s 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 eva luated 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.
6.2 Post Marketing Experience
Toxic epidermal necrolysis has been identified during post approval use of FOLOTYN. 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 [see Warnings and Precautions (5.3)].
7 DRUG INTERACTIO
