Evolution of skeletal muscle mass (SMM) during palliative systemic treatment in metastatic colorectal cancer (mCRC) patients participating in the randomized phase 3 CAIRO3 study

Date

08 Oct 2016

Session

Poster Display

Presenters

Sophie Kurk

Citation

Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370

Authors

S.A. Kurk1, P.H.M. Peeters2, B. Dorresteijn3, M. Jourdan3, H.J. Kuijf4, C. Punt5, M. Koopman6, A.M. May7

Author affiliations

  • 1 Medical Oncology, University Medical Center Utrecht, 3508GA - Utrecht/NL
  • 2 Public Health, Imperial College London-South Kensington Campus, London/GB
  • 3 Oncology, Nutricia Research, Utrecht/NL
  • 4 Image Science Institute, University Medical Center Utrecht, Utrecht/NL
  • 5 Medical Oncology, Academic Medical Center, University of Amsterdam, 1100 DD - Amsterdam/NL
  • 6 Medical Oncology, University Medical Center Utrecht, 3584 CX - Utrecht/NL
  • 7 Julius Center For Health Sciences And Primary Care, University Medical Center Utrecht, Utrecht/NL
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Background

Observational studies suggest that low SMM is associated with chemotherapy-related toxicity and poor survival in mCRC patients. Little is known about patterns of SMM during palliative systemic therapy. Here we use data of the CAIRO3 study (Simkens et al. Lancet 2015) in which mCRC patients with stable disease or better after 6 cycles capecitabine + oxaliplatin + bevacizumab (CAPOX-B) were randomized between maintenance treatment with capecitabine + bevacizumab (CAP-B, M) and observation (O). In both groups CAPOX-B or other treatment was reintroduced upon disease progression until second disease progression, which was also the primary study endpoint. We used repeated scan data of 101 CAIRO3 patients to investigate SMM during treatment.

Methods

307 CT-scans of 101 randomly chosen CAIRO3 patients (63.1 ± 9.0 years, M n = 51; O n = 50) were analyzed for SMM at four time points (i.e. prior to start pre-randomization induction treatment, at randomization, at first and at second disease progression) using single slice evaluation at L3. A linear mixed effects model was used to assess SMM changes both within and between study arms.

Results

Before CAIRO3 randomization during 6 cycles of CAPOX-B induction treatment, SMM decreased significantly in all patients (M: -0.8kg, (95% CI -0,14; -1,2) and O: -0,7kg (-0,4; -1,6)). After randomization, SMM recovered during maintenance treatment by 0,2kg (-0.3; 0,8) and observation -0.5kg (-1,1; 0,2) both compared to pre-induction SMM levels (median time 9.0 months and 4.3 months for M and O, respectively). After first progression and during reinduction treatment with CAPOX-B or other treatment, SMM again decreased significantly and similarly in both arms, M: -0,9kg (-0,1; -1.6), and O: -1,5kg (-0,8; -2,3) compared to pre-induction SMM levels (median time from first progression until second progression M: 4,7 months and O: 6,1 months).

Conclusions

Our data shows that muscle loss in mCRC patients during palliative systemic therapy is reversible and varies with treatment regimen. Although studies have shown prognostic capacity for SMM, the effect of subsequent changes in SMM are unknown and may be clues for new future therapeutic interventions.

Clinical trial identification

ClinicalTrials.gov NCT00442637

Legal entity responsible for the study

Sophie Kurk

Funding

University Medical Center Utrecht

Disclosure

B. Dorresteijn, M. Jourdan: Employee of Nutricia Research. C. Punt: Advisory role: Roche, Amgen, Bayer, Nordic Pharma, Merck-Serono. M. Koopman: Advisory role: Amgen, Roche, Bayer, Merck. Research funding: Roche, Merck, Bayer. All other authors have declared no conflicts of interest.

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