A phase ib, open-label study to assess the safety of continuous oral treatment with afatinib in combination with two chemotherapy regimens: Cisplatin plus paclitaxel and cisplatin plus 5-fluorouracil, in patients with advanced solid tumors

Annals of Oncology

Volumn 24, Issue 5, 2013, Pages 1392-1400

  Vermorken, J B ^a   Rottey, S ^b   Ehrnrooth, E ^c   Pelling, K ^d   Lahogue, A ^e   Wind, S ^c   Machiels, J P ^f  

^a ANTWERP UNIVERSITY HOSPITAL   (Belgium)

^b GHENT UNIVERSITY   (Belgium)

^c BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^d BOEHRINGER INGELHEIM LTD   (United Kingdom)

^e Boehringer Ingelheim   (Belgium)

^f CLINIQUES UNIVERSITAIRES SAINT LUC   (Belgium)

Author keywords

Afatinib; Cisplatin; Paclitaxel; Phase Ib

Indexed keywords

AFATINIB; CISPLATIN; FLUOROURACIL; PACLITAXEL;

ADULT; ADULT RESPIRATORY DISTRESS SYNDROME; ADVANCED CANCER; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALOPECIA; ANEMIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ASTHENIA; BLOOD SAMPLING; BLOOD TOXICITY; CANCER CLASSIFICATION; CANCER CONTROL; CLINICAL ARTICLE; COHORT ANALYSIS; CONSTIPATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DECREASED APPETITE; DIARRHEA; DIGESTIVE SYSTEM CANCER; DIZZINESS; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG FATALITY; DRUG FEVER; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; FATIGUE; FEBRILE NEUTROPENIA; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; GASTROINTESTINAL SYMPTOM; GASTROINTESTINAL TOXICITY; GYNECOLOGIC CANCER; HEAD AND NECK CANCER; HEART ATRIUM FIBRILLATION; HUMAN; HYPOKALEMIA; HYPOMAGNESEMIA; HYPONATREMIA; KIDNEY FAILURE; LACTATE DEHYDROGENASE BLOOD LEVEL; LUNG CANCER; LUNG EDEMA; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MUCOSA INFLAMMATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUROLOGIC DISEASE; NEUTROPENIA; OPEN STUDY; OUTCOME ASSESSMENT; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RESPIRATORY DISTRESS SYNDROME; SEPTIC SHOCK; SIDE EFFECT; SKIN CANCER; SOLID TUMOR; STOMATITIS; THROMBOCYTOPENIA; VOMITING;

ADULT; AGED; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CISPLATIN; DRUG ADMINISTRATION SCHEDULE; FLUOROURACIL; HUMANS; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASMS; PACLITAXEL; QUINAZOLINES;

EID: 84877148074     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mds633     Document Type: Article

References (25)

1. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005; 5: 341-354.
2. Salomon DS, Brandt R, Ciardiello F et al. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995; 19: 183-232.
3. Citri A, Yarden Y. EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 2006; 7: 505-516.
4. Li D, Ambrogio L, Shimamura T et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 2008; 27: 4702-4711.
5. Solca F, Dahl G, Zoephel A et al. Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker. J Pharmacol Exp Ther 2012; 342: 342-350.
6. Solca F, Baum A, Guth B et al. BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor for cancer therapy. In AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Philadelphia, PA: 2005.
7. Eskens FA, Mom CH, Planting AS et al. A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours. Br J Cancer 2008; 98: 80-85.
8. Lewis N, Marshall J, Amelsberg A et al. A phase I dose escalation study of BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in a 3 week on 1 week off schedule in patients with advanced solid tumours. J Clin Oncol 2006; 24: S3091.
9. Yap TA, Vidal L, Adam J et al. Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors. J Clin Oncol 2010; 28: 3965-3972.
10. Agus DB, Terlizzi E, Stopfer P et al. A phase I dose escalation study of BIBW 2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in a continuous schedule in patients with advanced solid tumours. J Clin Oncol 2006; 24: 2074.
11. Gibson MK, Li Y, Murphy B et al. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): an intergroup trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2005; 23: 3562-3567.
12. Marshall J, Shapiro GI, Terlizzi E et al. A Phase I dose escalation trial of BIBW 2992, an irreversible EGFR/HER2 kinase inhibitor, for 20 and 13 days in combination with docetaxel every 21 days. Ann Oncol 2008; 19: 474.
13. Awada AH, Dumez H, Wolter P et al. A phase I dose finding study of the 3-day administration of BIBW 2992, an irreversible dual EGFR/HER2 inhibitor, in combination with 3-weekly docetaxel in patients with advanced solid tumors. J Clin Oncol 2009; 27: 15s.
14. Ang JE, Mikropoulos C, Stavridi F et al. A phase I study of daily BIBW 2992, an irreversible EGFR/HER2 dual kinase inhibitor, in combination with weekly paclitaxel. J Clin Oncol 2009; 27: 15s.
15. Therasse P, Arbuck SG, Eisenhauer EA et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000; 92: 205-216.
16. Breidenbach M, Rein DT, Schondorf T et al. Hematological side-effect profiles of individualized chemotherapy regimen for recurrent ovarian cancer. Anticancer Drugs 2003; 14: 341-346.
17. McGuire WP, Blessing JA, Moore D et al. Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study. J Clin Oncol 1996; 14: 792-795.
18. Yap TA, Vidal L, Adam J et al. Phase I trial of the irreversible ErbB1 (EGFR) and ErbB2 (HER2) kinase inhibitor BIBW 2992 in patients with advanced solid tumours. J Clin Oncol 2010; 28: 3965-3972.
19. Grandis JR, Tweardy DJ. Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res 1993; 53: 3579-3584.
20. Normanno N, De Luca A, Bianco C et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006; 366: 2-16.
21. Murakami H, Tamura T, Takahashi T et al. Phase I study of continuous afatinib (BIBW 2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4). Cancer Chemother Pharmacol 2012; 69: 891-899.
22. Miller VA, Hirsh V, Cadranel J et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol 2012; 13: 528-538.
23. Yang JC, Shih JY, Su WC et al. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol 2012; 13: 539-548.
24. Spicer JF, Rudman SM. EGFR inhibitors in non-small cell lung cancer (NSCLC): the emerging role of the dual irreversible EGFR/HER2 inhibitor BIBW 2992. Target Oncol 2010; 5: 245-255.
25. Bei R, Budillon A, Masuelli L et al. Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patients. J Pathol 2004; 204: 317-325.