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CNS tumours

4943 - Early platelet variation during concomitant chemo-radiotherapy predicts adjuvant temozolomide-induced thrombocytopenia in newly-diagnosed glioblastoma

Date

09 Sep 2017

Session

CNS tumours

Topics

Cytotoxic Therapy;  Supportive Care and Symptom Management;  Central Nervous System Malignancies

Presenters

Maxime Fontanilles

Citation

Annals of Oncology (2017) 28 (suppl_5): v109-v121. 10.1093/annonc/mdx366

Authors

M. Fontanilles1, F. Clatot2, C. Alexandru3, O. Langlois4, O. Veresezan5, F. Marguet6, M. David7, A. Laquerriere8, C. Hanzen9, I. Tennevet Bouilly10, F. Di Fiore11

Author affiliations

  • 1 Medical Oncology, Centre Henri Becquerel, 76038 - Rouen/FR
  • 2 Inserm U1245 Équipe De Recherche En Oncologie Normande Iron, Cancer Centre Henri Becquerel, 76000 - ROUEN/FR
  • 3 Medical Oncology, Cancer Centre Henri Becquerel, 76000 - ROUEN/FR
  • 4 Neurosurgery, Hopital Charles Nicolle, CHU Hopitaux de Rouen, 76000 - Rouen/FR
  • 5 Radiation Oncology And Medical Physics, Cancer Centre Henri Becquerel, 76000 - Rouen/FR
  • 6 Pathology, Hopital Charles Nicolle, CHU Hopitaux de Rouen, 76000 - Rouen/FR
  • 7 Biopathology, Cancer Centre Henri Becquerel, 76000 - ROUEN/FR
  • 8 Pathology, Hopital Charles Nicolle, CHU Hopitaux de Rouen, 76000 - ROUEN/FR
  • 9 Radiation Oncology And Medical Physics, Centre Henri Becquerel, 76038 - Rouen/FR
  • 10 Medical Oncology, Cancer Centre Henri Becquerel, 76038 - Rouen/FR
  • 11 Medical Oncology, Cancer Center Henri Becquerel, 76000 - ROUEN/FR
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Resources

Abstract 4943

Background

Although temozolomide (TMZ) was known to induce thrombocytopenia with subsequent cycle delay, dose reduction and early treatment discontinuation in glioblastoma multiforme (GBM), no early predictive test of these side effects has been yet clearly established. In this context, our aim was to identify the best threshold of early platelet variation predicting TMZ-induced thrombocytopenia during the TMZ maintenance phase and to validate it in an independent series of GBM patients.

Methods

It was a retrospective trial including patients suffering from newly diagnosed GBM and treated with TMZ at 75 mg/m2/day concomitant to radiotherapy (RT) followed by TMZ maintenance, according to the Stupp protocol. In a training set, variations of platelet concentrations occurring from the first week to week 6 (ΔW6) were analyzed to identify the most relevant platelet decrease during RT-TMZ associated with at least one clinically relevant TMZ-induced thrombocytopenia (≤100 G/l) in the maintenance phase. An independent validation cohort was used to validate the performance of the ΔW6 threshold.

Results

A total of 147 patients were included: 85 in the training set and 62 in the validation cohort. Twenty seven patients (18%) experienced at least one TMZ-induced thrombocytopenia in the maintenance phase, respectively 14 (16%) and 13 patients (21%) in each cohort; and was the most frequent cause of TMZ schedule changes (49%, 30/61). A platelet decrease at W6 ≥35% (ΔW6≥35%) was identified as the best predictive variation of clinically induced thrombocytopenia with an AUC of 0.83, a sensitivity (Se) of 65% and a specificity (Sp) of 96%. In the validation set, a presence of a ΔW6≥35% of platelet variation was associated with: Se 77% [95% CI 66%-87%], Sp 73% [62%-84%], positive predictive value 42% [29%-54%] and negative predictive value 92% [86%-99%].

Conclusions

Our results showed that a platelet decrease at W6 ≥35% during the RT-TMZ phase may be an early, widely faisable and costless marker of clinically relevant TMZ-induded thrombocyponia during the TMZ maintenance. Prospective studies are needed to evaluate the usefulness of this test for early TMZ schedule adaptation.

Clinical trial identification

Legal entity responsible for the study

Cancer Center Henri Becquerel

Funding

Cancer Center Henri Becquerel and IRIB

Disclosure

All authors have declared no conflicts of interest.

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