Cancer Chemother Pharmacol (2014) 74:1291–1296 DOI 10.1007/s00280-014-2608-4
ORIGINAL ARTICLE
Treatment outcomes of gemcitabine alone versus gemcitabine plus platinum for advanced biliary tract cancer: a Korean Cancer Study Group retrospective analysis In Gyu Hwang · Hong Suk Song · Myung Ah Lee · Eun Mi Nam · Joohan Lim · Kyung Hee Lee · Kyu Taek Lee · Dae Young Zang · Joung-Soon Jang
Received: 8 July 2014 / Accepted: 7 October 2014 / Published online: 18 October 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose ABC-02 trial of gemcitabine plus cisplatin combination showed prolongation of overall survival in biliary tract cancer (BTC) patients. In this multicenter retrospective study, we evaluated the treatment outcome of gemcitabine combined with platinum (GP) compared to that of gemcitabine (G) alone in Korean BTC patients. Methods One hundred and fifty-one patients with histologically confirmed biliary tract adenocarcinoma were enrolled at nine institutions between July 2003 and May 2011, including 100 treated with GP and 51 treated with G. Results With a median follow-up of 7.7 months (range 0.4–38.3 months), the median overall survival (OS) was 12.4 months [95 % confidence interval (CI) 9.4– 15.6 months] of the G group, which was not significantly
different for the median OS of 11.0 months (95 % CI 9.7– 12.3 months) of the GP group (p = 0.599). The median progression-free survival (PFS) was 3.9 months (95 % CI 0.8–7.0 months) in the G group and 3.3 months (95 % CI 2.6–4.0 months) in the GP group (p = 0.504). Overall response rates (ORR) were 18.8 % in G group and 23.9 % in GP group (p = 0.485). Conclusions There was no significant difference in ORR, PFS, or OS for patients between the G group and the GP group, which was different from the ABC-02 trial. Therefore, gemcitabine monotherapy and GP combination are both effective regimens for Korean BTC patients.
I. G. Hwang · J.-S. Jang Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul 156-756, Korea
K. H. Lee Department of Internal Medicine, Yeungnam University College of Medicine, Daegu 705-717, Korea
H. S. Song Department of Internal Medicine, Keimyung University School of Medicine, Daegu 705-701, Korea
K. T. Lee Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan 330-721, Korea
M. A. Lee Division of Medical Oncology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University, Seoul 137-701, Korea
D. Y. Zang Department of Internal Medicine, Hallym University College of Medicine, Anyang 431-796, Korea
E. M. Nam Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul 158-710, Korea
Keywords Biliary tract cancer · Efficacy · Gemcitabine · Platinum · Retrospective analysis
J.-S. Jang (*) Division of Hematology/Oncology, Chung-Ang University Hospital, 224 Heukseok-dong, Dongjak-gu, Seoul 156-755, Korea e-mail: [email protected]
J. Lim Department of Internal Medicine, Inha University College of Medicine, Incheon 400-711, Korea
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Introduction Biliary tract cancers (BTCs) are highly lethal due to their advanced stage at diagnosis, critical anatomic location, and high recurrence rate after surgical treatment. Most BTCs are inoperable or metastatic, making only few patients as candidates for curative treatment. Chemotherapy remains the only one option for treatment in most patients beyond curation. However, poor response to chemotherapy makes disease prognosis worse for patients who are already in difficult treatment circumstances [2]. Lack of data on effective treatment in this advanced disease setting has led to the adoption of chemotherapy options used in pancreatic cancer. Gemcitabine-based regimens have been the standard chemotherapy option substantially in the palliative treatment of BTCs. In reality, several phase II studies have reported promising data with the use of gemcitabine-based regimen in patients with advanced BTCs, supporting the usefulness of the regimens [11]. Of various gemcitabine-based regimens, gemcitabine combined with platinum has been the most frequently employed regimen [7]. However, these studies are limited numbered phase II trials making its treatment potential still ambiguous. Furthermore, reports on the tolerability of gemcitabine–platinum dual regimens described more side effects over gemcitabine alone regimen because of platinum toxicity [6, 10]. In this study, the authors investigated the treatment outcomes of the gemcitabine and platinum combination regimens compared to gemcitabine alone in palliative treatment of BTCs using multicenter retroprospective analysis.
