Evidence Table 19. Description of Large Observational Toxicity Studies of Hydroxyurea Treatment in Diseases Other than Sickle Cell Disease

Author, yearLocationDesignDiseaseRecruitment start date - end dateInclusion & exclusion criteriaInterventionStarting dose: Titration DosePlanned duration/last observationTotal Q score
Yin, 2006 117North AmericaCase seriesCML Jan 1997 – Sep 2004Inclusion: t (3;21) translocation15 -HU, 1 -imatinib 2 weeks to 31 months/ last observation, median 3 months65
AML8 varieties of prior chemo: two patients had no prior therapy
Urabe, 1990 119AsiaCase seriesCMLMay 1988 - NAInclusion: CMLHUNRLast observation mean, 20.1 months*30
Vassallo, 2001 118EuropeCase seriesCML1977 - 1998Exclusion: diabetes; peripheral venous insufficiency; condylomata acuminata; cancer/precancerous lesions; exposure to carcinogens/radiation; previously treated with anything but HU; rheumatological and autoimmune disordersHU1500–2000 mg/d; reported maintenance doses of 500 to 1000 mg/d based on response54
Duletic-Nacinovic, 2000 120EuropeCohort with comparison armCMLJan 1986 – Jun 1997Inclusion: CML 1st chronic phaseHU 40 mg/kg/d: dose decreased to 20 mg/kg when WBC decreased to 20,000 63
Busulfan0.1 mg/kg/d: dose decreased by 50% when WBC decreased by 50%, discontinued when WBC dropped below 20,000
PV/ET/MF/unspecified MPD
Nielsen, 2003 134EuropeCohort with comparison armPV, ET, IMF unclassified MPDJan1993 – Dec 2000Inclusion: chronic MPD, Philadelphia chromosome negativeHU 650.1 g HU (range 1–3,200 g) 64
No drug treatment
Busulfan alone
Busulfan + HU
Anagrelide + HU
Busulfan, IFN + HU
Busulfan, Anagrelide + HU
Weinfeld, 1994 135NROther prospective cohortPV, ET, IMF1976 - NR Inclusion: myeloproliferative disordersPV/HU 30 mg/kg/d: day 8 reduced by 50% and adjusted to blood counts maintenance dose of 0.5 to 1.5 g/d) NR23
1976 - NR ET/HU 30 mg/kg/d: day 8 reduced by 50% and day 8 reduced by 50% and adjusted to blood counts (maintenance dose of .5 to 1.5 g/d)
1976 - NRMF/HU30 mg/kg/d: day 8 reduced by 50% and day 8 reduced by 50% and adjusted to blood counts (maintenance dose of .5 to 1.5 g/d)
Randi, 2005136EuropeCase seriesPV, ETInclusion: Age >60; PV or ET diagnosed by PVSG criteria; previous thrombotic event (n=72); plt count >1,500K/mlHU30 mg/kg per day4.33 years46
Randi, 2005137EuropeCase seriesPV, ETInclusion: Age >60 years; previous major thrombotic event; platelet count over 1500×109/LHU30mg/kg/day: maintenance dose 15mg/kg/dayPatients observed over a period of 20 years31
Mavrogianni, 2002 196EuropeCohort with a comparison armPV, ETNRNRPV: HU therapy NR86 ( range, 36–195) months57
ET: HU therapy
PV: busulfan
ET: alpha IFN
Finazzi, 2005 124EuropeCase seriesPV1997 - 2001Inclusion: diagnosis of PV by PVSGHU 63
Any other cytoreductive drug
No drug or alpha IFN only
West, 1987 128North AmericaCase seriesPV1963 - 1983Inclusion: PVHU500 mg: based on blood counts, mean daily dose of 720mg64.9 months33
Donovan, 1984 127North AmericaCase seriesPVInclusion: PV; off all therapy for four months prior to starting HUHU no prior treatment 30 mg/kg day × 1 week then 15 mg/kg: 5/mg/kg/d changes to keep HCT controlled 53
HU and prior myelosuppressive therapy30 mg/kg day × 1 week then 15 mg/kg: 5/mg/kg/d changes to keep HCT controlled
Najean, 1996 105EuropeCohort with a comparison armPVHU 30mg/kg/d (initial dose) 8mg/kg/d (maintenance dose) 28
Pipobroman 1.5mg/kg/d (initial dose) 0.4 mg/kg/d (maintenance dose)
32P +HU NR
32P without maintenanceNR
Wasserman Cluster/PV
Kaplan, 1986 125North AmericaCohort with a comparison arm§PVExclusion: previously treated with myelosuppresive agentsHU 61 (245 weeks)44
Fruchtman, 1997126North AmericaCohort with a comparison armPVInclusion: PVHU Last observation: 198.75 months60
Exclusion: prior chemoPhlebotomy
Chim, 2005 133Southeast AsiaCase seriesETInclusion: Essential ThrombocytosisHU alone 67
Melphalan + HU
32P + HU
Bernasconi, 2002 107EuropeCase seriesET1985 - 1995HU alone 15 mg/kg/d 67
Pipobroman 1 mg/kg/d
Gangat, 2007 106North AmericaCohort with a comparison armETJul 1956 – Dec 2005HU median follow-up for the entire study population: 84 months (range, 0–424)73
Anagrelide or IFN only
Exposure to single agent cytotoxics other than HU
No drug exposure
Anagrelide or IFN-alpha + HU
Other cytotoxics (busulfan, chlorambucil, 32P) + HU
Sterkers, 1998132EuropeCase seriesET1970 – Jan 1991Inclusion: ETHU alone 1.5 g/d Fourteen patients had received HU, during a median period of 53 months (range, 3 to 96); seven of them had received HU alone, and seven had also received other treatments
HU with other agents
32P alone 0.1 mCi/kg
32P with other agents
Busulfan alone 6 mg/d
Busulfan with other agents
Pipobroman alone 1 mg/kg/day
Pipobroman with other agents
No treatment

No data was given on the average time each patient was treated, and no info on demographics was reported.

No demographic information reported based on chemo. Data only given only by disease type.

Four patients with short-time toxicity; 12 patients with long-term side effects needing drug withdrawal; 65 patients with minor side-effects (black nail pigmentation; asymptomatic macrocytosis).


Compared two population groups from different studies.


P = radioactive phosphorus; AML = acute myelogenous leukemia; CML = chronic myelogenous leukemia; ET = Essential thrombocytopenia; HCT = hematocrit; HU = hydroxyurea; IFN = interferon; IMF = idiopathic myelofibrosis; MF = Myelofibrosis; MPD = myeloproliferative disorder; NA = not applicable; NR = not reported; plt = platelets; Pts = patients; PV = Polycythemia vera; PVSG = Polycythemia Vera Study Group; Q = quality; WBC = white blood cells.

From: Appendix C: Evidence Tables

Cover of Hydroxyurea for the Treatment of Sickle Cell Disease
Hydroxyurea for the Treatment of Sickle Cell Disease.
Evidence Reports/Technology Assessments, No. 165.
Segal JB, Strouse JJ, Beach MC, et al.

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