Phase I study of pulsatile 3-day administration of afatinib (BIBW 2992) in combination with docetaxel in advanced solid tumors.

Abstract

BACKGROUND:

A phase I study to assess the maximum tolerated dose (MTD) of a short course of afatinib in combination with docetaxel for the treatment of solid tumors.

METHODS:

Patients with advanced solid malignancies received docetaxel 75 mg/m(2) intravenously on day 1 and oral afatinib once daily on days 2-4, in 3-week treatment cycles. The afatinib dose was escalated in successive cohorts of 3-6 patients until dose-limiting toxicity (DLT). The MTD cohort was expanded to 13 patients. Pharmacokinetic parameters were assessed.

RESULTS:

Forty patients were treated. Afatinib doses were escalated to 160 mg/day in combination with 75 mg/m(2) docetaxel. Three patients had drug-related DLTs during cycle 1. The MTD was defined as 90 mg/day afatinib (days 2-4) with docetaxel 75 mg/m(2). The most frequent drug-related adverse events (all grades) were alopecia, diarrhea, stomatitis (all 50 %) and rash (40 %, all grade ≤ 2). Three patients had confirmed responses, two patients had unconfirmed responses and nine patients had durable stable disease >6 cycles. No pharmacokinetic interaction was observed.

CONCLUSION:

Afatinib 90 mg administered for 3 days after docetaxel 75 mg/m(2) is the MTD for this treatment schedule and the recommended phase II/phase III dose. This combination showed anti-tumor activity in phase I, with a manageable adverse-event profile.

• Authors: A H Awada, H Dumez, A Hendlisz, P Wolter, T Besse-Hammer, M Uttenreuther-Fischer, P Stopfer, F Fleischer, M Piccart, P Schöffski
• Journal: Investigational new drugs (Invest New Drugs) Vol. 31 Issue 3 Pg. 734-41 (Jun 2013) ISSN: 1573-0646 [Electronic] United States
• PMID: 23161334 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Quinazolines
• Taxoids
• Docetaxel
• Afatinib

Topics

• Adult
• Afatinib
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, pharmacokinetics)
• Docetaxel
• Drug Administration Schedule
• Female
• Gastrointestinal Diseases (chemically induced)
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasms (blood, drug therapy)
• Quinazolines (administration & dosage, adverse effects, pharmacokinetics)
• Skin Diseases (chemically induced)
• Taxoids (administration & dosage, adverse effects, pharmacokinetics)