ADVERSE REACTIONS
The most common adverse reactions observed in patients with peripheral T-cell lymphoma (PTCL) treated with FOLOTYN were mucositis, thrombocytopenia, nausea, and fatigue.
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
The safety of FOLOTYN was evaluated in 111 PTCL patients in a single-arm clinical study in which patients received a starting dose of 30 mg/m2 once weekly for 6 weeks in 7-week cycles. The median duration of treatment was 70 days (range 1-540 days).
Most Frequent Adverse Reactions
Table 4 summarizes the most frequent adverse reactions, regardless of causality, using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE, version 3.0).
Table 4 Adverse Reactions Occurring in PTCL Patients (Incidence ≥ 10% of patients)
|
N=111
|
|
Total
|
Grade 3
|
Grade 4
|
|
Preferred Term
|
N
|
%
|
N
|
%
|
N
|
%
|
|
aStomatitis or mucosal inflammation of the gastrointestinal and genitourinary tracts.
|
|
bFive patients with platelets < 10,000/μL
|
|
cAlanine aminotransferase, aspartate aminotransferase, and transaminases increased
|
| Any Adverse Event
|
111
|
100
|
48
|
43
|
34
|
31
|
| Mucositisa
|
78
|
70
|
19
|
17
|
4
|
4
|
| Thrombocytopeniab
|
45
|
41
|
15
|
14
|
21
|
19b
|
| Nausea
|
44
|
40
|
4
|
4
|
0
|
0
|
| Fatigue
|
40
|
36
|
5
|
5
|
2
|
2
|
| Anemia
|
38
|
34
|
17
|
15
|
2
|
2
|
| Constipation
|
37
|
33
|
0
|
0
|
0
|
0
|
| Pyrexia
|
36
|
32
|
1
|
1
|
1
|
1
|
| Edema
|
33
|
30
|
1
|
1
|
0
|
0
|
| Cough
|
31
|
28
|
1
|
1
|
0
|
0
|
| Epistaxis
|
29
|
26
|
0
|
0
|
0
|
0
|
| Vomiting
|
28
|
25
|
2
|
2
|
0
|
0
|
| Neutropenia
|
27
|
24
|
14
|
13
|
8
|
7
|
| Diarrhea
|
23
|
21
|
2
|
2
|
0
|
0
|
| Dyspnea
|
21
|
19
|
8
|
7
|
0
|
0
|
| Anorexia
|
17
|
15
|
3
|
3
|
0
|
0
|
| Hypokalemia
|
17
|
15
|
4
|
4
|
1
|
1
|
| Rash
|
17
|
15
|
0
|
0
|
0
|
0
|
| Pruritus
|
16
|
14
|
2
|
2
|
0
|
0
|
| Pharyngolaryngeal pain
|
15
|
14
|
1
|
1
|
0
|
0
|
| Liver function test abnormalc
|
14
|
13
|
6
|
5
|
0
|
0
|
| Abdominal pain
|
13
|
12
|
4
|
4
|
0
|
0
|
| Pain in extremity
|
13
|
12
|
0
|
0
|
0
|
0
|
| Back pain
|
12
|
11
|
3
|
3
|
0
|
0
|
| Leukopenia
|
12
|
11
|
3
|
3
|
4
|
4
|
| Night sweats
|
12
|
11
|
0
|
0
|
0
|
0
|
| Asthenia
|
11
|
10
|
1
|
1
|
0
|
0
|
| Tachycardia
|
11
|
10
|
0
|
0
|
0
|
0
|
| Upper respiratory tract infection
|
11
|
10
|
1
|
1
|
0
|
0
|
Serious Adverse Events
Forty-four percent of patients (n = 49) experienced a serious adverse event while on study or within 30 days after their last dose of FOLOTYN. The most common serious adverse events (> 3%), regardless of causality, were pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia. One death from cardiopulmonary arrest in a patient with mucositis and febrile neutropenia was reported in this trial. Deaths from mucositis, febrile neutropenia, sepsis, and pancytopenia occurred in 1.2% of patients treated on all FOLOTYN trials at doses ranging from 30 to 325 mg/m2.
Discontinuations
Twenty-three percent of patients (n = 25) discontinued treatment with FOLOTYN due to adverse reactions. The adverse reactions reported most frequently as the reason for discontinuation of treatment were mucositis (6%, n = 7) and thrombocytopenia (5%, n = 5).
Dose Modifications
The target dose of FOLOTYN was 30 mg/m2 once weekly for 6 weeks in 7-week cycles. The majority of patients (69%, n = 77) remained at the target dose for the duration of treatment. Overall, 85% of scheduled doses were administered.
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