Dasatinib (SPIRIT 2 Trial)

Transcription

1 Dasatinib (SPIRIT 2 Trial) SPIRIT2 - STI571 Prospective International RandomIsed Trial 2 - A phase III, prospective randomised comparison of imatinib (STI571, Glivec or licensed generic) 400mg daily versus dasatinib 100mg in patients with newly-diagnosed chronic phase chronic myeloid leukaemia. *** See trial protocol for further details *** Available for Routine Use in Burton in-patient N/A Derby in-patient Burton day-case Derby day-case Burton outreach chemotherapy clinic N/A Derby outreach chemotherapy clinic Burton out-patient Derby out-patient Indication Newly-diagnosed (within last 3 months) chronic phase chronic myeloid leukaemia Treatment Intent Palliative Anti-Emetics Pre-chemotherapy Nil Post-chemotherapy A Frequency & Continuously until disease progression Duration Day 1 Dasatinib 100mg Oral ONCE daily Metoclopramide 10mg Oral four times daily as required Notes: 1. Patients reaching visit 15 have reached the end of the study and revert to standard care. However, patients who have remained on 100mg Dasatinib are assured a continued free of charge supply of Dasatinib through the trial until the last patient reaches visit 15, i.e. March Dasatinib tablets should be taken by mouth with a drink of water and swallowed whole. 3. Patients should avoid grapefruit juice while taking dasatinib as this may alter dasatinib levels (CYP3A4 substrate). AUTHORISED BY Dr J Addada PAGE 1 of 5

2 4. Wherever possible, patients should take the standard dose of 100mg once daily. There are occasions where patients cannot tolerate the standard dose, usually due to toxicity, and in these circumstances the dose reduction and re-escalation schedules below should be used. Every attempt should be made to dose re-escalate to the standard dose. If a patient cannot tolerate the standard dose, every effort should be made to give them as much study drug as possible with repeated attempts at dose escalation. Patients will be allowed to continue allocated study drug on whatever dose they can sustain as long as there is adequate disease control. 5. Dose modifications and toxicities The dose modification guidelines below MUST be followed for patients with: haematological abnormalities (platelets, neutrophils, WBC) abnormal liver function tests (AST/ALT) pleural effusion (diuretics and chest drains are not usually required to treat pleural effusions) toxicities where the study drug is the suspected cause (See Protocol section 7 for more details). In certain circumstances it may not be appropriate to modify dose according to the guidelines. If there are clinical reasons for not following the dose modification guidelines please call the trial office to discuss before proceeding. AUTHORISED BY Dr J Addada PAGE 2 of 5

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4 Patients with Shortness of Breath It has been noted that dasatinib can cause Pulmonary Arterial Hypertension (PAH), pleural effusions and shortness of breath. Please see section of Protocol for dose modification details for this toxicity. 6. Concomitant medication Caution should be taken when administering dasatinib with inhibitors/inducers of the CYP34A family: Substances that inhibit cytochrome P450 isoenzyme CYP3A4 activity (e.g. ketoconazole, itraconazole, erythromycin, clarithromycin) can decrease metabolism and increase dasatinib concentrations. Substances that induce cytochrome P450 isoenzyme CYP3A4 activity (e.g. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbitone, St John s Wort) could increase metabolism and reduce dasatinib concentrations. Caution should be exercised when using dasatinib and paracetamol concomitantly, especially high doses of paracetamol. Grapefruit juice should be avoided. Anagrelide and hydroxycarbamide are NOT permitted after the first month of dasatinib therapy. If the patient s count is such as to require these medications after the first month AUTHORISED BY Dr J Addada PAGE 4 of 5

5 of dasatinib therapy, this will be regarded as a treatment failure and the patient will go off study. The use of GCSF is permitted and should be recorded as a concomitant medication. Caution should be exercised in prescribing drugs which are known to prolong the QT interval and if such drugs are necessary for the patient s wellbeing more frequent ECG monitoring might be advisable. Supportive care None References 1. SPIRIT 2 Trial Protocol, Version 2.1, 12 th December Spirit 2 Newsletter, February 2014 AUTHORISED BY Dr J Addada PAGE 5 of 5