title: Efficacy and tolerability of concurrent weekly low dose cisplatin during radiation treatment of localised muscle invasive bladder transitional cell carcinoma: a report of two sequential Phase II studies from the Trans Tasman Radiation Oncology Group.
abstract: OBJECTIVE
  To determine the feasibility, toxicity, and clinical effectiveness of concurrent weekly cisplatin chemotherapy in conjunction with definitive radiation in the treatment of localised muscle invasive bladder cancer.
  
  
  METHODS
  In January 1997 the Trans Tasman Radiation Oncology Group embarked on a Phase II study (TROG 97.01) of weekly cisplatin (35 mg/m(2) x 7 doses) plus radiation to a dose of 63 Gy over 7 weeks. Following an interim toxicity analysis, the dose intensity of cisplatin was reduced to 6 cycles and the radiation schedule changed to 64 Gy over 6.5 weeks leading to the second study (TROG 99.06). A total of 113 patients were enrolled.
  
  
  RESULTS
  Acute grade 3 urinary toxicity occurred in 23% of the patients. Acute grade 4 pelvic toxicity was not seen. Thirty-eight patients (33%) experienced grade 3 or 4 cisplatin related toxicities with 15 patients (12%) requiring significant dose modification. The reduced dose intensity in Study 99.06 improved tolerability. Incidence of significant late morbidity was low (6%). Seventy-nine patients (70%) achieved complete remission at the 6 month cystoscopic assessment. Local invasive recurrence was seen in 11 of the 79 patients (14%). In 18 patients (16%) isolated superficial TCC/CIS were detected (6 months and beyond). The local control rate was 45% with a functional bladder being retained in 69 of the 113 patients (61%). RFS and DSS at 5 years were 33% and 50%, respectively.
  
  
  CONCLUSIONS
  Our two sequential Phase II studies have shown that concurrent chemoradiation using weekly cisplatin in the management of localised invasive bladder TCC is feasible and reasonably well tolerated. This approach is currently being investigated further in a randomised study.
authors.affiliation: Mater Radiation Oncology Centre, Princess Alexandra Hospital, Brisbane, Qld, Australia. Kumar_gogna@health.qld.gov.au
authors.forename: Nirdosh Kumar
authors.initials: NK
authors.lastname: Gogna
authors.forename: John H L
authors.initials: JH
authors.lastname: Matthews
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Turner
authors.forename: Hedy
authors.initials: H
authors.lastname: Mameghan
authors.forename: Heidi
authors.initials: H
authors.lastname: Mameghan
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Duchesne
authors.forename: Nigel
authors.initials: N
authors.lastname: Spry
authors.forename: Martin P
authors.initials: MP
authors.lastname: Berry
authors.forename: Jacqui
authors.initials: J
authors.lastname: Keller
authors.forename: Lee
authors.initials: L
authors.lastname: Tripcony
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods; D015653:Cystectomy; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin