Muscle mass at the time of diagnosis of nonmetastatic colon cancer and early discontinuation of chemotherapy, delays, and dose reductions on adjuvant FOLFOX: The C-SCANS study

Abstract

Background: For many chemotherapy regimens dosed based on body surface area (BSA), patients experience dose reductions or delays or discontinue treatment, thereby reducing survival. Consideration of body composition may be useful in individualizing chemotherapy dosing, but to the authors' knowledge few studies to date have examined the association of body composition with chemotherapy tolerance in patients with colon cancer.

Methods: The authors identified patients with nonmetastatic colon cancer who were diagnosed from 2006 through 2011 at Kaiser Permanente and who received leucovorin calcium/calcium folinate, 5-fluorouracil, and oxaliplatin (FOLFOX) as initial adjuvant chemotherapy (533 patients). Patients' muscle mass was quantified using clinically acquired computed tomography scans. The authors quantified chemotherapy doses, treatment dates, and related toxicities using the electronic medical record. In logistic regression models adjusting for age, sex, and American Joint Committee on Cancer stage of disease, the authors examined associations of muscle tertiles with early treatment discontinuation (<6 cycles), treatment delay (>3 days off schedule for ≥3 times), and/or dose reduction (relative dose intensity ≤ 0.70, based on planned treatment).

Results: The average age of the patients at the time of diagnosis was 58.7 years; BSA was 1.9 m² and body mass index was 28.7 kg/m² . Compared with the highest sex-specific tertile of muscle mass, patients in the lowest tertile were more likely to experience toxicities and had twice the risk of adverse outcomes while receiving FOLFOX; for early discontinuation, the odds ratio (OR) was 2.34 (95% confidence interval [95% CI], 1.04-5.24; P for trend = .03), whereas the ORs were 2.24 (95% CI, 1.37-3.66; P for trend = .002) for treatment delay and 2.28 (95% CI, 1.19-4.36; P for trend = .01) for dose reduction.

Conclusions: Lower muscle mass is associated with greater toxicity and poor chemotherapy adherence among patients receiving FOLFOX. Many chemotherapy drugs are dosed based on BSA, but treatment may be better individualized if muscle mass is considered. Cancer 2017;123:4868-77. © 2017 American Cancer Society.

Keywords: body composition; body surface area; chemotherapy; colon cancer; dose-limiting toxicity; relative dose intensity; skeletal muscle mass.

Figure 1

Variation in Body Composition Among Colon Cancer Patients with Similar Body Surface Area Clinically-acquired axial computed tomography images with muscle areas contoured at the third lumbar vertebra from two male colon cancer patients with similar body mass index (30-kg/m²) and BSA (2.0), but different muscle areas (Patient A: 207 cm²; Patient B: 104 cm²).

Figure 2

Survival Probability by Early Discontinuation of FOLFOX (n=533) Black Kaplan-Meier curves indicate the survival probabilities for patients who discontinued treatment with <6 cycles of FOLFOX, while gray Kaplan-Meier curves indicate patients who received ≥6 cycles of FOLFOX

Figure 3

Odds Ratios for Adverse Outcomes on FOLFOX: Patients in the Lowest versus Highest Tertile of Muscle Mass (n=533) Each symbol on the plot represents a separate odds ratio estimate comparing the lowest to the highest tertile of muscle mass from logistic regression models adjust for age at diagnosis in years, cancer stage and sex.