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. Author manuscript; available in PMC: 2012 Sep 14.
Published in final edited form as: JAMA. 2012 Apr 4;307(13):1383–1393. doi: 10.1001/jama.2012.385

Table 3.

Grade ≥3 Adverse Events by Treatment Within the Wild-Type KRAS Patient Groupa

No. (%) of Patients
mFOLFOX6 (n = 894)
mFOLFOX6 + Cetuximab (n = 931)
Adverse Eventsb Grade 3 Grade 4 Grade 5 Grade 3 Grade 4 Grade 5 P Valuec
Overall 321 (35.9) 132 (14.8) 4 (0.4) 504 (54.1) 168 (18.0) 10 (1.1) <.001

Hypersensitivity allergy 21 (2.3) 2 (0.2) 0 47 (5.0) 9 (1.0) 0 <.001

Cardiovascular
   Thrombosis 18 (2.0) 15 (1.7) 1 (0.1) 19 (2.0) 14 (1.5) 1 (0.1) .86

   Infarction 2 (0.2) 2 (0.2) 1 (0.1) 5 (0.5) 4 (0.4) 0 .32

Constitutional symptoms
   Fatigue 38 (4.3) 0 0 58 (6.2) 2 (0.2) 0 .04

   Weight loss 1 (0.1) 0 0 7 (0.8) 0 0 .07d

Acne/rash 3 (0.3) 0 0 184 (19.8) 2 (0.2) 0 <.001d

Gastrointestinal
   Diarrhea 75 (8.4) 8 (0.9) 0 145 (15.6) 3 (0.3) 0 <.001

   Stomatitis/mucositis 16 (1.8) 0 0 59 (6.3) 0 0 <.001

   Nausea 32 (3.6) 0 0 40 (4.3) 1 (0.1) 0 .37

   Vomiting 25 (2.8) 2 (0.2) 0 29 (3.1) 0 0 .91

   Anorexia 9 (1.0) 0 0 25 (2.7) 1 (0.1) 0 .005

Neutropenia 2 (0.2) 87 (9.7) 0 5 (0.5) 105 (11.3) 0 .20

Infection 23 (2.6) 5 (0.6) 0 60 (6.4) 4 (0.4) 4 (0.4) <.001

Febrile neutropenia 11 (1.2) 0 0 18 (1.9) 5 (0.5) 0 .05

Pneumonia 6 (0.7) 0 0 3 (0.3) 1 (0.1) 1 (0.1) .71

Hypomagnesemia 2 (0.2) 1 (0.1) 0 16 (1.7) 4 (0.4) 0 <.001d

Paresthesias 135 (15.1) 3 (0.3) 0 130 (14.0) 3 (0.3) 0 .49

Pulmonary
   Dyspnea 5 (0.6) 1 (0.1) 0 24 (2.6) 3 (0.3) 0 <.001

   Pneumonitis 3 (0.3) 2 (0.2) 0 3 (0.3) 2 (0.2) 1 (0.1) .81

Abbreviation: mFOLFOX6, the modified sixth version of the leucovorin, fluorouracil, and oxaliplatin regimen.

a

Patients with wild-type KRAS treated with mFOLFOX6 having grade 3, grade 4, and grade 5 of any classification was 35.9%, 14.8%, and 0.4%, respectively. Addition of cetuximab for these patients resulted in grade 3, grade 4, and grade 5 toxicity rates of 54.1%, 18%, and 1.1%, respectively. During all adverse events experienced, the rate of toxicity of grade 3 or higher was significantly higher for patients with wild-type KRAS treated with cetuximab (2-sided χ2 test, P<.01). Fisher exact test used with at least 1 of the cells in a 2×2 table was less than 5%.

b

Based on National Cancer Institute, Common Toxicity Criteria, version 3.0.11 Calculated as the maximum severity over all cycles of treatment. Acne/rash includes acne not otherwise specified, rash/desquamation, rash, skin irritation, and rash acneiform. Stomatitis/mucositis includes oral cavity, small bowel, and pharynx. Infection is all infections except pneunomia and febrile neutropenia. Peripheral neuropathy is included in paresthesias.

c

Two-sided χ2 test comparing the rate of grade 3 or higher by treatment.

d

By Fisher exact test.

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