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Byline: Nikolas Tsavaris (1,2), Christos Kosmas (1,2), Panagiotis Gouveris (1,2), Kostadinos Gennatas (1,3), Aris Polyzos (4), Despina Mouratidou (1,5), Heracles Tsipras (6), Helias Margaris (6), George Papastratis (6), Evanthia Tzima (1,2), Nikitas Papadoniou (7), Gavrilos Karatzas (8), Efstathios Papalambros (7) Keywords: cholangiocarcinoma; gemcitabine; biliary tract cancer; gallbladder cancer Abstract: Objectives: To evaluate the efficacy and safety of weekly administration of gemcitabine treatment in chemotherapy-naive patients with advanced biliary tract and gallbladder cancer. Patients and methods: Gemcitabine at a dose of 800mg/m.sup.2 was administered weekly as a 30-min infusion to patients with previously operated, histologically confirmed, metastatic, or unresectable locally advanced cholangiocarcinoma. Treatment was continued until unacceptable toxicity or disease progression. Results: A total of 30 patients (median age 66 years; range 54--72 years) were included in the study. A median of 14 (range, 4--33) weekly doses was administered. Out of 30 patients evaluable for response, nine partial responses were observed (30.0%), while a further 11 patients demonstrated stable disease (36.7%). The median time to disease progression was 7 months (range, 5--34). Overall response rate was superior in patients with cancer of the gallbladder (ORR=35.7%) compared with those patients with biliary duct cancer (ORR=27.3%). This correlated to a significantly longer time to progression of 6.4 months (95% confidence interval (CI), 5.6--7.1 months) versus 3.6 months (95% CI, 2.9--4.3 months; p=0.03) and a significantly better overall survival of 17.1 months (95% CI, 15.8--18.5 months) versus 11.4 months (95% CI, 10.2--12.6 months, p=0.021). Toxicities were generally mild with only one case of grade 3 neutropenia. There were no cases of febrile neutropenia and no treatment-related deaths. Conclusions: Weekly administration of gemcitabine provides a safe, well-tolerated, and effective treatment for chemotherapy naive patients with advanced cholangiocarcinoma, particularly with a gallbladder origin. Author Affiliation: (1) 'HELGO' Hellenic Group of Oncology, Athens, Greece (2) Oncology Unit, Department of Pathophysiology, 'Laiko' General Hospital, University of Athens, Athens, Greece, 11527 (3) Oncology Unit, 2nd Department Surgery, 'Areteion' General Hospital, University of Athens, Greece (4) Oncology Unit, 1st Department of Internal Medicine -- Propeduetic, 'Laiko' Hospital, University of Athens, Athens, Greece (5) 2nd Department of Medical Oncology, 'Theagenion' Cancer Hospital, Thessaloniki (6) 3rd Department of Surgery, 'G. Genimatas' General Hospital, Athens, Greece (7) 1st Department of Surgery, 'Laiko' General Hospital, University of Athens, Athens, Greece (8) 3rd Department of Surgery, 'Sotiria' Hospital, University of Athens, Athens, Greece Article History: Registration Date: 21/10/2004

Byline: Emilio Esteban (1), Joaquin Fra (1), Marian Sala (1), Juan Carrasco (1), Norberto Corral (1), Jose Maria Vieitez (1), Enrique Estrada (1), Isabel Palacio (1), Jose Mari Buesa (1), Angel J. Lacave (1) Abstract: Purpose. We determine the maximum tolerated dose (MTD) and efficacy ofgemcitabine plus vinorelbine combined withcisplatin in patients with non-small celllung cancer (NSCLC). Patients and methods. Chemo naive patientswith stage IIIA to IV non-small cell lungcancer received outpatient administrationof gemcitabine 1000 mg/m.sup.2 andvinorelbine 25 mg/m.sup.2 intravenously ondays 1 and 8 every 21 days. Doses ofgemcitabine and vinorelbine were escalatedby 250 mg/m.sup.2 and 5 mg/m.sup.2,respectively, at each dose level. Cisplatin was administered at a fixed doseof 50 mg/m.sup.2 on days 2 and 9. Afterthe MTD was reached, the study wascontinued as a phase II trial. Results. From January 1998 to March 1999, sixty-five patients were enrolled. Thefirst 38 patients participated in the phaseI evaluation. After 130 cycles, thedose-limiting toxicities were neutropenia,stomatitis, asthenia, and hepatotoxicityoccurring at the third and fourth doselevels (doses of gemcitabine/vinorelbine of1500/25 and 1000/30 mg/m.sup.2).For the subsequent phase II evaluation, 27additional patients, out of a total of 53,receiving the MTD of gemcitabine andvinorelbine (1000--1250/25 mg/m.sup.2)followed (24 hours later) by cisplatin50 mg/m.sup.2. Thirty one (58%) of 53 assessable patients responded. Objectiveresponse for patients with stages III andIV disease, respectively, were 65% and47%. The median time to progression andthe overall survival time were 9 months(95% CI: 5--12) and 11 months (95 % CI:9--13), respectively. World HealthOrganization toxicity aY= grade 3neutropenia was registered in 28 (54%) of52 assessable patients (2% with febrileneutropenia), and aY= grade 3thrombocytopenia in 15 (29%) patients (4%with bleeding). Nausea/vomiting(aY= grade 2) and asthenia (moderate tosevere) occurred in 24 (46%) and 14 (27%)patients, respectively. Conclusion. Gemcitabine1000--1250 mg/m plus vinorelbine25 mg/m.sup.2 on days 1 and 8, followed bycisplatin 50 mg/m.sup.2 24 hours later, issafe for outpatient administration andactive in patients with NSCLC. Author Affiliation: (1) Servicio de Oncologia Medica, Hospital Central de Asturias, Oviedo, Spain Article History: Registration Date: 10/10/2004

