When events were noted as both all grade and grade 3-5 adverse drug reactions in clinical trials, the highest frequency observed in patients has been reported. Data are unadjusted for the differential time on treatment.

a For further information please refer to Table 3 'Adverse reactions reported in post-marketing setting.'

b Terms represent a group of events that describe a medical concept rather than a single condition or MedDRA (Medical Dictionary for Regulatory Activities) preferred term. This group of medical terms may involve the same underlying pathophysiology (e.g. arterial thromboembolic reactions include cerebrovascular accident, myocardial infarction, transient ischaemic attack and other arterial thromboembolic reactions).

c Based on a substudy from NSABP C-08 with 295 patients

d For additional information refer below within section "Further information on selected serious adverse reactions."

e Recto-vaginal fistulae are the most common fistulae in the GI-vaginal fistula category.

f Observed in pediatric population only

Table 2: Severe Adverse Reactions by Frequency

System organ class
 Very Common
 Common
 Uncommon
 Rare
 Very Rare
 Frequency Not Known
 
 Infections and infestations
   Sepsis, Cellulitis, Abscessa,b, Infection, Urinary tract infection
       Necrotising fasciitisc
 
Blood and lymphatic system disorders
 Febrile neutropenia, Leucopenia, Neutropeniaa, Thrombo-cytopenia
 Anaemia, Lymphopenia
        
Immune system disorders
           Hypersensitivity, infusion reactions a,b,c
 
Metabolism and nutrition disorders
   Dehydration
        
Nervous system disorders
 Peripheral sensory neuropathya
 Cerebrovascular accident, Syncope, Somnolence, Headache
       Posterior reversible encephalopathy syndrome a,b,c, Hypertensive encephalopathyc
 
Cardiac disorders
   Congestive heart failurea,b, Supraventricular tachycardia
        
 Vascular disorders
 Hypertensiona,b
  Thromboembolism arteriala,b, Haemorrhagea,b, Thromboembolism (venous)a,b

Deep vein thrombosis
        Renal thrombotic microangiopathyb,c
 
Respiratory, thoracic and mediastinal disorders
   Pulmonary haemorrhage/ Haemoptysisa,b, Pulmonary embolism, Epistaxis, Dyspnoea, Hypoxia
       Pulmonary hypertensionc, Nasal septum perforationc
 
Gastroint