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| |  Cisplatin Plus Gemcitabine Provides Significant Survival Benefit Over Gemcitabine Alone in Metastatic Biliary Tract Cancer: Presented at ECCO-ESMO By Chris Berrie BERLIN -- September 24, 2009 -- Combination of cisplatin with gemcitabine (GemCis) provides the first significant survival benefit over gemcitabine alone (Gem) with no clinically significant toxicity in patients with advanced or metastatic biliary tract cancer (ABC), according to a study presented here at the joint 15th Congress of the European Cancer Organisation (ECCO) and 34th Congress of the European Society for Medical Oncology (ESMO). Although biliary tract cancers represent only 3% of gastrointestinal cancers globally, they are the second most common primary hepatic tumour, and, at present, surgery offers the only chance of cure. However, as John Bridgewater, MD, Medial Oncology, Royal Free Hospital, and University College London Medical School, London, United Kingdom, indicated on September 23, “Most patients are inoperable, and disease progression following surgery is common; the all-comers 5-year survival is between 5% to 10%.” Although there is no standard of care for treatment of patients with inoperable ABC, gemcitabine has been documented as having activity, and cisplatin has shown preclinical and clinical synergy with gemcitabine in other tumour types. The randomised phase 2 UK ABC-01 study established improved progression-free survival (PFS) for GemCis over Gem. These 86 patients then went forward into the multicentre, randomised, prospective, phase 3 UK ABC-02 study. A total of 410 patients were randomised to gemcitabine 1,000 mg/m2 on days 1, 8, and 15, every 28 days, for 6 cycles totalling 24 weeks (n = 206) or gemcitabine 1,000 mg/m2 combined with cisplatin 25 mg/m2 only on days 1 and 8, every 21 days, for 8 cycles, totalling 24 weeks (n = 204). All patients had confirmed nonresectable or recurrent/metastatic cholangiocarcinoma, gall bladder, or ampullary carcinoma, with adequate biliary drainage. “The patients were not required to have measurable disease at study entry,” Dr. Bridgewater noted. Patient baseline characteristics were similar between groups. The primary endpoint was overall survival (OS) according to intention-to-treat analysis, with secondary endpoints of PFS, toxicity, and quality of life. OS showed a significant increase for GemCis over Gem, from 8.1 months to 11.7 months (P < .001). Similarly, PFS significantly increased from 5 to 8 months (P < .001). The radiological response of the assessable patients (69%, 79%, respectively) also showed significant benefit for GemCis over Gem, with overall response rates of 71.8% versus 81.4% (P = .049). “Cisplatin also increases duration of treatment, from 14 to 21 weeks [P = .003], and this is almost certainly because of improved disease control in the GemCis cohort,” added Dr. Bridgewater. Cisplatin significantly increased the incidence of grade 3/4 neutropenia from 16% to 25% (P = .034). “This is, however, not translated into episodes of neutropenia in sepsis,” Dr. Bridgewater stressed. With liver function worse in the Gem arm (27.1% vs 16.7%; P = .012), overall, there was no worsening of the quality of life for the addition of cisplatin to gemcitabine. Thus, while noting that this is the first demonstration of a survival benefit from any treatment in ABC, Dr. Bridgewater added, “GemCis is recommended as a worldwide standard of care, and the backbone for future studies.” Funding for this study was provided by Lilly Oncology. [Presentation title: Gemcitabine With or Without Cisplatin in Patients (pts) With Advanced or Metastatic Biliary Tract Cancer (ABC): Final Results of a Multicentre, Randomised Phase 3 Trial (the UK ABC-02 trial). Abstract 6500]
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