DACOGEN is a cytotoxic drug. Follow special handling and disposal procedures.¹

Aseptically reconstitute DACOGEN with room temperature (20°C to 25°C) 10 mL of Sterile Water for Injection, USP. Upon reconstitution, the final concentration of the reconstituted DACOGEN solution is 5 mg/mL. You must dilute the reconstituted solution with 0.9% Sodium Chloride Injection or 5% Dextrose Injection prior to administration. Temperature of the diluent (0.9% Sodium Chloride Injection or 5% Dextrose Injection) depends on time of administration after preparation.

Fatal and serious myelosuppression occurs in DACOGEN-treated patients. Myelosuppression (anemia, neutropenia, and thrombocytopenia) is the most frequent cause of DACOGEN dose reduction, delay, and discontinuation. Neutropenia of any grade occurred in 90% of DACOGEN-treated patients with grade 3 or 4 occurring in 87% of patients. Grade 3 or 4 febrile neutropenia occurred in 23% of patients. Thrombocytopenia of any grade occurred in 89% of patients with grade 3 or 4 occurring in 85% of patients. Anemia of any grade occurred in 82% of patients. Perform complete blood count with platelets at baseline, prior to each cycle, and as needed to monitor response and toxicity. Manage toxicity using dose-delay, dose-reduction, growth factors, and anti-infective therapies as needed [see Dosage and Administration (2.2)]. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying MDS.

Based on findings from human data, animal studies and its mechanism of action, DACOGEN can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1)]. In preclinical studies in mice and rats, decitabine caused adverse developmental outcomes including embryo-fetal lethality and malformations. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception while receiving DACOGEN and for 6 months following the last dose. Advise males with female partners of reproductive potential to use effective contraception while receiving treatment with DACOGEN and for 3 months following the last dose [see Use in Specific Populations (8.1, 8.3)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of DACOGEN was studied in 3 single-arm studies (N =66, N =98, N =99) and 1 controlled supportive care study (N =83 DACOGEN, N =81 supportive care). The data described below reflect exposure to DACOGEN in 83 patients in the MDS trial. In the trial, patients received 15 mg/m² intravenously every 8 hours for 3 days every 6 weeks. The median number of DACOGEN cycles was 3 (range 0 to 9).

Most Common Adverse Reactions: neutropenia, thrombocytopenia, anemia, fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, and hyperglycemia.

Adverse Reactions Most Frequently (≥1%) Resulting in Clinical Intervention and or Dose Modification in the Controlled Supportive Care Study in the DACOGEN Arm:

• Discontinuation: thrombocytopenia, neutropenia, pneumonia, Mycobacterium avium complex infection, cardio-respiratory arrest, increased blood bilirubin, intracranial hemorrhage, abnormal liver function tests.
• Dose Delayed: neutropenia, pulmonary edema, atrial fibrillation, central line infection, febrile neutropenia.
• Dose Reduced: neutropenia, thrombocytopenia, anemia, lethargy, edema, tachycardia, depression, pharyngitis.

Table 1 presents all adverse reactions occurring in at least 5% of patients in the DACOGEN group and at a rate greater than supportive care.

Table 1 Adverse Reactions Reported in ≥5% of Patients in the DACOGEN Group and at a Rate Greater than Supportive Care in the Controlled Trial in MDS

