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Table 1 Protocol-defined dose modifications for etirinotecan pegol in subsequent cycles based on worst toxicity in prior cycle

From: Safety and tolerability of etirinotecan pegol in advanced breast cancer: analysis of the randomized, phase 3 BEACON trial

Adverse event by NCI CTCAE grade Dose modification
Hematologic (thrombocytopenia, anemia, neutropenia, febrile neutropenia)
 Grade 1–2 (except ANC) Maintain dose level
 Grade 2 (ANC <1500/mm3) First occurrence
  • Hold until ANC >1500/mm3
  • If screening ANC >2000/mm3; restart at reduced dose of 120 mg/m2
  • Do not dose reduce if screening ANC was ≥1500 but <2000/mm3
  Second occurrence
  • Decrease one dose level (to 90 or 120 mg/m2)
  Third occurrence
  • Discontinue treatment
 Grade 3 (platelets <50 K or Hgb <8 g/dl) First occurrence
  • Hold until resolved; restart at 120 mg/m2
  Second occurrence
  • Decrease additional dose level to 90 mg/m2
  Third occurrence
  • Discontinue treatment
 Grade 4 (ANC <500/mm3 or platelets <25 K or Hgb <6.5 g/dl) First occurrence
  • Hold until resolved (ANC >1500/mm3; Hgb >8 g/dl; platelets >50 K)
  • Restart at reduced dose of 120 mg/m2
  Second occurrence
  • Decrease additional dose level to 90 mg/m2
  Third occurrence
  • Discontinue treatment
 Febrile neutropenia (grade 3: ANC <1000/mm3 with a single temperature >38.3 °C or a sustained temperature of ≥38 °C for more than 1 h) First occurrence
  • Hold until resolved until grade 0–1 toxicity
  • Restart at reduced dose of 120 mg/m2
  Second occurrence
  • Decrease additional dose level to 90 mg/m2
  Third occurrence
  • Discontinue treatment
Diarrhea
 All grades Confirm that diarrhea has been resolved for at least 7 days without use of supportive care prior to retreatment
 Grade 1 Maintain dose level; consider prophylactic anti-diarrheal supportive care
 Grade 2 First occurrence
  • Decrease one dose level to 120 mg/m2
  • Consider prophylactic anti-diarrheal supportive care
  Second occurrence
  • Decrease additional dose level to 90 mg/m2
  Third occurrence
  • Discontinue treatment
 Grade 3–4 First occurrence:
  • Decrease two dose levels to 90 mg/m2
  • Use prophylactic anti-diarrheal supportive care
  Second occurrence
  • Provided that adequate supportive care was given previously, discontinue treatment
  • If the patient did not receive adequate prior supportive care, retreatment may be attempted if 2nd episode of grade 3 diarrhea
  • Discontinue treatment for 2nd episode of grade 4 diarrhea
Dehydration
 Grade 1 • Maintain dose level and consider appropriate prophylactic anti-emetic or anti-diarrheal supportive care
 Grade 2 • Maintain dose level or decrease to 120 mg/m2 after first occurrence; consider appropriate prophylactic anti-emetic or anti-diarrheal supportive care
  • Decrease one dose level (to 120 or 90 mg/m2) after second occurrence; use appropriate prophylactic anti-emetic or anti-diarrheal supportive care
  • Up to two dose reductions are allowed
 Grade 3–4 • Delay treatment until resolution to baseline or to grade 0
  • Decrease dose level to 90 mg/m2 after first occurrence; use appropriate prophylactic anti-emetic or anti-diarrheal supportive care
  • Discontinue after 2nd occurrence
Nausea/vomiting/abdominal pain
 Grade 1–2 • Maintain dose level and consider prophylactic anti-emetic supportive care
 Grade 3 • Delay treatment until resolution to baseline or to grade 0
  • Decrease one dose level to 120 mg/m2 after first occurrence and use prophylactic anti-emetic supportive care
  • Decrease an additional dose level to 90 mg/m2 after second occurrence
  • Discontinue treatment after third occurrence
 Grade 4 • Delay treatment until resolution to baseline or to grade 0
  • Decrease dose level to 90 mg/m2 after first occurrence and use prophylactic anti-emetic supportive care
  • Discontinue treatment after second occurrence