Intervention: Bortezomib
Trial phase: Phase 2
ATC code: L01XG01 | L01XX32
SMILES: CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)c1cnccn1)B(O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 8
Group description: Bortezomib was given at a dose of 1.3 mg per meter squared on day 1, 4, 8, and 11 on a 21 day cycle. Up to 12 cycles were allowed. Response assessments were made after the 3rd, 6th and 12 cycles of therapy.
Eligibility criteria:
DISEASE CHARACTERISTICS:

Diagnosis of myelodysplastic syndromes (MDS)

Requires treatment or transfusion support for MDS, as indicated by 1 of the following:

Demonstrates transfusion or epoetin alfa dependence

Transfusion dependence is defined as requiring ≥ 2 units of packed RBCs within an 8-week period prior to study entry

Hemoglobin < 11g/dL on 2 separate occasions 2 weeks apart

No iron, cyanocobalamin (vitamin B_12), or folic acid deficiency or other causes of anemia

Must have 1 of the following FAB subtypes:

Refractory anemia
Refractory anemia with ringed sideroblasts
Refractory anemia with excess blasts
Secondary MDS (if ≥ 3 years since active primary cancer)
No chronic myelomonocytic leukemia
Not refractory to platelet transfusion support (i.e., inability to maintain platelet count > 20,000/mm^3 with transfusion)
No current acute myelogenous leukemia (e.g., > 30% blasts)

PATIENT CHARACTERISTICS:

Performance status

Karnofsky 50-100%

Life expectancy

At least 6 months

Hematopoietic

See Disease Characteristics

Hepatic

Bilirubin ≤ 2 mg/dL
AST and ALT < 2 times upper limit of normal

Renal

Creatinine clearance ≥ 30 mL/min

Cardiovascular

No significant cardiovascular condition that would preclude study participation
No uncontrolled hypertension

Pulmonary

No significant pulmonary condition that would preclude study participation

Immunologic

No serious concurrent infection

Active infections must be adequately treated with antibiotics prior to study entry
No hypersensitivity to bortezomib, boron, or mannitol

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for up to 4 weeks after completion of study treatment
No peripheral neuropathy ≥ grade 2
No uncontrolled seizure activity, as defined by no activity within the past year on stable anticonvulsant medications
No other malignancy within the past 3 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
No endocrine, neurologic, or other systemic disease that would preclude study entry

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
No prior allogeneic bone marrow transplantation
Concurrent transfusion support allowed
Concurrent epoetin alfa or darbepoetin alfa allowed if initiated before start of study therapy, dose is stable for ≥ 4 weeks, and dose is stable during study participation
No concurrent platelet growth factor support
No concurrent thalidomide

Chemotherapy

No concurrent chemotherapy
No concurrent hydroxyurea

Endocrine therapy

Concurrent corticosteroids for chronic autoimmune or inflammatory condition allowed if initiated before start of study therapy and maintained on a stable or decreasing dose

Other

Recovered from all prior therapies
At least 4 weeks since prior MDS therapy, except epoetin alfa, darbepoetin alfa, filgrastim (G-CSF), pegfilgrastim (G-CSF), or transfusion support
At least 30 days since prior investigational agents
No prior bortezomib
No other concurrent investigational agents
No other concurrent therapy for MDS