title: Dose-finding trial of a combined regimen with bevacizumab, immunotherapy, and chemotherapy in patients with metastatic renal cell cancer: An Italian Oncology Group for Clinical Research (GOIRC) study.
abstract: The aim of this study was to look for the maximum tolerated dose (MTD) of gemcitabine and 5-fluorouracil in a new regimen also containing the antiangiogenic bevacizumab and immunotherapy (IT) for the treatment of metastatic renal cell cancer. The primary objective of this multicenter dose-finding study was to establish the MTD of chemotherapy (CT) in combination with fixed doses of IT and bevacizumab. The secondary objective was to assess the combination's activity. Five escalated dose levels of CT with intravenous gemcitabine and 5-fluorouracil (days 1 and 8 every 28 d), were associated together with intravenous bevacizumab (10 mg/kg on days 1 and 15 every 28 d), subcutaneous interleukin-2 (1 MIU/m² bid on days 8, 9, 15, 16, and 1 MIU/m²/d on days 10-12 and 17-19), and interferon-α-2a (3 MIU on days 10, 12, 17, 19). Of the 27 enrolled patients, 59% had been pretreated. The MTD was not reached. The highest CT dose studied was gemcitabine 1000 mg/m² and 5-fluorouracil 600 mg/m². More frequent grade 3 to 4 toxicities included neutropenia (63%), thrombocytopenia (33%), and fever (26%). The response rate was 33% according to the Response Evaluation Criteria in Solid Tumors. This is the first study that explored the feasibility and safety of combined bevacizumab, IT, and CT in metastatic renal cell cancer. The activity of this regimen is interesting and its efficacy warrants further trials.
authors.affiliation: Azienda Istituti Ospitaleri, Cremona, Italy. sebabuti@libero.it
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Buti
authors.forename: Silvia
authors.initials: S
authors.lastname: Lazzarelli
authors.forename: Matteo Dalla
authors.initials: MD
authors.lastname: Chiesa
authors.forename: Cecilia
authors.initials: C
authors.lastname: Simonelli
authors.forename: Giovanni Lo
authors.initials: GL
authors.lastname: Re
authors.forename: Arvin
authors.initials: A
authors.lastname: Lheshi
authors.forename: Spazzapan
authors.initials: S
authors.lastname: Simon
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Mattioli
authors.forename: Caterina
authors.initials: C
authors.lastname: Caminiti
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Mazza
authors.forename: Maddalena
authors.initials: M
authors.lastname: Donini
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Passalacqua
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy; D057194:Intention to Treat Analysis; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D007558:Italy; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008495:Medical Oncology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016898:Interferon-alpha; D007376:Interleukin-2; D003841:Deoxycytidine; D000068258:Bevacizumab; D005472:Fluorouracil; D000093542:Gemcitabine