Disulfiram in Recurrent Glioblastoma

Inclusion Criteria:

1. A previous diagnosis of glioblastoma (histologically verified) and presenting with afirst progression/recurrence documented by MRI.
2. Indication for treatment with chemotherapeutic alkylating agents (i.e. temozolomide ORlomustine including PCV treatment).
3. Age 18 years or older.
4. Karnofsky performance status of 60 - 100 .
5. Not receiving another experimental treatment for glioblastoma at the moment ofinclusion or during active treatment within the assigned group (i.e. control ordisulfiram group).
6. Able to take oral medications.
7. No known allergy to disulfiram or copper.
8. Absolute neutrophil count ≥ 1,500/mcL and platelets ≥ 100,000/mcL
9. Serum/plasma copper and serum ceruloplasmin within institutional limits. a. However increased levels are seen together with ongoing acute phase reaction asdetermined by elevated C-reactive protein (ceruloplasmin is elevated as part of thesame process) it is possible to retest after normalization of C-reactive protein.
10. Willing to refrain from ingestion of alcoholic beverages while on the study is acriteria to be randomized. However, once randomized alcohol abstinence only affectsthe group treated with disulfiram, and in this group it includes the entire period andone month after last dosage of disulfiram.

Exclusion Criteria:

1. Earlier treatment for progression (e.g. "rescue therapy")
2. History of idiopathic seizure disorder, psychosis or schizophrenia.
3. History of uncontrolled hypertension (i.e. systolic BP > 180 mmHg) and a diagnosis ofcongestive heart failure
4. Received radiotherapy within the 3 months before the diagnosis of progression .
5. Addiction to alcohol or drugs.
6. Pregnant and/or breastfeeding.
7. Women of childbearing potential who do not have negative pregnancy test not older than 14 days before enrollment.
8. History of active liver disease, including chronic active hepatitis, viral hepatitis (hepatitis B, C and CMV), cholestatic jaundice of any etiology or toxic hepatitis orinadequate hepatic function, defined as baseline ASAT and ALAT > 2.5 X upperinstitutional limit and/or bilirubin > 2.0 X upper institutional limit.
9. History of Wilson's disease or family member with Wilson's disease (unless excluded asa carrier by genetic test).
10. History of hemochromatosis or family member with hemochromatosis (unless excluded as acarrier by genetic test).
11. Nickel hypersensitivity (disulfiram mobilize nickel causing a brief increase in nickelconcentrations before excretion. The initial increase may lead to hepatitis andpredisposed patients).
12. Need for metronidazole, warfarin and/or theophylline medication (the metabolism may beinfluenced by disulfiram).
13. Patients who are taking medications metabolized by cytochrome P450 2E1, includingchlorzoxazone or halothane and its derivatives (phenytoin, phenobarbital,chlordiazepoxide, imipramine, diazepam, isoniazid, metronidazole, warfarin,amitriptyline within 14 days prior to the first dose of disulfiram. Of note, lorazepamand oxazepam are not affected by the P450 system and are not contraindicated withdisulfiram).
14. Unfit for participation for any other reason judged by the including physician.