Clofarabine
2273573
200786189
2008-03-25T12:51:24Z
Carlo Banez
5493017
/* External links */
{{drugbox | IUPAC_name = 5-(6-amino-2-chloro-purin-9-yl) -4-fluoro-2- (hydroxymethyl)oxolan-3-ol | image = Clofarabine.svg | CAS_number = 123318-82-1 | ATC_prefix = L01 | ATC_suffix = BB06 | ATC_supplemental = | PubChem = 119182 | DrugBank = APRD00878 | C = 10 | H = 1 | Cl = 1 | F = 1 | N = 5 | O = 3 | molecular_weight = 303.677 g/mol | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | pregnancy_category = | legal_status = | routes_of_administration = }}
'''Clofarabine''' is a substance that is being studied in the treatment of [[cancer]]. It is a [[purine]] [[nucleoside]] [[antimetabolite]]. It is marketed in the [[United States|U.S.]] and [[Canada]] as '''Clolar'''. In [[Europe]] and [[Australia]]/[[New Zealand]] the product is marketed under the name '''Evoltra'''.
It is used in [[paediatric]]s to treat a type of [[leukaemia]] called relapsed or refractory [[acute lymphoblastic leukaemia]] (ALL), only after at least two other types of treatment have failed. It is not known if extends life expectancy. Some investigations of effectiveness in cases of [[acute myeloid leukaemia]] (AML) and juvenile myelomonocytic leukaemia (JMML) have been carried out.
==Side effects==
* [[Tumor lysis syndrome]] (TLS). Clofarabine quickly kills leukaemia cells in the blood. The body may react to this. Symptoms include fast breathing, fast heartbeat, low blood pressure, and fluid in the lungs. TLS is very serious and can lead to death if it is not treated right away.
*Bone marrow problems (suppression). Clofarabine can stop the bone marrow from making enough [[red blood cells]], [[white blood cells]], and [[platelets]]. Serious side effects that can happen because of bone marrow suppression include severe infection ([[sepsis]]), bleeding, and [[anemia]].
*Effects on [[pregnancy]] and [[breastfeeding]]. Girls and women should not become pregnant or breastfeed during treatment which harm the baby.
*[[Dehydration]] and [[low blood pressure]]. Clofarabine can cause [[vomit]]ing and [[diarrhea]] which may lead to low body fluid (dehydration). Signs and symptoms of dehydration include dizziness, lightheadedness, fainting spells, or decreased [[urination]].
*Other side effects. The most common side effects are stomach problems (including vomiting, diarrhea, and [[nausea]]), and effects on blood cells (including low red blood cells count, low white blood cell count, low platelet count, [[fever]], and infection. Clofarabine can also cause [[tachycardia]] and can affect the [[liver]] and [[kidneys]].
==Contraindications==
*pregnancy or planned pregnancy
*breast-feeding
*liver problems
*kidney problems
==Drug interactions==
*nephrotoxic drugs
*hepatotoxic drugs
==Delivery==
*By [[intravenous infusion]].
*Dosage is a 2 hour infusion (52 mg/m²) every day for five days. The cycle is repeated every 2 to 6 weeks.
*Regular blood tests to monitor his or her blood cells, kidney function, and liver function.
==Results of clinical trials==
Efficacy and safety were demonstrated in a single multi-center trial that enrolled 40 patients aged 2-19. The patients were suffering with relapsed or refractory acute lymphoblastic leukaemia (ALL) (An additional 9 patients suffering with [[acute myelogenous leukaemia]] (AML) had similar [[pharmacokinetics]] but are not included in the figure below.) Most patients had received 2 to 4 prior regimens and 15/49 (31%) had undergone at least one [[Organ transplant|transplant]]. The median age was 12 years. Clofarabine was given at a dose of 52 mg/m<sup>2</sup>, intravenously, over 2 hours daily x 5 repeated every 2 to 6 weeks following recovery or return to baseline organ function. The study endpoints were the rate of complete response (CR) and the rate of complete response without platelet recovery (CRp). The former was defined as no evidence of circulating [[blast]]s or extramedullary disease, an M1 [[bone marrow]], and recovery of peripheral platelet and absolute [[neutrophil]] counts; the latter was defined as meeting all criteria for CR except for platelet count recovery. Response rates were determined by an Independent Response Review Panel (IRRP).
Six patients (12%) achieved a CR and 4 patients (8%) achieved a CRp, and 5 patients (10%) achieved a PR. Of the 15 responding patients, 6 had post-clofarabine bone marrow transplantation. Hence, response durations could not be determined. In the patients who were not transplanted, the response durations for CR were 43, 50, 82, 93+, and 160+ days; for CRp the response duration was 32 days.
The principal clofarabine toxicities were nausea, vomiting, hematologic toxicity, [[febrile neutropenia]], [[hepatobiliary toxicity]], infections and renal toxicity. Clofarabine can produce [[systemic inflammatory response syndrome]]/[[capillary leak syndrome]] (SIRS), manifested by the rapid development of [[tachypnea]], tachycardia, [[hypotension]], shock, and multi-organ failure. Cardiac toxicity was characterized as [[left ventricle|left ventricular]] [[systolic dysfunction]]; tachycardia may also occur.
==Approval==
Clolar was [[Food and Drug Administration]] (FDA) Approved [[28 December]] [[2004]]. (Under accelerated approval regulations requiring further clinical studies.)
==Patents==
*{{US patent|4751221}}
*{{US patent|4918179}}
*{{US patent|5384310}}
*{{US patent|5661136}}
*{{US patent|6680382}}
==External links==
* [http://www.cancerbackup.org.uk/Treatments/Chemotherapy/Individualdrugs/Clofarabine Clofarabine information on Cancerbackup.]
* [http://www.fda.gov/cder/foi/label/2004/021673lbl.pdf FDA usage leaflet.]
* [http://www.clolar.com/ Clolar.com homepage.]
* [http://www.genzymeoncology.com/onc/products/clolar/onc_p_clolar.asp FDA approval notice.]
{{Chemotherapeutic agents}}
[[Category:Chemotherapeutic agents]]
[[Category:Organofluorides]]