	DACOGEN N =83 (%)	Supportive Care N =81 (%)
Blood and lymphatic system disorders
  Neutropenia	75 (90)	58 (72)
  Thrombocytopenia	74 (89)	64 (79)
  Anemia NOS	68 (82)	60 (74)
  Febrile neutropenia	24 (29)	5 (6)
  Leukopenia NOS	23 (28)	11 (14)
  Lymphadenopathy	10 (12)	6 (7)
  Thrombocythemia	4 (5)	1 (1)
Cardiac disorders
  Pulmonary edema NOS	5 (6)	0 (0)
Eye disorders
  Vision blurred	5 (6)	0 (0)
Gastrointestinal disorders
  Nausea	35 (42)	13 (16)
  Constipation	29 (35)	11 (14)
  Diarrhea NOS	28 (34)	13 (16)
  Vomiting NOS	21 (25)	7 (9)
  Abdominal pain NOS	12 (14)	5 (6)
  Oral mucosal petechiae	11 (13)	4 (5)
  Stomatitis	10 (12)	5 (6)
  Dyspepsia	10 (12)	1 (1)
  Ascites	8 (10)	2 (2)
  Gingival bleeding	7 (8)	5 (6)
  Hemorrhoids	7 (8)	3 (4)
  Loose stools	6 (7)	3 (4)
  Tongue ulceration	6 (7)	2 (2)
  Dysphagia	5 (6)	2 (2)
  Oral soft tissue disorder NOS	5 (6)	1 (1)
  Lip ulceration	4 (5)	3 (4)
  Abdominal distension	4 (5)	1 (1)
  Abdominal pain upper	4 (5)	1 (1)
  Gastro-esophageal reflux disease	4 (5)	0 (0)
  Glossodynia	4 (5)	0 (0)
General disorders and administrative site disorders
  Pyrexia	44 (53)	23 (28)
  Edema peripheral	21 (25)	13 (16)
  Rigors	18 (22)	14 (17)
  Edema NOS	15 (18)	5 (6)
  Pain NOS	11 (13)	5 (6)
  Lethargy	10 (12)	3 (4)
  Tenderness NOS	9 (11)	0 (0)
  Fall	7 (8)	3 (4)
  Chest discomfort	6 (7)	3 (4)
  Intermittent pyrexia	5 (6)	3 (4)
  Malaise	4 (5)	1 (1)
  Crepitations NOS	4 (5)	1 (1)
  Catheter site erythema	4 (5)	1 (1)
  Catheter site pain	4 (5)	0 (0)
  Injection site swelling	4 (5)	0 (0)
Hepatobiliary disorders
  Hyperbilirubinemia	12 (14)	4 (5)
Infections and infestations
  Pneumonia NOS	18 (22)	11 (14)
  Cellulitis	10 (12)	6 (7)
  Candidal infection NOS	8 (10)	1 (1)
  Catheter related infection	7 (8)	0 (0)
  Urinary tract infection NOS	6 (7)	1 (1)
  Staphylococcal infection	6 (7)	0 (0)
  Oral candidiasis	5 (6)	2 (2)
  Sinusitis NOS	4 (5)	2 (2)
  Bacteremia	4 (5)	0 (0)
Injury, poisoning and procedural complications
