Annals of Oncology 17 (Supplement 5): v133–v136, 2006 doi:10.1093/annonc/mdj968 symposium article A phase II study of Gemcitabine and immunotherapy in renal cancer: preliminary results and review of the literature F. Zustovich 1 *, G. Cartei 1 , M. Dal Bianco 2 , L. De Zorzi 2 , R. Ceravolo 1 , S. Zovato 1 , F. Salmaso 1 , S. Binato 1 , G. Artioli 1 , S. Cingarlini 1 & D. Pastorelli 1 1 O.U.C. Medical Oncology, Busonera Hospital 1 st floor, National Oncology Institute of Veneto (IOV – IRCCS ) Padua, Italy; 2 Division of Urology, ULSS 16, S. Antonio Hospital, Padua, Italy Key words: renal cancer, Gemcitabine, immunotherapy Renal cancer remains a challenge for oncologists since no treatment other than surgery has demonstrated a clear survival advantage. Immunotherapy probably prolongs survival in a subset of good prognosis patients. Chemotherapy alone or in combination with immunotherapy has not improved the patients’ outcome. We performed a phase II trial of Gemcitabine (G) given at fixed infusion rate of 10 mg/m 2 /min chemotherapy with or without concomitant immunotherapy. The overall response rate of 17% and the median survival of 11.6+ months represent an encouraging result, especially considering the poor prognostic features of our patient population. Stability of disease occurred in 12 (50%) patients. Toxicity has not been mild, even though not life threatening, with fatigue in 3 pts and anemia in 3 pts. background Renal cell carcinoma represents about 3% of all malignant tumours. In the US there have been 31 900 new cases in 2003 with 11 900 related deaths (27% rate) [1]. Treatment strategy is based on surgery and overall survival depends on pathological stage and on some prognostic factors as Fuhrman’s grade and performance status [2]. No adjuvant treatment has demonstrated a survival advantage. Median survival for metastatic disease is 10 months with a small quote of long-term survivors (8.5% at 5 years) [3]. Nephrectomy in addition to immunotherapy (a-interferon) seems to increase the overall survival [4, 5]. No other treatment achieves the evidence of a survival gain among randomized studies. A survival benefit by means of an interleukin-2 based regimen is possible for a subset of good-prognosis patients [6]. Chemotherapy has not demonstrated any survival advantage as well as the combination with immunotherapy. Fluorodeoxyuridine, Fluorouracil and Vinblastine are believed to be the most effective single-agent chemotherapy for the advanced renal cell carcinoma with response rates within 13% [7]. Among the new agents, Gemcitabine seems to give the most effective response rate, even up to 31% [8]. Gemcitabine does not affect lymphocyte immune-reactive activity in patients with solid tumors and it seems to be synergistic with immunotherapy in animal models [9, 10]. Protracted Gemcitabine infusion (time >30 min) causes an increased intracellular rate of active metabolites enhancing Gemcitabine therapeutic and toxic effects [11]. Our experience in lung cancer patients showed that, in well fit subjects, Gemcitabine doses up to 1200 mg/m 2 in 120’ infusion day 1, 8, 15 every 4 weeks are safe; while lower doses are recommended in poor performance status patients [12]. Considering the promising response rate obtainable with Gemcitabine and the opportunity of combining immunotherapy to the drug, we started a protracted infusion (10 mg/m 2 /m) Gemcitabine-based phase II study. patients and methods Patients evaluated in our Institution were prospectively enrolled into the study. No particularly restrictive selection criteria were adopted. Patients with advanced progressive renal cancer eligible for chemotherapeutic treatment were recruited. Gemcitabine was administered at an infusion rate of 10 mg/m 2 /min on day 1, 8, 15 of a 28 days cycle. Time of infusion was in function of age and ECOG PS. Immunotherapy was added if not or inadequate prior immunotherapy was previously given. Combination chemotherapy with Doxorubicine was used in a case of sarcomatoid variant of renal cancer [13]. Topotecan in combination with Gemcitabine was administered to a single patient whose induced topoisomerases suppression by Topotecan was evaluated after the Gemcitabine infusion [14]. results From June 2001 and March 2005 we enrolled 25 patients, whose characteristics are reported in Table 1. All patients underwent symposium article *Correspondence to: Dr F. Zustovich, O.U.C. Medical Oncology, 1 st floor, Busonera Hospital, via Gattamelata 64, 35128 Padova, Italy. Tel: +39-3479775504; Fax: +39-049.8215904; E-mail: fzustovich@ulss16.padova.it ª 2006 European Society for Medical Oncology by guest on September 29, 2013 http://annonc.oxfordjournals.org/ Downloaded from by guest on September 29, 2013 http://annonc.oxfordjournals.org/ Downloaded from by guest on September 29, 2013 http://annonc.oxfordjournals.org/ Downloaded from by guest on September 29, 2013 http://annonc.oxfordjournals.org/ Downloaded from