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