P-0107 Gemcitabine and Cisplatin Combined with Regional Hyperthermia as Second-Line Treatment in Patients with Gemcitabine-Refractory Advanced Pancreatic Cancer

Abstract

IntroductionGemcitabine (G) is the standard first-line treatment in patients with advanced pancreatic cancer (APC). Currently there is no standard second-line therapy for patients after G-failure. Cisplatin (Cis)-based chemotherapy has shown activity in APC. From preclinical research it is proven that cytotoxicity of G and Cis is enhanced by heat exposure at 40° to 42°C. Here we show first clinical data on the combination of G plus Cis with regional hyperthermia (RHT; 40° to 42°C) as second-line treatment in APC patients with G-refractory disease. MethodsWe retrospectively analyzed 23 patients with advanced (n=2) or metastatic (n=21) pancreatic cancer with relapse after G mono (n=23) first-line chemotherapy (time to first progression; TTP1). Patients had received G (day1, 1000mg/m2) and Cis (day 2 and 4, 25mg/m2) in combination with RHT (day 2 and 4, 1 hour) using the BSD 2000 system. A total of 8 cycles including 16 RHT applications was prescribed in a biweekly schedule. The treatment protocol was approved by the local ethics committee (project number 79/98) and signed informed consent was received from each patient before start of therapy. We analyzed feasibility and toxicity, addressing both hematological and non-hematological side effects according to NCI criteria. Time to second progression (TTP2) and overall survival (OS) was analyzed for all patients. Clinical response according to RECIST criteria was assessed for patients with available CT scans. ResultsBetween 10/99 and 08/08 23 pts were treated and received a median of 5 [range 1-12] chemotherapy cycles and 6.5 [range 1-16] hyperthermia treatments. Hematological toxicity was low with no grade 4 event, but grade 3 anemia and leukopenia in six and three patients. Hyperthermia-associated toxicity consisted of discomfort because of bolus pressure (3%), power-related pain (7%) or position-related pain (17%), with a total of 6 break ups (3%) of hyperthermia sessions in 5 patients. Median TTP1 was 5.9 months (95% CI: 2.6-9.2), median TTP2 was 4.3 months (95% CI: 1.2-7.4) and OS 12.9 months (95% CI: 9.9-15.9). The disease control rate in 16 patients with available CT scans was 50% (1 PR, 7 SD, 8 PD). ConclusionWe show first clinical data that G plus Cis combined with RHT is clinically active in G-pre-treated advanced pancreatic cancer with low toxicity. A prospective controlled phase II clinical trial of G+CIS+RHT (EudraCT: 2005-003855-11) using this setting is currently open for recruitment.