prevention of thrombocytopenia in glioblastoma patients

Conditions: Thrombocytopenia; Glioblastoma

Summary: chemotherapy used in the treatment of primitive tumors of the central nervous system has a particularly important platelet toxicity compared to chemotherapy used for treatment of other tumors. chemotherapy postponed for toxicity is often due to thrombocytopenia (tp). the tp and/or the other anomalies of coagulation, which can be spontaneous (rogers, 2004) or induced (gerber, 2006) can have dramatic consequences: * specifically neurological (intratumoral bleeding with particularly important neovascularization) with a functional aggravation and sometimes involvement of vital prognosis, * digestive (garcia-rodiguez, 2001) in patients receiving long term treatment with corticoids (potential gastric toxicity). the encouraging results from the eortc/ncic trial by stupp (median survival among patients with newly diagnosed glioblastoma is 14.6 months with an estimated 5-year survival of 9, 8%), has changed the standard of care of these patients (stupp et al., 2009). patients with newly diagnosed, histologically confirmed glioblastoma receive radiotherapy (2 gy given 5 days per week for 6 weeks, for a total of 60 gy) plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (tmz) (150 to 200 mg per square meter for 5 days during each 28-day cycle). the stupp regimen is currently the treatment of reference for glioblastoma and is used as a basis in various clinical studies with new agents. this study aims to evaluate romiplostim for the treatment of tp secondary to initial tmz chemotherapy of glioblastomas.


Eligibility criteria:
inclusion criteria: * histological proof of newly diagnosed glioblastoma, * age: 18 and older, * information to patient and signed consent form, * indication for a " stupp " protocol (cerebral focal radiotherapy and concomitant tmz followed by adjuvant tmz - 6 cycles), * patient with grade 3 or 4 tp during temozolomide chemotherapy, regardless of when the onset of tp was: after completion of concomitant rt/ct, before adjuvant ct or during adjuvant ct and only if a minimum of 2 cycles are still planned, * normal initial platelets count (\> 100 000/mm3) before the start of temozolomide during the rt/ct concomitant phase, * adequate haematological, renal, hepatic function at the time of inclusion visit, * ecog ps 0-2 (patients unable to walk because of a paralysis and who are up in a wheel chair will be considered as ambulatory for the evaluation of the ecog performance status), * life expectancy \> 2 months, * patients covered by the french health insurance system, * negative pregnancy test at the time of inclusion visit, * if required, effective contraception respecting criteria of cpmp/ich/286/95 (such as implants, injectables, combined oral contraceptives, some iuds, sexual abstinence or vasectomised partner). exclusion criteria: * concomitant radiotherapy (romiplostim will be started after the completion of the rt/ct concomitant phase), * other malignancies (prior hx malignancies), * any anterior systemic chemotherapy, * any known coagulation disease or known haematological disease even if resolved. known hypercoagulate state (e.g., factor v leiden, protein c defiency, protein s deficiency, pt 20201, antiphospholipid antibody syndrome...), * prior romiplostim exposure or prior exposure to other tpo mimetics, * history of thromboembolic disease \< 6 months. treatment with anticoagulant such as heparin or antivitamin k (lmwh as prophylactic treatment is authorized), * any other hemato-toxicity (anemia, neutropenia) requiring epo or gcsf, * other causes of temozolomide interruption (non haematological toxicities), * known hypersensitivity to any e-coli derived product, * participation to any other study during the last 30 days, * refusal to give written informed consent, * pregnancy or nursing, * for all men and women of childbearing potential: refusal or inability to use effective means of contraception, * any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial, * persons protected by a legal regime (guardianship, trusteeship), * patients in emergency situations, * patients kept in detention.

Keywords: glioblastoma, thrombocytopenia, temozolomide, chemotherapy