Materials and methods Study design A multicenter retrospective cross-sectional study was performed to evaluate the efficacy and compliance of gemcitabine combined with platinum regimens compared to the gemcitabine alone regimen in chemotherapy-naive patients with locally advanced or metastatic BTC. Patients The author retrospectively reviewed 151 patients with histologically confirmed BTCs from nine institutions in Korea between July 2000 and May 2011. Patients who were treated with the combination regimen of gemcitabine and platinum (cisplatin/C or oxaliplatin/O) or gemcitabine monotherapy were recruited for this study. The inclusion criterion was that no prior chemotherapy was given to patients. However, patients with previous adjuvant chemotherapy and/or radiation therapy administered more than
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Cancer Chemother Pharmacol (2014) 74:1291–1296
6 months before the date of enrollment were included in the study. This trial was approved by an Institutional review board at each institute. Written informed consents were obtained from all participating patients. Treatments and evaluation All patients had at least one or more courses of chemotherapy. They received the monotherapy or the combination therapy as shown in the following: For combination therapy, regimen of gemcitabine/cisplatin (GC) consisted of G at 1,000 mg/m2 i.v. on day 1, 8 and C at 70 mg/m2 i.v. on day 1 every 3 weeks. Regimen of gemcitabine/oxaliplatin (GEMOX) consisted of G at 1,000 mg/m2 i.v. on day 1, 8 and O at 100 mg/m2 i.v. on day 1 every 3 weeks, or G at 1,000 mg/m2 i.v. on day 1 and O at 85 mg/m2 i.v. on day 2 every 2 weeks. The regimen of gemcitabine alone consisted of G at 1,000 mg/m2 i.v. on day 1, 8, 15 every 4 weeks. Response to treatment was evaluated with enhanced computed tomography (CT) after every two cycles (or three cycles in the every 2 weeks regimen) of chemotherapy according to response evaluation criteria in solid tumors (RECIST) criteria. Statistical analysis Overall survival (OS) was calculated from the first day of palliative chemotherapy until the date of death or the most recent documented follow-up. Patients who were alive at the last follow-up were censored at that time. Progressionfree survival (PFS) was calculated from the first day of palliative chemotherapy to the day when disease progression was recognized or the day of the last follow-up visit. Patients who were taken off study or who died before progression were censored at the time as they were taken off. OS and PFS were estimated using the Kaplan–Meier method. Significant differences between groups were assessed by the log-rank test. All reported p values are two sided. Significant difference was considered when p value was less than 0.05. Multivariate analysis of the independent predictive or prognostic factors for survival was performed using Cox regression model with 95 % confidence intervals (CIs). Factors with p values less than 0.05 in univariate analyses were examined with multivariate regression model. Analyses were performed using SPSS version 12.0.
Results Patient characteristics One hundred (100) patients were treated with the combination therapy (gemcitabine combined with platinum). A total
Cancer Chemother Pharmacol (2014) 74:1291–1296 Table 1 Patients characteristics according to treatment group
GP gemcitabine + platinum, G gemcitabine a ECOG scores for performance status †
p Values from the χ2 or Fisher’s exact tests
Characteristic
Sex Male Female Age (years) Median (range)
ORIGINAL ARTICLE
Treatment outcomes of gemcitabine alone versus gemcitabine plus platinum for advanced biliary tract cancer: a Korean Cancer Study Group retrospective analysis In Gyu Hwang · Hong Suk Song · Myung Ah Lee · Eun Mi Nam · Joohan Lim · Kyung Hee Lee · Kyu Taek Lee · Dae Young Zang · Joung-Soon Jang
Received: 8 July 2014 / Accepted: 7 October 2014 / Published online: 18 October 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose ABC-02 trial of gemcitabine plus cisplatin combination showed prolongation of overall survival in biliary tract cancer (BTC) patients. In this multicenter retrospective study, we evaluated the treatment outcome of gemcitabine combined with platinum (GP) compared to that of gemcitabine (G) alone in Korean BTC patients. Methods One hundred and fifty-one patients with histologically confirmed biliary tract adenocarcinoma were enrolled at nine institutions between July 2003 and May 2011, including 100 treated with GP and 51 treated with G. Results With a median follow-up of 7.7 months (range 0.4–38.3 months), the median overall survival (OS) was 12.4 months [95 % confidence interval (CI) 9.4– 15.6 months] of the G group, which was not significantly
different for the median OS of 11.0 months (95 % CI 9.7– 12.3 months) of the GP group (p = 0.599). The median progression-free survival (PFS) was 3.9 months (95 % CI 0.8–7.0 months) in the G group and 3.3 months (95 % CI 2.6–4.0 months) in the GP group (p = 0.504). Overall response rates (ORR) were 18.8 % in G group and 23.9 % in GP group (p = 0.485). Conclusions There was no significant difference in ORR, PFS, or OS for patients between the G group and the GP group, which was different from the ABC-02 trial. Therefore, gemcitabine monotherapy and GP combination are both effective regimens for Korean BTC patients.