  Transfusion reaction	6 (7)	3 (4)
  Abrasion NOS	4 (5)	1 (1)
Investigations
  Cardiac murmur NOS	13 (16)	9 (11)
  Blood alkaline phosphatase NOS increased	9 (11)	7 (9)
  Aspartate aminotransferase increased	8 (10)	7 (9)
  Blood urea increased	8 (10)	1 (1)
  Blood lactate dehydrogenase increased	7 (8)	5 (6)
  Blood albumin decreased	6 (7)	0 (0)
  Blood bicarbonate increased	5 (6)	1 (1)
  Blood chloride decreased	5 (6)	1 (1)
  Protein total decreased	4 (5)	3 (4)
  Blood bicarbonate decreased	4 (5)	1 (1)
  Blood bilirubin decreased	4 (5)	1 (1)
Metabolism and nutrition disorders
  Hyperglycemia NOS	27 (33)	16 (20)
  Hypoalbuminemia	20 (24)	14 (17)
  Hypomagnesemia	20 (24)	6 (7)
  Hypokalemia	18 (22)	10 (12)
  Hyponatremia	16 (19)	13 (16)
  Appetite decreased NOS	13 (16)	12 (15)
  Anorexia	13 (16)	8 (10)
  Hyperkalemia	11 (13)	3 (4)
  Dehydration	5 (6)	4 (5)
Musculoskeletal and connective tissue disorders
  Arthralgia	17 (20)	8 (10)
  Pain in limb	16 (19)	8 (10)
  Back pain	14 (17)	5 (6)
  Chest wall pain	6 (7)	1 (1)
  Musculoskeletal discomfort	5 (6)	0 (0)
  Myalgia	4 (5)	1 (1)
Nervous system disorders
  Headache	23 (28)	11 (14)
  Dizziness	15 (18)	10 (12)
  Hypoesthesia	9 (11)	1 (1)
Psychiatric disorders
  Insomnia	23 (28)	11 (14)
  Confusional state	10 (12)	3 (4)
  Anxiety	9 (11)	8 (10)
Renal and urinary disorders
  Dysuria	5 (6)	3 (4)
  Urinary frequency	4 (5)	1 (1)
Respiratory, thoracic and Mediastinal disorders
  Cough	33 (40)	25 (31)
  Pharyngitis	13 (16)	6 (7)
  Crackles lung	12 (14)	1 (1)
  Breath sounds decreased	8 (10)	7 (9)
  Hypoxia	8 (10)	4 (5)
  Rales	7 (8)	2 (2)
  Postnasal drip	4 (5)	2 (2)
Skin and subcutaneous tissue disorders
  Ecchymosis	18 (22)	12 (15)
  Rash NOS	16 (19)	7 (9)
  Erythema	12 (14)	5 (6)
  Skin lesion NOS	9 (11)	3 (4)
  Pruritis	9 (11)	2 (2)
  Alopecia	7 (8)	1 (1)
  Urticaria NOS	5 (6)	1 (1)
  Swelling face	5 (6)	0 (0)
Vascular disorders
  Petechiae	32 (39)	13 (16)
  Pallor	19 (23)	10 (12)
  Hypotension NOS	5 (6)	4 (5)
  Hematoma NOS	4 (5)	3 (4)

