title: Triple combination of bevacizumab, gemcitabine and platinum salt in metastatic collecting duct carcinoma.
abstract: BACKGROUND
  Collecting duct carcinoma (CDC) is a rare and aggressive subtype of kidney cancer that responds to platinum-based chemotherapy. Recent phase II trials have established enhanced antitumor activity on combining bevacizumab with chemotherapy in patients with metastatic urothelial carcinoma, a tumor that shares many features with CDC. Our aim was to investigate whether combining bevacizumab with platinum-based chemotherapy might not also show promise in metastatic CDC (mCDC) patients.
  
  
  METHODS
  Five previously untreated patients diagnosed with mCDC received bevacizumab (15 mg/kg) in combination with gemcitabine (1250 mg/m(2), D1-D8) and platinum salt (cisplatin 80 mg/m(2) or carboplatin AUC 5 mg/ml/min) every 3 weeks for up to six cycles. This was followed by bevacizumab maintenance therapy (15 mg/kg).
  
  
  RESULTS
  All five patients (median age, 62 years; range 45-66 years) had an Eastern Cooperative Oncology Group PS of 0-1. They received the triple-drug combination for a median of four cycles (range, 2-6) and bevacizumab maintenance therapy for a median of three cycles (range, 0-17). There were three cases of partial response, one case of stable disease (20 months) and one case of complete remission after surgery of the only metastatic site. Median progression-free survival (PFS) was 15.1 months [95% confidence interval (CI) 5.6-20.4]. Median overall survival (OS) was 27.8 months (95% CI 12.4-unreached). Grades 3 or 4 adverse events were pulmonary embolism (n = 2), neutropenia (n = 2), thrombopenia (n = 1), asthenia (n = 1) and hypertension (n = 1).
  
  
  CONCLUSIONS
  The addition of bevacizumab to platinum-based chemotherapy resulted in a longer PFS and longer OS than recorded in an earlier clinical trial of platinum-based chemotherapy alone. The triple combination was manageable. The French Collaborative Group (Groupe d'Etudes des Tumeurs Uro-Génitales) is planning a prospective multicenter phase II clinical trial of the triple combination in mCDC patients.
  
  
  BACKGROUND
  BEVABEL/MO28644 (EudraCT: 2013-001179-19).
authors.affiliation: Department of Medical Oncology, Hôpital Européen Georges Pompidou, Paris.
authors.forename: N
authors.initials: N
authors.lastname: Pécuchet
authors.forename: F
authors.initials: F
authors.lastname: Bigot
authors.forename: J
authors.initials: J
authors.lastname: Gachet
authors.forename: C
authors.initials: C
authors.lastname: Massard
authors.forename: L
authors.initials: L
authors.lastname: Albiges
authors.forename: C
authors.initials: C
authors.lastname: Teghom
authors.forename: Y
authors.initials: Y
authors.lastname: Allory
authors.forename: A
authors.initials: A
authors.lastname: Méjean
authors.forename: B
authors.initials: B
authors.lastname: Escudier
authors.forename: S
authors.initials: S
authors.lastname: Oudard
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D060046:Maintenance Chemotherapy; D008875:Middle Aged; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D016190:Carboplatin; D002945:Cisplatin; D000093542:Gemcitabine
keywords: bevacizumab; carboplatin; cisplatin; collecting duct carcinoma; gemcitabine