Randomized Phase II trial of nintedanib, afatinib and sequential combination in castration-resistant prostate cancer.

Abstract

AIMS:

The aim of this article was to evaluate afatinib (BIBW 2992), an ErbB family blocker, and nintedanib (BIBF 1120), a triple angiokinase inhibitor, in castration-resistant prostate cancer patients.

PATIENTS & METHODS:

Patients were randomized to receive nintedanib (250 mg twice daily), afatinib (40 mg once daily [q.d.]), or alternating sequential 7-day nintedanib (250 mg twice daily) and afatinib (70 mg q.d. [Combi70]), which was reduced to 40 mg q.d. (Combi40) due to adverse events. The primary end point was progression-free rate at 12 weeks.

RESULTS:

Of the 85 patients treated 46, 20, 16 and three received nintedanib, afatinib, Combi40 and Combi70, respectively. At 12 weeks, the progression-free rate was 26% (seven out of 27 patients) for nintedanib, and 0% for afatinib and Combi40 groups. Two patients had a ≥50% decline in PSA (nintedanib and the Combi40 groups). The most common drug-related adverse events were diarrhea, nausea, vomiting and lethargy.

CONCLUSION:

Nintedanib and/or afatinib demonstrated limited anti-tumor activity in unselected advanced castration-resistant prostate cancer patients.

• Authors: L Rhoda Molife, Aurelius Omlin, Rob J Jones, Vasilios Karavasilis, David Bloomfield, Graeme Lumsden, Peter C Fong, David Olmos, Joe M O'Sullivan, Ian Pedley, Tamas Hickish, Peter Jenkins, Emilda Thompson, Nikhil Oommen, Duncan Wheatley, Catherine Heath, Graham Temple, Katy Pelling, Johann S de Bono
• Journal: Future oncology (London, England) (Future Oncol) Vol. 10 Issue 2 Pg. 219-31 (Feb 2014) ISSN: 1744-8301 [Electronic] England
• PMID: 24490608 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Indoles
• Quinazolines
• Afatinib
• nintedanib

Topics

• Afatinib
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Humans
• Indoles (administration & dosage)
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Metastasis
• Neoplasm Staging
• Prostatic Neoplasms, Castration-Resistant (drug therapy, pathology)
• Quinazolines (administration & dosage)
• Treatment Outcome