In a single-arm MDS study (N=99), DACOGEN was dosed at 20 mg/m² intravenously, infused over one hour daily, for 5 consecutive days of a 4-week cycle. Table 2 presents all adverse reactions occurring in at least 5% of patients.

Table 2 Adverse Reactions Reported in ≥5% of Patients in a Single-arm StudyIn this single arm study, investigators reported adverse events based on clinical signs and symptoms rather than predefined laboratory abnormalities. Thus, not all laboratory abnormalities were recorded as adverse events.

	DACOGEN N =99 (%)
Blood and lymphatic system disorders
  Anemia	31 (31)
  Febrile neutropenia	20 (20)
  Leukopenia	6 (6)
  Neutropenia	38 (38)
  Pancytopenia	5 (5)
  Thrombocythemia	5 (5)
  Thrombocytopenia	27 (27)
Cardiac disorders
  Cardiac failure congestive	5 (5)
  Tachycardia	8 (8)
Ear and labyrinth disorders
  Ear pain	6 (6)
Gastrointestinal disorders
  Abdominal pain	14 (14)
  Abdominal pain upper	6 (6)
  Constipation	30 (30)
  Diarrhea	28 (28)
  Dyspepsia	10 (10)
  Dysphagia	5 (5)
  Gastro-esophageal reflux disease	5 (5)
  Nausea	40 (40)
  Oral pain	5 (5)
  Stomatitis	11 (11)
  Toothache	6 (6)
  Vomiting	16 (16)
General disorders and administration site conditions
  Asthenia	15 (15)
  Chest pain	6 (6)
  Chills	16 (16)
  Fatigue	46 (46)
  Mucosal inflammation	9 (9)
  Edema	5 (5)
  Edema peripheral	27 (27)
  Pain	5 (5)
  Pyrexia	36 (36)
Infections and infestations
  Cellulitis	9 (9)
  Oral candidiasis	6 (6)
  Pneumonia	20 (20)
  Sinusitis	6 (6)
  Staphylococcal bacteremia	8 (8)
  Tooth abscess	5 (5)
  Upper respiratory tract infection	10 (10)
  Urinary tract infection	7 (7)
Injury, poisoning and procedural complications
  Contusion	9 (9)
Investigations
  Blood bilirubin increased	6 (6)
  Breath sounds abnormal	5 (5)
  Weight decreased	9 (9)
Metabolism and nutrition disorders
  Anorexia	23 (23)
  Decreased appetite	8 (8)
  Dehydration	8 (8)
  Hyperglycemia	6 (6)
  Hypokalemia	12 (12)
  Hypomagnesemia	5 (5)
Musculoskeletal and connective tissue disorders
  Arthralgia	17 (17)
  Back pain	18 (18)
  Bone pain	6 (6)
  Muscle spasms	7 (7)
  Muscular weakness	5 (5)
  Musculoskeletal pain	5 (5)
  Myalgia	9 (9)
  Pain in extremity	18 (18)
Nervous system disorders
  Dizziness	21 (21)
  Headache	23 (23)
Psychiatric disorders
  Anxiety	9 (9)
  Confusional state	8 (8)
  Depression	9 (9)
  Insomnia	14 (14)
Respiratory, thoracic and mediastinal disorders
  Cough	27 (27)
  Dyspnea	29 (29)
  Epistaxis	13 (13)
  Pharyngolaryngeal pain	8 (8)
  Pleural effusion	5 (5)
  Sinus congestion	5 (5)
Skin and subcutaneous tissue disorders
  Dry skin	8 (8)
  Ecchymosis	9 (9)
  Erythema	5 (5)
  Night sweats	5 (5)
  Petechiae	12 (12)
  Pruritus	9 (9)
  Rash	11 (11)
  Skin lesion	5 (5)
Vascular disorders
  Hypertension	6 (6)
  Hypotension	11 (11)

No overall difference in safety was detected between patients >65 years of age and younger patients in these MDS trials. No significant differences in safety were detected between males and females. Patients with renal or hepatic dysfunction were not studied. Insufficient numbers of non-White patients were available to draw conclusions in these clinical trials.

Serious adverse reactions that occurred in patients receiving DACOGEN not previously reported in Tables 1 and 2 include:

• Allergic Reaction: hypersensitivity (anaphylactic reaction)
• Blood and Lymphatic System Disorders: myelosuppression, splenomegaly
• Cardiac Disorders: myocardial infarction, cardio-respiratory arrest, cardiomyopathy, atrial fibrillation, supraventricular tachycardia
• Gastrointestinal Disorders: gingival pain, upper gastrointestinal hemorrhage
• General Disorders and Administrative Site Conditions: chest pain, catheter site hemorrhage
• Hepatobiliary Disorders: cholecystitis
• Infections and Infestations: fungal infection, sepsis, bronchopulmonary aspergillosis, peridiverticular abscess, respiratory tract infection, pseudomonal lung infection, Mycobacterium avium complex infection
• Injury, Poisoning and Procedural Complications: post procedural pain, post procedural hemorrhage
• Nervous System Disorders: intracranial hemorrhage
• Psychiatric Disorders: mental status changes
• Renal and Urinary Disorders: renal failure, urethral hemorrhage
• Respiratory, Thoracic and Mediastinal Disorders: hemoptysis, lung infiltration, pulmonary embolism, respiratory arrest, pulmonary mass

The following adverse reactions have been identified during postapproval use of DACOGEN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Sweet's syndrome (acute febrile neutrophilic dermatosis)
• Differentiation syndrome
• Interstitial lung disease

The safety and effectiveness of DACOGEN in pediatric patients have not been established.

