or muscle loss was associated with an increased risk of DLTs. BMI was not associated with DLTs and could not detect sarcopenia or SMI loss. Prospective (randomized) studies should reveal whether normalizing chemotherapeutic doses to muscle mass or muscle mass preservation (by exercise and nutritional interventions) increases chemotherapeutic tolerance and improves survival.

Project description:BackgroundObservational studies suggest that loss of skeletal muscle mass (SMM) is associated with chemotherapy-related toxicity, poor quality of life, and poor survival in metastatic colorectal cancer (mCRC) patients. Little is known about the evolution of SMM during palliative systemic therapy. We investigated changes in SMM during various consecutive palliative systemic treatment regimens using repeated abdominal computed tomography scans of mCRC patients who participated in the randomized phase 3 CAIRO3 study.MethodsIn the CAIRO3 study, mCRC patients with stable disease or better after 6 cycles of first-line treatment with capecitabine + oxaliplatin + bevacizumab (CAPOX-B) were randomized between maintenance treatment with capecitabine + bevacizumab (CAP-B) or observation. Upon first disease progression, in both groups, CAPOX-B or other treatment was reintroduced until the second disease progression, which was the primary study endpoint. We analysed 1355 computed tomography scans of 450 (81%) CAIRO3 patients (64 ± 9.0 years, CAP-B n = 223; observation n = 227) for SMM at four time points (i.e. prior to the start of pre-randomization initial treatment, at randomization, and at first and at second disease progression) using the Slice-o-matic software and single slice evaluation at the lumbar 3 level. By using accepted and widely used formulas, whole body SMM was calculated. A linear mixed effects model, adjusted for relevant confounders, was used to assess SMM changes for the total group and within and between study arms.ResultsDuring 6 cycles of initial treatment with CAPOX-B prior to randomization, SMM decreased significantly in all patients [CAP-B arm: -0.53 kg (95% CI -1.12; -0.07) and observation arm: -0.85 kg (-1.45; -0.25)]. After randomization, SMM recovered during CAP-B treatment by 1.32 kg (0.73; 1.90) and observation by 1.20 kg (0.63; 1.78) (median time from randomization to first disease progression 8.6 and 4.1 months for CAP-B arm and observation arm, respectively). After first progression and during reintroduction treatment with CAPOX-B or other treatment, SMM again decreased significantly and comparable in both arms, CAP-B: -2.71 kg (-3.37; -2.03), and observation: -2.01 kg (-2.64; -1.41) (median time from first progression until second progression CAP-B arm: 4.7 months and observation arm: 6.6 months).ConclusionsThis longitudinal study provides a unique insight in SMM changes in mCRC patients during palliative systemic treatment regimens, including observation. Our data show that muscle loss is reversible and may be influenced by the intensity of systemic regimens. Although studies have shown prognostic capacity for SMM, the effects of subsequent changes in SMM are unknown and may be clues for new future therapeutic interventions.

Dataset Information

No evidence for changes in skeletal muscle mass or weight during first-line chemotherapy for metastatic colorectal cancer.

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No evidence for changes in skeletal muscle mass or weight during first-line chemotherapy for metastatic colorectal cancer.

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