Adverse Reactions
- Adverse reactions, regardless of causality, that occurred in at least 10% of patients treated with TARCEVA 100 mg plus gemcitabine in the randomized trial of patients with pancreatic cancer are summarized by NCI-CTC (version 2.0) Grade.1, 2
- The most common adverse reactions in pancreatic cancer patients receiving TARCEVA 100 mg plus gemcitabine were fatigue, rash, nausea, anorexia and diarrhea. In the TARCEVA plus gemcitabine arm, Grade 3/4 rash and diarrhea were each reported in 5% of TARCEVA plus gemcitabine-treated patients. The median time to onset of rash and diarrhea was 10 days and 15 days, respectively. Rash and diarrhea each resulted in dose reductions in 2% of patients, and resulted in study discontinuation in up to 1% of patients receiving TARCEVA plus gemcitabine. The 150 mg cohort was associated with a higher rate of certain class-specific adverse reactions including rash and required more frequent dose reduction or interruption.1, 2
Adverse Reactions Occurring in ≤10% of TARCEVA-treated Pancreatic Cancer Patients: 100 mg cohort*
| TARCEVA +
gemcitabine 1000 mg/m2 IV N=259 |
Placebo +
gemcitabine 1000 mg/m2 IV N=256 |
|||||
| NCI-CTC Grade | Any grade | Grade 3 | Grade 4 | Any grade | Grade 3 | Grade 4 |
| MedDRA Preferred Term | % | % | % | % | % | % |
| Fatigue | 73 | 14 | 2 | 70 | 13 | 2 |
| Rash | 69 | 5 | 0 | 30 | 1 | 0 |
| Nausea | 60 | 7 | 0 | 58 | 7 | 0 |
| Anorexia | 52 | 6 | <1 | 52 | 5 | <1 |
| Diarrhea | 48 | 5 | <1 | 36 | 2 | 0 |
| Abdominal pain | 46 | 9 | <1 | 45 | 12 | <1 |
| Vomiting | 42 | 7 | <1 | 41 | 4 | <1 |
| Weight decreased | 39 | 2 | 0 | 29 | <1 | 0 |
| Infection* | 39 | 13 | 3 | 30 | 9 | 2 |
| Edema | 37 | 3 | <1 | 36 | 2 | <1 |
| Pyrexia | 36 | 3 | 0 | 30 | 4 | 0 |
| Constipation | 31 | 3 | 1 | 34 | 5 | 1 | Bone pain | 25 | 4 | <1 | 23 | 2 | 0 |
| Dyspnea | 24 | 5 | <1 | 23 | 5 | 0 |
| Stomatitis | 22 | <1 | 0 | 12 | 0 | 0 |
| Myalgia | 21 | 1 | 0 | 20 | <1 | 0 |
| Depression | 19 | 2 | 0 | 14 | <1 | 0 |
| Dyspepsia | 17 | <1 | 0 | 13 | <1 | 0 |
| Cough | 16 | 0 | 0 | 11 | 0 | 0 |
| Dizziness | 15 | <1 | 0 | 13 | 0 | <1 |
| Headache | 15 | <1 | 0 | 10 | 0 | 0 |
| Insomnia | 15 | <1 | 0 | 16 | <1 | 0 |
| Alopecia | 14 | 0 | 0 | 11 | 0 | 0 |
| Anxiety | 13 | 1 | 0 | 11 | <1 | 0 |
| Neuropathy | 13 | 1 | <1 | 10 | <1 | 0 |
| Flatulence | 13 | 0 | 0 | 9 | <1 | 0 |
| Rigors | 12 | 0 | 0 | 9 | 0 | 0 |
| * Includes all MedDRA preferred terms in the Infections and Infestations System Organ Class. | ||||||
In the pancreatic carcinoma trial, 10 patients in the TARCEVA/gemcitabine group developed deep venous thrombosis (incidence: 3.9%). In comparison, 3 patients in the placebo/gemcitabine group developed deep venous thrombosis (incidence 1.2%). The overall incidence of grade 3 or 4 thrombotic events, including deep venous thrombosis, was similar in the two treatment arms: 11% for TARCEVA plus gemcitabine and 9% for placebo plus gemcitabine.
No differences in Grade 3 or Grade 4 hematologic laboratory toxicities were detected between the TARCEVA plus gemcitabine group compared to the placebo plus gemcitabine group.
Severe adverse reactions (≥grade 3 NCI-CTC) in the TARCEVA plus gemcitabine group with incidences <5% included syncope, arrhythmias, ileus, pancreatitis, hemolytic anemia including microangiopathic hemolytic anemia with thrombocytopenia, myocardial infarction/ischemia, cerebrovascular accidents including cerebral hemorrhage, and renal insufficiency.
Liver function test abnormalities (including elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin) have been observed following the administration of TARCEVA plus gemcitabine in patients with pancreatic cancer. TARCEVA dosing should be interrupted or discontinued if changes in liver function are severe.
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