Of the total number of patients exposed to DACOGEN in the controlled clinical trial, 61 of 83 patients were age 65 years and over, while 21 of 83 patients were age 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Decitabine is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into DNA and inhibition of DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation or apoptosis. Decitabine inhibits DNA methylation in vitro, which is achieved at concentrations that do not cause major suppression of DNA synthesis. Decitabine-induced hypomethylation in neoplastic cells may restore normal function to genes that are critical for the control of cellular differentiation and proliferation. In rapidly dividing cells, the cytotoxicity of decitabine may also be attributed to the formation of covalent adducts between DNA methyltransferase and decitabine incorporated into DNA. Non-proliferating cells are relatively insensitive to decitabine.

Decitabine has been shown to induce hypomethylation both in vitro and in vivo. However, there have been no studies of decitabine-induced hypomethylation and pharmacokinetic parameters.

Pharmacokinetic (PK) parameters were evaluated in patients. Eleven patients received 20 mg/m² infused over 1 hour intravenously (treatment Option 2). Fourteen patients received 15 mg/m² infused over 3 hours intravenously (treatment Option 1). PK parameters are shown in Table 3. Plasma concentration-time profiles after discontinuation of infusion showed a biexponential decline. The clearance (CL) of decitabine was higher following treatment Option 2. Upon repeat doses, there was no systemic accumulation of decitabine or any changes in PK parameters. Population PK analysis (N=35) showed that the cumulative AUC per cycle for treatment Option 2 was 2.3-fold lower than the cumulative AUC per cycle following treatment Option 1.

Table 3 Mean (CV% or 95% CI) Pharmacokinetic Parameters of Decitabine

Dose	Cmax (ng/mL)	AUC0-INF (ng∙h/mL)	T1/2 (h)	CL (L/h/m2)	AUCCumulative N=35 Cumulative AUC per cycle (ng∙h/mL)
15 mg/m2 3-hr infusion every 8 hours for 3 days (Option 1)N=14,	73.8 (66)	163 (62)	0.62 (49)	125 (53)	1332 (1010-1730)
20 mg/m2 1-hr infusion daily for 5 days (Option 2)N=11,	147 (49)	115 (43)	0.54 (43)	210 (47)	570 (470-700)

The exact route of elimination and metabolic fate of decitabine is not known in humans. One of the pathways of elimination of decitabine appears to be deamination by cytidine deaminase found principally in the liver but also in granulocytes, intestinal epithelium and whole blood.

Carcinogenicity studies with decitabine have not been conducted.

The mutagenic potential of decitabine was tested in several in vitro and in vivo systems. Decitabine increased mutation frequency in L5178Y mouse lymphoma cells, and mutations were produced in an Escherichia coli lac-I transgene in colonic DNA of decitabine-treated mice. Decitabine caused chromosomal rearrangements in larvae of fruit flies.

In male mice given IP injections of 0.15, 0.3 or 0.45 mg/m² decitabine (approximately 0.3% to 1% the recommended clinical dose) 3 times a week for 7 weeks, decitabine did not affect survival, body weight gain or hematological measures (hemoglobin and white blood cell counts). Testes weights were reduced, abnormal histology was observed and significant decreases in sperm number were found at doses ≥0.3 mg/m². In females mated to males dosed with ≥0.3 mg/m² decitabine, pregnancy rate was reduced and preimplantation loss was significantly increased.

A randomized open-label, multicenter, controlled trial evaluated 170 adult patients with myelodysplastic syndromes (MDS) meeting French-American-British (FAB) classification criteria and International Prognostic Scoring System (IPSS) High-Risk, Intermediate-2 and Intermediate-1 prognostic scores. Eighty-nine patients were randomized to DACOGEN therapy plus supportive care (only 83 received DACOGEN), and 81 to Supportive Care (SC) alone. Patients with Acute Myeloid Leukemia (AML) were not intended to be included. Of the 170 patients included in the study, independent review (adjudicated diagnosis) found that 12 patients (9 in the DACOGEN arm and 3 in the SC arm) had the diagnosis of AML at baseline. Baseline demographics and other patient characteristics in the Intent-to-Treat (ITT) population were similar between the 2 groups, as shown in Table 4.

