Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
* Correspondence to: Dr S. Thongprasert, Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chiang Mai University, 110 Intawaroros Road, Chiang Mai 50200, Thailand. Tel: +66-53-945477; Fax: +66-53-215600; Email: sthongpr{at}mail.med.cmu.ac.th
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Abstract |
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Methods: From December 2000 to July 2002, 43 patients received gemcitabine 1250 mg/m2 in a 30-min i.v. infusion on d1, 8 and cisplatin 75 mg/m2 in a 2-h i.v. infusion on d1 (with appropriate hydration), every 3 weeks.
Eligibility: Normal hematologic parameters and creatinine levels; serum bilirubin <5 mg/dl.
Results: Forty-three patients enrolled; 40 were assessable (three patients were not assessable due to incomplete treatment; they chose to discontinue chemotherapy after the first cycle). There were 23 males and 17 females, median age 50 years (range 3169), median Karnofsky PS 80%. Tumor types: cholangiocarcinoma (39), gall bladder cancer (1). Median number of chemotherapy courses was four (range 18). Overall response rate was 27.5% (PR in 11 pts), with 32.5% SD and/or minor response. Median survival time was 36 weeks. Grade 3 hematologic toxicity: anemia (4.33%), leukopenia (1.73%). Non-hematologic toxicity (i.e. rash, nausea, vomiting, neuropathy and myalgia) ranged from mild to moderate.
Conclusions: Gemcitabine plus cisplatin is active in biliary tract carcinoma. These data warrant further investigation of single-agent gemcitabine versus gemcitabine plus cisplatin or its derivative, i.e. oxaliplatin.
Key words: biliary tract carcinoma, cisplatin, gemcitabine
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Introduction |
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In Thailand, we have a high incidence of cholangiocarcinoma and we primarily explored the response to gemcitabine plus cisplatin in cholangiocarcinoma/bile duct tumors, and gall bladder adenocarcinomas. Our secondary objective was to determine the time to disease progression, overall survival and toxicity.
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Patients and methods |
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Schema of study
Patients who met the eligibility criteria were given gemcitabine at 1250 mg/m2/day by 30-min intravenous infusion on days 1 and 8, and cisplatin at 75 mg/m2/day by 2-h intravenous infusion on day 1, repeated every 21 days. Physical examination and symptom assessment were made every 3 weeks and computed tomography scans were carried out at 12 weeks. The patients were treated until the appearance of disease progression or unacceptable toxicity. If the disease responded, treatment might continue for two more cycles. If the disease was stable or progressed at 12 weeks, treatment was discontinued and the patients were kept on follow up.
Dose modification for gemcitabine
The dose of gemcitabine was reduced to 1000 mg/m2 in subsequent cycles in the case of an ANC nadir of <500/mm3 for >7 days, a platelet nadir of <50 000/mm3 for >7 days, any grade of thrombocytopenia associated with bleeding, or febrile neutropenia. Once a dose reduction for subsequent cycles was required, re-escalation of dose was not allowed. Also no second dose reduction was allowed. If the above toxic effects recurred at a reduced dose level, study treatment had to be discontinued and the patient was taken off the study.
The day 8 dose of gemcitabine was reduced to 1000 mg/m2 in the case of an ANC of 10001500/mm3, and platelets of
50 000100 000/mm3. In the case of ANC or platelet counts lower than the above, the day 8 dose of gemcitabine was omitted. Day 8 dose reductions or omissions of gemcitabine did not affect dosing in the subsequent cycles and could be carried out in as many treatment cycles as required. The subsequent chemotherapy cycle was given on time if the ANC was >1500/mm3 and platelets >100 000/mm3. If lower, chemotherapy was postponed for a minimum of 1 week. If counts did not reach the above values after 2 weeks, chemotherapy was discontinued.
Evaluation criteria
All patients were assessable for toxicity from the time of the first chemotherapy dose. All patients who underwent two or more treatment cycles were assessable for a response. Standard tumor measurements were used, in keeping with the following definitions: CR was defined as a complete disappearance of the tumor for at least 4 weeks after time documentation; PR was defined as more than a 50% decrease in the sum of the products of the two largest perpendicular diameters of all measurable lesions, as determined 4 weeks apart, consecutively; stable disease (SD) was defined as not only no CR or PR, but also no objective progression; progressive disease (PD) was defined as a 25% or greater increase in the size of any measurable lesion or the appearance of new lesions or ascites.
Time to progression was calculated from the first treatment day to the identification date of progressive disease or death. Duration of response was measured from the date of response notation to the first record of disease progression or death, and survival was measured from the first day of treatment to death.
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Results |
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Discussion |
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Acknowledgements |
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Received for publication March 15, 2004. Revision received August 4, 2004. Accepted for publication September 15, 2004.
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References |
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