13-cis-retinoic acid in combination with gemcitabine in the treatment of locally advanced and metastatic pancreatic cancer -: Report of a pilot phase II study

Aims: Adenocarcinoma of the pancreas is a cancer with extremely poor prognosis and limited therapeutic options. Retinoids are derivatives of vitamin A involved in the control of many biological functions, including cell growth and differentiation and the induction of apoptosis. On the basis of pre-clinical evidence and some clinical data, we conducted a phase II study of 13-cis-retinoic acid (13-cis-RA) in combination with gemcitabine in patients with unresectable pancreatic carcinoma. Materials and methods: Patients with histologically confirmed unresectable pancreatic carcinoma were treated with gemcitabine 1000 mg/m(2) on days 8, 15, 22 plus 13-cis-RA 1 mg/kg on days 1-14 for six cycles. The end points included the objective response rate and median survival. Results: Thirty patients were recruited, 15 men and 15 women; 20 patients were evaluable. The median age was 65 years (range 44-79 years) and the median Karnofsky performance status was 80% (range 60-100%). The median follow-up was 21 months. One patient achieved a partial remission, seven patients had stable disease and 12 patients developed progressive disease. Toxicity was mainly haematological, with eight cases of grade 3 and four cases of grade 4 neutropenia, thrombocytopenia and anaemia. The median survival was 7.8 months (range 2.6-21.6 months). Conclusions: The combination of gemcitabine and 13-cis-RA was well tolerated, but we did not see improvement in the response rate. Further studies with other retinoids may be beneficial to patients with unresectable pancreatic cancer.