Table 4 Baseline Demographics and Other Patient Characteristics (ITT)

Demographic or Other Patient Characteristic	DACOGEN N =89	Supportive Care N =81
Age (years)
Mean (±SD)	69±10	67±10
Median (IQR)	70 (65-76)	70 (62-74)
(Range: min-max)	(31-85)	(30-82)
Sex n (%)
Male	59 (66)	57 (70)
Female	30 (34)	24 (30)
Race n (%)
White	83 (93)	76 (94)
Black	4 (4)	2 (2)
Other	2 (2)	3 (4)
Weeks Since MDS Diagnosis
Mean (±SD)	86±131	77±119
Median (IQR)	29 (10-87)	35 (7-98)
(Range: min-max)	(2-667)	(2-865)
Previous MDS Therapy n (%)
Yes	27 (30)	19 (23)
No	62 (70)	62 (77)
RBC Transfusion Status n (%)
Independent	23 (26)	27 (33)
Dependent	66 (74)	54 (67)
Platelet Transfusion Status n (%)
Independent	69 (78)	62 (77)
Dependent	20 (22)	19 (23)
IPSS Classification n (%)
Intermediate-1	28 (31)	24 (30)
Intermediate-2	38 (43)	36 (44)
High Risk	23 (26)	21 (26)
FAB Classification n (%)
RA	12 (13)	12 (15)
RARS	7 (8)	4 (5)
RAEB	47 (53)	43 (53)
RAEB-t	17 (19)	14 (17)
CMML	6 (7)	8 (10)

Patients randomized to the DACOGEN arm received DACOGEN intravenously infused at a dose of 15 mg/m² over a 3-hour period, every 8 hours, for 3 consecutive days. This cycle was repeated every 6 weeks, depending on the patient's clinical response and toxicity. Supportive care consisted of blood and blood product transfusions, prophylactic antibiotics, and hematopoietic growth factors. The study endpoints were overall response rate (complete response + partial response) and time to AML or death. Responses were classified using the MDS International Working Group (IWG) criteria; patients were required to be RBC and platelet transfusion independent during the time of response. Response criteria are given in Table 5.

Table 5 Response Criteria for the Controlled Trial in MDSCheson BD, Bennett JM, et al. Report of an International Working Group to Standardize Response Criteria for MDS. Blood. 2000; 96:3671-3674.

Complete Response (CR) ≥8 weeks	Bone Marrow	On repeat aspirates: <5% myeloblasts No dysplastic changes
	Peripheral Blood	In all samples during response: Hgb >11 g/dL (no transfusions or erythropoietin ANC ≥1500/μL (no growth factor) Platelets ≥100,000/μL (no thrombopoietic agent) No blasts and no dysplasia
Partial Response (PR) ≥8 weeks	Bone Marrow	On repeat aspirates: ≥50% decrease in blasts over pretreatment values OR Improvement to a less advanced MDS FAB classification
	Peripheral Blood	Same as for CR

The overall response rate (CR+PR) in the ITT population was 17% in DACOGEN-treated patients and 0% in the SC group (p<0.001) (see Table 6 ). The overall response rate was 21% (12/56) in DACOGEN-treated patients considered evaluable for response (i.e., those patients with pathologically confirmed MDS at baseline who received at least 2 cycles of treatment). The median duration of response (range) for patients who responded to DACOGEN was 288 days (116-388) and median time to response (range) was 93 days (55-272). All but one of the DACOGEN-treated patients who responded did so by the fourth cycle. Benefit was seen in an additional 13% of DACOGEN-treated patients who had hematologic improvement, defined as a response less than PR lasting at least 8 weeks, compared to 7% of SC patients. DACOGEN treatment did not significantly delay the median time to AML or death versus supportive care.

