000K utf8 1100 $c2014 1500 eng 2050 urn:nbn:de:gbv:8-mods-2020-00555-4 2051 10.1159/000365553 3000 Maass, Nicolai Henning 3010 Alkatout, Ibrahim 3010 Baier, Monika 3010 Bauer, Maret 3010 Bauerschlag, Dirk Olaf 3010 Hanson, Sven 3010 Jonat, Walter 3010 Mundhenke, Christoph 3010 Muth, Mathias 3010 Schaefer, Fritz W 3010 Schem, Christian 3010 Tiemann, Katharina 3010 Weigel, Marion T 3010 Wenners, Antonia S 4000 Final safety and efficacy analysis of a phase I/II trial with imatinib and vinorelbine for patients with metastatic breast cancer [Maass, Nicolai Henning] 4209 BACKGROUND: Imatinib is a tyrosine kinase inhibitor of BCR-ABL, ABL, PDGFR-α and -β, KIT, and DDR. In solid tumors, it inhibits proliferation and invasiveness and facilitates higher intratumoral cytotoxic drug concentrations. Vinorelbine has good tolerability and efficacy in metastatic breast cancer (MBC). This study evaluates the safety and efficacy of imatinib and vinorelbine in combination. METHODS: In a prospective, open-label, phase I/II trial, 400 mg imatinib p.o. daily (corrected from 600 mg) was combined with an escalating dose of vinorelbine i.v. weekly in four dose levels of 10, 15, 20, and 25 mg/m(2) (each n ≥ 5) to treat patients with MBC (expressing PDGFR-α and/or -β, and/or KIT). The last patient of each level was treated for >28 days, before enrolment for the next dose level started. Study endpoints were feasibility and tolerability, incidence of hematological and nonhematological toxicity, and clinical efficacy (data cutoff: November 18, 2011). A total of 33 patients have been enrolled, and all dose levels have been fully recruited. One patient is still on study medication. A translational subprotocol is ongoing. RESULTS: All 33 included patients are evaluable for safety (32 within the ITT population). Eleven patients were excluded early from the study (progressive disease, toxicity, and withdrawal of consent). Twenty-two patients participated in the study for >28 days ('ITT >28'). Within the ITT population, the response rate [complete response (CR) and partial response (PR)] was 9.4% (n = 3), the clinical benefit rate (CBR; CR+PR+stable disease) 50% (n = 16), and the median time to progression (TTP) 155 days. A total of 21.3% of the patients were on study medication for >6 months, and 15.2% for >12 months (mean 140 days, range 15-643). Within 'ITT >28', the response rate was 13.6%, CBR 72.7%, and median TTP 176 days. The response was independent of the receptor status (PDGFR-α, -β, and KIT). Toxicities were as follows (safety population): 21.6% severe leukopenia, 9.1% severe neutropenia (with 1 febrile neutropenia), 1 case of bowel perforation, 36% diarrhea (3% severe), 84.8% nausea (severe 15.2%), 48.5% vomiting (severe 9.1%), 27.3% infections (severe 6.1%), 12.1% peripheral neuropathy (severe 9.1%), and 36.4% dyspnea (3% severe). Four patients on trial died (nondrug-related). CONCLUSION: The combination of imatinib and vinorelbine in MBC appeared to be feasible and tolerable. A CBR of 50% (ITT) in pretreated patients suggests that this combination may be active. Although toxicities were frequent, they appeared to be manageable. 4950 https://doi.org/10.1159/000365553$xR$3Volltext$534 4950 https://nbn-resolving.org/urn:nbn:de:gbv:8-mods-2020-00555-4$xR$3Volltext$534 4961 https://macau.uni-kiel.de/receive/macau_mods_00000329 5051 610 5550 Adult 5550 Aged 5550 Antineoplastic Combined Chemotherapy Protocols 5550 Benzamides 5550 Breast Neoplasms 5550 Female 5550 Humans 5550 Middle Aged 5550 Neoplasm Metastasis 5550 Piperazines 5550 Prospective Studies 5550 Pyrimidines 5550 Vinblastine