Table 2.
Dose adjustment criteria
| NCI CTCAE 5.0 | Management (after active treatment and observation) | Dose adjustment after the study drug is continued |
|---|---|---|
| Pyrotinib | ||
| Clinically significant grade ≥ 2 declined LVEF or LVEF lower than the lower limit of normal (including LVEF declining ≥10% and LVEF < 50% without symptoms, or heart failure) | Discontinue pyrotinib | |
| Grade 4 diarrhea | Discontinue pyrotinib | |
| Grade 3 diarrhea or grade 1–2 diarrhea with concomitant symptoms (including but not limited to mild to severe abdominal cramps, grade ≥ 2 nausea or vomiting, declined ECOG performance status, fever, pyemia, decreased neutrophil count, bleeding or dehydration) | Interrupt pyrotinib until diarrhea is restored to grade 0–1 and concomitant symptoms disappear | 80 mg reduction each time to the minimum dose of 240 mg |
| Grade ≥ 2 non-hematologic AEs (except for alopecia, fatigue and asthenia) | Interrupt pyrotinib until diarrhea is restored to grade 0–1 | 80 mg reduction each time to the minimum dose of 240 mg |
| Grade ≥ 3 hematologic AEs | Interrupt pyrotinib until diarrhea is restored to grade 0–1 | 80 mg reduction each time to the minimum dose of 240 mg |
| Thalidomide | ||
| Constipation, somnolence, or peripheral neuropathy | Consider interrupting thalidomide | Dose can be reduced as per investigator’s discretion |
| Grade 3–4 AEs or clinically significant symptoms | Consider interrupting or discontinuing thalidomide | Dose reduction can be considered |
| Angioedema, allergic reaction, grade 4 rash, skin peeling, bullae, or any other severe skin reaction | Discontinue thalidomide | |
NCI CTCAE National Cancer Institute Common Terminology Criteria for Adverse Events, LVEF left ventricular ejection fraction, ECOG Eastern Cooperative Oncology Group, AE adverse event