title: Gemcitabine plus Epi-doxorubicin as first-line chemotherapy for bladder cancer in advanced or metastatic stage: a phase II.
abstract: Combination chemotherapy with newer, more active drugs in patients with advanced and/or metastatic bladder cancer might show improved response rate and survival. Gemcitabine (GEM) and Epidoxorubicin (EPI) have demonstrated activity in this disease. In addition, experimental studies in vitro have shown that the two agents have additive-synergistic effects when used in combination. Our prior phase I dose-finding study in previously untreated patients with advanced or metastatic bladder cancer defined recommended doses for further trials of GEM 1000 mg/m2 and EPI 25 mg/m2 on days 1, 8 and 15 every 28 days. A phase II trial at this dose level was initiated in previously untreated patients to assess efficacy and toxicity. Eligible patients had measurable disease; Karnofsky performance status (PS) of > 40; no prior chemotherapy; and adequate bone marrow reserve, cardiac, hepatic and renal function. Thirty- one patients (22 males, 9 females) with median age of 64 (range 44-75) and median PS of 80 were accrued, and all were eligible. Twelve patients had T4N1-2 M0, 8 had lymph node only metastases, while 11 had visceral metastases (liver, bone, lung). A total of 181 cycles was administered (range 3-7 per patient). Major toxicities (WHO grade > or = 3) were: neutropenia in 5 patients, thrombocytopenia in 2 patients, and anemia in 2 patients. Three patients had febrile neutropenic episodes and only 3 patients required dose reduction. Grade 1-2 non-hematological toxicities included nausea/vomiting, stomatitis and alopecia. No cardiac toxicity was observed. Of the 30 response evaluable patients, 17 (57%) demonstrated a major response (3 complete and 14 partial) (95% CI: 39%-75%), 7 had stable disease (23%) and 6 progressed (20%). These preliminary results confirm the phase I observation that the combination of GEM--EPI is highly active in the treatment of advanced and metastatic bladder cancer with a favourable toxicity profile.
authors.affiliation: Department of Internal Medicine, Oncological Day Hospital, Viale Pieraccini 18, 50139 Florence, Italy. brunoneri@unifi.it
authors.forename: B
authors.initials: B
authors.lastname: Neri
authors.forename: L
authors.initials: L
authors.lastname: Doni
authors.forename: C
authors.initials: C
authors.lastname: Fulignati
authors.forename: M T
authors.initials: MT
authors.lastname: Gemelli
authors.forename: M
authors.initials: M
authors.lastname: Turrini
authors.forename: V
authors.initials: V
authors.lastname: Di Cello
authors.forename: A
authors.initials: A
authors.lastname: Dominici
authors.forename: A
authors.initials: A
authors.lastname: Mottola
authors.forename: A
authors.initials: A
authors.lastname: Raugei
authors.forename: R
authors.initials: R
authors.lastname: Ponchietti
authors.forename: G
authors.initials: G
authors.lastname: Cini
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D015251:Epirubicin; D000093542:Gemcitabine