Characteristics, therapy and outcome in an unselected and prospectively registered cohort of pancreatic cancer patients.

PURPOSE: Pancreatic cancer (PC) is associated with a dismal prognosis. Few studies have examined characteristics and outcome in an unselected population-based cohort of PC patients. Therefore, we investigated patient baseline characteristics, therapy choices and survival in a complete cohort of patients with PC. METHODS: All cases diagnosed with PC between 2007 and 2009 in the Region of Southern Denmark (pop: 1,200,000) were prospectively registered. Patient characteristics including performance status, information about haematology, liver function and therapy were retrieved from patient charts, and used to compare differently treated and untreated groups. RESULTS: Six-hundred-eighteen cases were registered as PC; 25 of which did not have adenocarcinomas. Patients were divided in 3 clinical groups based on initial therapy; group 1: resection (n=64), group 2: chemotherapy or chemo-radiotherapy (n=191), group 3: no tumour directed therapy (n=324). Median survival (mOS) (95% confidence interval (CI)) in the three groups was 25.7 months (18-30), 8.1 months (7.0-9.5) and 1.1 months (1.0-1.3) respectively. Three percent of patients participated in clinical trials. An evaluation of baseline factors prognostic value suggested that treated patients differed significantly from non-treated patients. CONCLUSION: This study reports survival in treated groups comparable to results obtained from clinical trials with highly selected patients. However the majority of patients with PC do not receive cancer directed therapy. This group was significantly different in several baseline factors, which could suggest a different biology. Improving the outcome of PC patients calls for research into the large group of untreated patients, as only a minority of patients receive cancer directed therapy.

Phase II study of biweekly cetuximab in combination with irinotecan as second-line treatment in patients with platinum-resistant gastro-oesophageal cancer.

BACKGROUND: The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma. PATIENTS AND METHODS: Patients with failure to first-line platinum-based chemotherapy received cetuximab 500 mg/m(2) and irinotecan 180 mg/m(2) every second week until disease progression. Toxicity was evaluated according to The Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v. 3.0. Antitumour activity was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST) v. 1.0. RESULTS: Sixty-three patients were enrolled, median age was 60 years, median performance status was 1 (0-1), 35 patients had two or more organs involved. The median number of courses was 5 (range 1-25). Response rate was 11% (6 partial response (PR)) and 37% had stable disease. Median progression free survival was 2.8 months and overall survival (OS) was 6.1 months. Grade 3-4 toxicity included: diarrhoea (6%), fatigue (5%), vomiting (5%) and neutropenia (16%). Two patients developed febrile neutropenia. Forty-six patients (73%) had developed grade 1-2 skin rash. Patients developing skin rash had a prolonged survival with an OS at 7.1 months. CONCLUSIONS: The combination of cetuximab and irinotecan is active as second-line therapy in patients with gastro-oesophageal cancer. Cetuximab induced skin rash was associated with prolonged survival.

Phase II study of short-time oxaliplatin, capecitabine and epirubicin (EXE) as first-line therapy in patients with non-resectable gastric cancer.

Epirubicin, cisplatin and continuous infusion of 5-FU is a widely used palliative regimen in patients with gastric cancer. If cisplatin is substituted by oxaliplatin and 5-FU by capecitabine this regimen can be administered in the outpatient setting. Dose-limiting toxicity of oxaliplatin is peripheral sensory neuropathy and it is recommended to give oxaliplatin as a 120 min infusion. However, in patients with colorectal cancer a 30 min infusion of oxaliplatin can safely be administered without increasing neurotoxicity, standard infusion time is 30 min at our departments. In our phase I study the recommended doses of EXE was established (Dupont et al, 2006). Patients with non-resectable gastric adenocarcinoma were eligible. Patients received EXE (epirubicin 50 mg m(-2) day 1; capecitabine 1000 mg m(-2) day(-1) continuously and oxaliplatin 130 mg m(-2) day 1) as outpatient therapy every third week for a maximum of 8 cycles. From June 2004 to September 2005, we enroled 54 patients. Median age was 60 years (31-74 years) Median number of courses was 6 (1-8). Response rate was 45%. Median PFS was 6.8 (5.2-7.9) months and median survival was 10.1 (7.9-1.1) months. Most important grade 3 toxicities were as follows: nausea, vomiting, and diarrhoea (6%). Neurotoxicity grade 2 was seen in 36.5%. We therefore conclude, that EXE every third week is a convenient regimen that easily can be administrated in the outpatient setting but the regimen needs further evaluation in a phase III study.

Patient preference for oral or intravenous chemotherapy: a randomised cross-over trial comparing capecitabine and Nordic fluorouracil/leucovorin in patients with colorectal cancer.

Until recently, fluorouracil (F) and leucovorin (L) had been considered the standard therapy for patients with colorectal cancer. However, several studies have shown that oral therapy with UFT/L or capecitabine is as effective as intravenous (i.v.) therapy and in addition it is claimed that patients prefer oral to i.v. therapy as long as efficacy is not compromised. In a previous crossover study by Borner et al., it was shown that 26 out of 31 patients preferred oral therapy with UFT/L to i.v. FL (Mayo regimen) [Borner M, Schöffski P, de Wit R, et al. Patient preferences and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur J Cancer 2002;38:349-58]. The objective of the present study was to investigate patient preference between i.v. FL and oral capecitabine using the design described by Borner. The Nordic FL schedule is a bolus regimen with efficacy comparable to other i.v. regimens and at the same time a very tolerable and easy administered regimen. We randomised 60 patients with colorectal cancer (53 patients received adjuvant therapy and seven patients received palliative therapy) to start therapy with either oral capecitabine or Nordic bolus FL. After 6 weeks of therapy (two courses of capecitabine or three courses of Nordic FL) patients were crossed over to the other regimen. After having completed 12 weeks of therapy the patients (49 evaluable patients) were asked to choose one of the regimens for a further 12 weeks of therapy. Patients had more side-effect when treated with capecitabine and a total of 30 out of 49 (61%) preferred the Nordic FL regimen and 19 (39%) preferred capecitabine. We conclude that patients prefer the regimen with less toxicity and that it is of minor importance whether the medication is administrated orally at home or i.v. at the hospital.