Table 6 Analysis of Response (ITT)

Parameter	DACOGEN N=89	Supportive Care N=81
Overall Response Rate (CR+PR)In the statistical analysis plan, a p-value of ≤0.024 was required to achieve statistical significance.	15 (17%)p-value <0.001 from two-sided Fisher's Exact Test comparing DACOGEN vs. Supportive Care.	0 (0%)
  Complete Response (CR)	8 (9%)	0 (0%)
  Partial Response (PR)	7 (8%)	0 (0%)
Duration of Response
  Median time to (CR+PR) response - Days (range)	93 (55-272)	NA
  Median Duration of (CR+PR) response - Days (range)	288 (116-388)	NA

All patients with a CR or PR were RBC and platelet transfusion independent in the absence of growth factors.

Responses occurred in patients with an adjudicated baseline diagnosis of AML.

Three open-label, single-arm, multicenter studies were conducted to evaluate the safety and efficacy of DACOGEN in MDS patients with any of the FAB subtypes. In one study conducted in North America, 99 patients with IPSS Intermediate-1, Intermediate-2, or high-risk prognostic scores received DACOGEN 20 mg/m² as an intravenous infusion over 1-hour daily, on days 1-5 of week 1 every 4 weeks (1 cycle). The results were consistent with the results of the controlled trial and are summarized in Table 8.

Table 7 Baseline Demographics and Other Patient Characteristics (ITT)

Demographic or Other Patient Characteristic	DACOGEN N =99
Age (years)
Mean (±SD)	71±9
Median (Range: min-max)	72 (34-87)
Sex n (%)
Male	71 (72)
Female	28 (28)
Race n (%)
White	86 (87)
Black	6 (6)
Asian	4 (4)
Other	3 (3)
Days From MDS Diagnosis to First Dose
Mean (±SD)	444±626
Median (Range: min-max)	154 (7-3079)
Previous MDS Therapy n (%)
Yes	27 (27)
No	72 (73)
RBC Transfusion Status n (%)
Independent	33 (33)
Dependent	66 (67)
Platelet Transfusion Status n (%)
Independent	84 (85)
Dependent	15 (15)
IPSS Classification n (%)
Low Risk	1 (1)
Intermediate–1	52 (53)
Intermediate–2	23 (23)
High Risk	23 (23)
FAB Classification n (%)
RA	20 (20)
RARS	17 (17)
RAEB	45 (45)
RAEB-t	6 (6)
CMML	11 (11)

Table 8 Analysis of Response (ITT)Cheson BD, Bennett JM, et al. Report of an International Working Group to Standardize Response Criteria for MDS. Blood. 2000; 96:3671-3674.

Parameter	DACOGEN N=99
Overall Response Rate (CR+PR)	16 (16%)
  Complete Response (CR)	15 (15%)
  Partial Response (PR)	1 (1%)
Duration of Response
Median time to (CR+PR) response - Days (range)	162 (50-267)
Median Duration of (CR+PR) response - Days (range)	443 (72-722indicates censored observation)

Store vials at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].

Myelosuppression

Advise patients of the risk of myelosuppression and to report any symptoms of infection, anemia, or bleeding to their healthcare provider as soon as possible. Advise patients for the need for laboratory monitoring [see Warnings and Precautions (5.1)].

Embryo-Fetal Toxicity

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1)].

Advise females of reproductive potential to use effective contraception while receiving DACOGEN and for 6 months after last dose [see Use in Specific Populations (8.3)].

Advise males with female partners of reproductive potential to use effective contraception while receiving treatment with DACOGEN and for 3 months after the last dose [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1)].

Lactation

Advise women to avoid breastfeeding while receiving DACOGEN and for at least 2 weeks after the last dose [see Use in Specific Populations (8.2)].