I. G. Hwang · J.-S. Jang Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul 156-756, Korea
K. H. Lee Department of Internal Medicine, Yeungnam University College of Medicine, Daegu 705-717, Korea
H. S. Song Department of Internal Medicine, Keimyung University School of Medicine, Daegu 705-701, Korea
K. T. Lee Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan 330-721, Korea
M. A. Lee Division of Medical Oncology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University, Seoul 137-701, Korea
D. Y. Zang Department of Internal Medicine, Hallym University College of Medicine, Anyang 431-796, Korea
E. M. Nam Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul 158-710, Korea
Keywords Biliary tract cancer · Efficacy · Gemcitabine · Platinum · Retrospective analysis
J.-S. Jang (*) Division of Hematology/Oncology, Chung-Ang University Hospital, 224 Heukseok-dong, Dongjak-gu, Seoul 156-755, Korea e-mail: [email protected]
J. Lim Department of Internal Medicine, Inha University College of Medicine, Incheon 400-711, Korea
13
1292
Introduction Biliary tract cancers (BTCs) are highly lethal due to their advanced stage at diagnosis, critical anatomic location, and high recurrence rate after surgical treatment. Most BTCs are inoperable or metastatic, making only few patients as candidates for curative treatment. Chemotherapy remains the only one option for treatment in most patients beyond curation. However, poor response to chemotherapy makes disease prognosis worse for patients who are already in difficult treatment circumstances [2]. Lack of data on effective treatment in this advanced disease setting has led to the adoption of chemotherapy options used in pancreatic cancer. Gemcitabine-based regimens have been the standard chemotherapy option substantially in the palliative treatment of BTCs. In reality, several phase II studies have reported promising data with the use of gemcitabine-based regimen in patients with advanced BTCs, supporting the usefulness of the regimens [11]. Of various gemcitabine-based regimens, gemcitabine combined with platinum has been the most frequently employed regimen [7]. However, these studies are limited numbered phase II trials making its treatment potential still ambiguous. Furthermore, reports on the tolerability of gemcitabine–platinum dual regimens described more side effects over gemcitabine alone regimen because of platinum toxicity [6, 10]. In this study, the authors investigated the treatment outcomes of the gemcitabine and platinum combination regimens compared to gemcitabine alone in palliative treatment of BTCs using multicenter retroprospective analysis.
Materials and methods Study design A multicenter retrospective cross-sectional study was performed to evaluate the efficacy and compliance of gemcitabine combined with platinum regimens compared to the gemcitabine alone regimen in chemotherapy-naive patients with locally advanced or metastatic BTC. Patients The author retrospectively reviewed 151 patients with histologically confirmed BTCs from nine institutions in Korea between July 2000 and May 2011. Patients who were treated with the combination regimen of gemcitabine and platinum (cisplatin/C or oxaliplatin/O) or gemcitabine monotherapy were recruited for this study. The inclusion criterion was that no prior chemotherapy was given to patients. However, patients with previous adjuvant chemotherapy and/or radiation therapy administered more than
13
Cancer Chemother Pharmacol (2014) 74:1291–1296
6 months before the date of enrollment were included in the study. This trial was approved by an Institutional review board at each institute. Written informed consents were obtained from all participating patients. Treatments and evaluation All patients had at least one or more courses of chemotherapy. They received the monotherapy or the combination therapy as shown in the following: For combination therapy, regimen of gemcitabine/cisplatin (GC) consisted of G at 1,000 mg/m2 i.v. on day 1, 8 and C at 70 mg/m2 i.v. on day 1 every 3 weeks. Regimen of gemcitabine/oxaliplatin (GEMOX) consisted of G at 1,000 mg/m2 i.v. on day 1, 8 and O at 100 mg/m2 i.v. on day 1 every 3 weeks, or G at 1,000 mg/m2 i.v. on day 1 and O at 85 mg/m2 i.v. on day 2 every 2 weeks. The regimen of gemcitabine alone consisted of G at 1,000 mg/m2 i.v. on day 1, 8, 15 every 4 weeks. Response to treatment was evaluated with enhanced computed tomography (CT) after every two cycles (or three cycles in the every 2 weeks regimen) of chemotherapy according to response evaluation criteria in solid tumors (RECIST) criteria. Statistical analysis Overall survival (OS) was calculated from the first day of palliative chemotherapy until the date of death or the most recent documented follow-up. Patients who were alive at the last follow-up were censored at that time. Progressionfree survival (PFS) was calculated from the first day of palliative chemotherapy to the day when disease progression was recognized or the day of the last follow-up visit. Patients who were taken off study or who died before progression were censored at the time as they were taken off. OS and PFS were estimated using the Kaplan–Meier method. Significant differences between groups were assessed by the log-rank test. All reported p values are two sided. Significant difference was considered when p value was less than 0.05. Multivariate analysis of the independent predictive or prognostic factors for survival was performed using Cox regression model with 95 % confidence intervals (CIs). Factors with p values less than 0.05 in univariate analyses were examined with multivariate regression model. Analyses were performed using SPSS version 12.0.
Results Patient characteristics One hundred (100) patients were treated with the combination therapy (gemcitabine combined with platinum). A total
Cancer Chemother Pharmacol (2014) 74:1291–1296 Table 1 Patients characteristics according to treatment group
GP gemcitabine + platinum, G gemcitabine a ECOG scores for performance status †
p Values from the χ2 or Fisher’s exact tests
Characteristic
Sex Male Female Age (years) Median (range)
