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The pharmacokinetics of methotrexate with and without rituximab in the treatment of primary central nervous system lymphoma (PCNSL)

Date

09 Oct 2016

Session

Poster display

Presenters

Fiona Rawat

Citation

Annals of Oncology (2016) 27 (6): 103-113. 10.1093/annonc/mdw367

Authors

F.R. Rawat1, A. Nolan2, S.Y. Teo2, M. Triggs3, G. Carroll3, S. Picardo4, V. Mallett4, N.M. Keegan4, I. Ismail4, B. Hennessy4, W. Grogan4, O. Breathnach4, P. Morris4

Author affiliations

  • 1 Department Of Medical Oncology, Royal College of Surgeons in Ireland, 2 - Dublin/IE
  • 2 Department Of Medical Oncology, Royal College of Surgeons in Ireland, Dublin/IE
  • 3 Department Of Pharmacy And Cancer Clinical Trials And Research Unit, Beaumont Hospital, Dublin/IE
  • 4 Cancer Clinical Trials And Research Unit, Beaumont Hospital, Dublin/IE
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Background

PCNSL is a rare B-cell lymphoma. Most chemotherapy regimens are methotrexate (MTX) - based, but recently have included Rituximab (R). MTX pharmacokinetics (PKs) are highly variable and may correlate with patient (pt) outcome. However, the effect of R on MTX PKs has not been well characterised. We aimed to compare MTX PKs in pts treated with and without R.

Methods

We conducted a retrospective study of the PCNSL database at the National Neuro-Oncology Centre in Dublin, Irleland. Pts received MTX (3.5g/m2)/Procarbazine/Vincristine (MTX group), or MTX/Procarbazine/Vincristine + Rituximab (R-MTX). From written and electronic medical records, the following data were collected: pt demographics, creatinine clearance (CrCl), MTX dose and MTX levels.

Results

From 2010 to 2015, 24 pts (14 men, 10 women) with median age of 67 (range 20-76) were included. Baseline characteristics were similar between pts who received R-MTX (n = 10) and MTX (n = 14); median (range) age 62 (20-73) vs. 68 (41-76), weight 82.5kg (61-133) vs. 78.5 (52-92.3), CrCl 123.3mls/min (53.2-214.1) vs. 108.3 (46.5-227.5), total MTX dose g/m2 7.0 (1.7-7.7) vs. 6.35 (5.3-7.1). In cycle 1, MTX clearance appeared to be prolonged in the R-MTX group (Table 1). Of note, mean MTX levels at 48hrs appeared similar in pts who received R-MTX (0.388) vs MTX (0.376). However, at 144hrs mean MTX levels appeared higher in pts who received R-MTX (0.147) vs. MTX (0.09). This difference in MTX levels was not apparent in subsequent cycles, possibly due to the confounding effects of MTX dose reductions; escalation in folinic acid and changes in CrCl. Correlation of MTX PKs with survival is ongoing. Table 1: Mean MTX Level Over Time

Hours 48 72 96 120 144 168 192 216
R-MTX 0.388 ± 0.56 0.115 ± 0.15 0.132 ± 0.12 0.167 ± 0.09 0.147 ± 0.1 0.113 ± 0.08 0.145 ± 0.11 0.105 ± 0.08
MTX 0.376 ± 0.46 0.164 ± 0.25 0.126 ± 0.07 0.12 ± 0.07 0.09 ± 0.03 0.08 ± 0.03 0.06 ± 0 0.05 ± 0

Values = mean ± SD.

Conclusions

This retrospective study in this rare cancer suggests that R may prolong MTX clearance. This may have implications for optimum MTX dosing and prognosis.

Clinical trial identification

Legal entity responsible for the study

Cancer Clinical Trials and Research Unit, Beaumont Hospital, Dublin, Ireland.

Funding

Cancer Clinical Trials and Research Unit, Beaumont Hospital, Dublin, Ireland.

Disclosure

All authors have declared no conflicts of interest.

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