Nintedanib and Weekly Docetaxel in Lung Adenocarcinoma

Maximum tolerated dose (MTD) of nintedanib administered in combination with docetaxel. The MTD was defined as the highest dose combination studied for which the incidence of DLTs was no more than 1 out of 6 subjects experiencing a DLT during the first treatment cycle i.e. the incidence of DLTs was no more than 17%. In case dose escalation reached dose level 3 (200 mg bid nintedanib administered without interruption on days of docetaxel infusion) and no more than 1 out of 6 subjects experienced a DLT during the first 28-day cycle at this dose level, dose level 3 was considered the MTD.

Number of participants with DLT occurring during the first treatment cycle. DLT was defined as any of the following adverse events related to nintedanib:

• Non-haematological drug-related Common Terminology Criteria for AEs (CTCAE) grade 3 or greater
• diarrhoea CTCAE grade 2 for >7 days despite supportive care
• nausea CTCAE grade 3 or greater despite supportive care
• vomiting CTCAE grade 2 or greater despite supportive care
• increase in Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) to CTCAE grade 3 or greater
• A increase in ALT and/or AST to CTCAE grade 2 or greater in conjunction with
• total bilirubin increase of CTCAE grade 1 or greater
• Platelets <50 000/mm3 with bleeding (CTCAE ≥3)
• neutropenia of any grade or duration accompanied by fever >38.5°C
• neutropenia grade 4 without fever of >7 days duration
• Inability to resume nintedanib dosing within 21 days after stopping due to toxicity.