Incidence, evolution and risk factors of hypophosphatemia in patients with solid tumors receiving ferric carboxymaltose: a retrospective cohort study

ABSTRACT

Objectives

Ferric carboxymaltose (FCM) is increasingly used in the management of cancer-related anemia, yet it may cause hypophosphatemia. This retrospective study describes the incidence, evolution and risk factors of hypophosphatemia in a cohort of patients with solid tumors receiving FCM.

Methods

Serum phosphorus concentration was assessed longitudinally using a random intercepts model. The probability of developing hypophosphatemia, as graded by CTCAE version 4.0, was investigated using a multi-state model. Transition hazards were modeled non-parametrically and semi-parametrically by a Cox model. Causal marginal risk differences between baseline interventions on serum phosphorus and/or FCM dose were obtained via G-computation.

Results

In 174 ambulatory patients with solid tumors receiving FCM at two university hospitals between October 2020 and September 2021, the risk of developing moderate-to-severe hypophosphatemia was 36.0% (95% confidence interval (CI) 28.2–43.9%) and peaked within 16 days after first FCM administration. The average duration of moderate-to-severe hypophosphatemia was 12.4 days. After adjustment for confounders, lower baseline serum phosphorus (adjusted hazard ratio (aHR) 0.88 per 0.1 mmol/L increase, 95% CI 0.79–0.98) and higher FCM dose (first dose: aHR 1.12 per 1 mg/kg increase, 95% CI 1.01–1.25; second dose: aHR 1.06 per 1 mg/kg increase, 95% CI 1.00–1.13) significantly increased the hazard of moderate-to-severe hypophosphatemia.

Conclusion

Approximately one out of three ambulatory patients with solid tumors may develop moderate-to-severe hypophosphatemia after FCM administration. Baseline serum phosphorus and FCM dose may be modifiable risk factors that should be considered for intervention in order to mitigate the risk of hypophosphatemia.

KEYWORDS:

• Anemia
• cancer
• ferric carboxymaltose
• iron deficiency
• intravenous iron
• hypophosphatemia

Disclosure statement

The authors have no relevant financial or non-financial interests to disclose.

Authors’ contribution

AD, KK, SD, SR, HD and LL contributed to the study conception. AD and KK applied for the ethics approval and collected the data. AD performed the statistical analysis and drafted the manuscript. KK, SD, SR, HD and LL were involved in the data interpretation and critically revised the draft versions of the manuscript. All authors read and approved the final manuscript.

Ethics approval

This study was approved by the local ethics committees of Ghent University Hospital (project number BC-11548) and University Hospital Brussels (project number EC-2022-129).

Consent to participate

The need for informed consent was waived by the local ethics committees due to the retrospective nature of this study.

Data availability

The dataset generated during and analyzed during the current study is available from the corresponding author on reasonable request.

Code availability

The code used during the current study is available from the corresponding author on reasonable request.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17843286.2022.2153465

Additional information

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.