Byline: James K. Weick (1), John J. Crowley (2), Mohamed A. Hussein (3), Dennis F. Moore (4), Bart Barlogie (5) Keywords: gemcitabine; multiple myeloma; phase II Abstract: Gemcitabine is a cytosine arabinoside(Ara-C) analog with activity in many humantumor systems. We evaluated the drug'sactivity in resistant or relapsing multiplemyeloma. Gemcitabine 1000 mg/m.sup.2 wasadministered as a 30 minute infusion ondays 1, 8, and 15 of a 28-day cycle. Nodose escalations were permitted and dosereductions were scheduled for hematologictoxicity. Twenty-nine eligible patientswere entered into Southwest Oncology Group(SWOG)-9803. One patient received notreatment and 5 patients had inadequateresponse assessments. The major toxicitywas hematologic with grade 3/4 neutropeniain 9 and grade 3/4 thrombocytopenia in 15patients. No responses were seen. Stabledisease was confirmed in sixteen patients(57%). Median survival was eight months. Gemcitabine as utilized in this trial hasshown little activity and is not to bestrongly considered for future multiplemyeloma trials. Author Affiliation: (1) Hematology Oncology Associates, Lake Worth, FL, USA (2) Southwest Oncology Group Statistical Center, Seattle, WA, USA (3) Cleveland Clinic Foundation, Cleveland, OH, USA (4) Wichita Community Clinical Oncology Program, Wichita, KS, USA (5) University of Arkansas for Medical Science, Little Rock, AR, USA Article History: Registration Date: 10/10/2004

Byline: Christian Manegold (1), Petr Zatloukal (2), Kurt Krejcy (3), Johannes Blatter (4) Keywords: gemcitabine; NSCLC; review; efficacy; toxicity; randomization Abstract: The role of chemotherapy in the treatment of non-smallcell lung cancer (NSCLC) has increased greatly in the past fewyears. While cytotoxic drugs are currently used both as singleagents and in combination for palliation in locally advanced andmetastatic disease, they have also been incorporated intomulti-modality treatment strategies of Stage I to Stage IIINSCLC. One of the main reasons for the increased acceptance ofchemotherapy is the development of new substances. Among the most promising of these new drugs is theantimetabolite gemcitabine. Several single-arm gemcitabine PhaseII studies involving more than 400 patients show validatedresponse rates in more than 20% of the patients. Thesepositive results have also been confirmed in randomized Phase IIstudies. Gemcitabine's unique mechanism of action, its lack ofoverlapping toxicity with other agents, and its favorabletoxicity profile also define it as an ideal candidate forcombination therapy. The activity seen with single-agent gemcitabine therapy canbe compared with that of cisplatin-etoposide combination therapy.Gemcitabine-cisplatin combination response rates range from31% to 54%, with a median survival time between 8.4and 15.4 months and a 1-year survival rate between 30% and59%. In addition to the clinical research ofgemcitabine-cisplatin combinations, gemcitabine has also beentested in various double and triple combinations withcarboplatin, paclitaxel, docetaxel, vinorelbine, and ifosfamide.Investigations combining gemcitabine with radiation therapy areon-going. The following review will summarize results fromrepresentative Phase I/II and III studies using gemcitabine forNSCLC patients. Author Affiliation: (1) Thoraxklinik der LVA, University Teaching Hospital, Heidelberg, Germany (2) Faculty Hospital Na Bulovce, Charles University and Postgraduate Medical School, 3rd Faculty of Medicine, Prague, Czech Republic (3) Eli Lilly GmbH, Area Medical Center, Vienna, Austria (4) Lilly Deutschland GmbH, Bad Homburg, Germany Article History: Registration Date: 05/10/2004