Clinical Study Received: April 24, 2013 Accepted after revision: September 3, 2013 Published online: October 29, 2013
Oncology 2013;85:262–268 DOI: 10.1159/000355690
Sequential Chemotherapies for Advanced Gastric Cancer: A Retrospective Analysis of 111 Patients Christoph Elsing a Christina Herrmann c Carla Verena Hannig b Wolfgang Stremmel d Dirk Jäger c Thomas Herrmann e
a
Department of Internal Medicine, Gastroenterology and Metabolic Diseases and b Medical Practice for Oncology and Haematology, St. Elisabeth Hospital, Dorsten, Departments of c Medical Oncology, National Center for Tumor Diseases and d Gastroenterology, University Hospital Heidelberg, Heidelberg, and e Klinikum Idar-Oberstein GmbH, Idar-Oberstein, Germany
Key Words Gastric cancer · Second-line chemotherapy
Abstract Background: The role of second-line chemotherapy in advanced gastric cancer is not yet fully established. Patients and Methods: We analysed 111 patients with advanced gastric cancer treated at the University Hospital Heidelberg (51) and the private oncology practice Bottrop/Dorsten (60) between 2001 and 2011, comparing the outcome of patients with first-line chemotherapy and those who received second-line chemotherapy. Results: Thirty-six patients were treated with one chemotherapy regimen, 75 patients received at least two different chemotherapies. Patients who received one chemotherapy regimen were older (median age 69 years) and had a shorter overall survival (6 months) than patients receiving sequential chemotherapies [median age 61 years, p = 0.009, overall survival 14 months (2–42), p = 0.001]. Under second-line chemotherapy, partial response was observed in 25 patients (33%) and stable disease for ≥3 months in 26 patients (35%). Patients treated before 2005 had a slightly better overall survival than patients treated in or after 2005. Survival was not influenced by the treatment centre (primary or tertiary), but was influenced by former
© 2013 S. Karger AG, Basel 0030–2414/13/0855–0262$38.00/0 E-Mail [email protected] www.karger.com/ocl
surgery. Conclusion: The prognosis of advanced gastric cancer is still poor. Selected patients may benefit from individualized salvage chemotherapy after failure of first-line chemotherapy. © 2013 S. Karger AG, Basel
Introduction
Patients with advanced gastric cancer benefit from palliative chemotherapy. Several randomized trials have demonstrated that systemic chemotherapy prolongs survival and improves quality of life compared to best supportive care alone [1–4]. However, the role of second-line chemotherapy after treatment failure or intolerability of first-line chemotherapy was controversial until recently. Several phase II trials have investigated the role of second-line chemotherapy and indicated that a subset of patients may benefit from salvage chemotherapy [5–8]. Recently, two randomized phase III studies showing a benefit of second-line chemotherapy in advanced gastric cancer have been published [9, 10].
C.E. and C.H. contributed equally to this work.
Christoph Elsing, MD Department of Internal Medicine, Gastroenterology and Metabolic Diseases St. Elisabeth Hospital, Pfarrer Wilhelm Schmitz Strasse 1 DE–46282 Dorsten (Germany) E-Mail dr.c.elsing @ kkrn.de
Downloaded by: University of Edinburgh 149.126.76.1 - 7/23/2015 10:25:00 PM
Patients and Methods Patients We analysed the data of 51 patients treated at the University Hospital Heidelberg because of advanced gastric cancer, and the data of 60 patients treated in a community-based specialized practice. Patients were required to have histologically proven inoperable or metastatic carcinoma of the stomach. Patients who started treatment between January 2001 and July 2011 were included in this study. All patients received the entire treatment at our departments. Older patients or patients with poor performance status or comorbidity were not excluded from this study. Fifty patients (44%) were female and 61 (56%) were male. The median age was 63 years (range 29–82). At the time of analysis, all patients were deceased. The study concept was reviewed by the ethical committee of the University of Heidelberg. Treatment In this retrospective analysis, different chemotherapy regimens were used according to the decision of the attending physician. First-line therapy was cisplatin/5-fluorouracil (5-FU)/folinic acid (FA; PLF) in 61 cases (55%), etoposide/5-FU/FA (ELF) in 11 cases (10%), oxaliplatin/5-FU/FA (FLO) in 11 cases (10%), irinotecan/ infusional 5-FU/FA in 5 cases (5%), cisplatin/gemcitabine in 1 case (1%), cisplatin/docetaxel/5-FU in 2 cases (2%), infusional 5-FU/ FA in 6 cases (5%), epirubicin/oxaliplatin/capecitabine in 5 cases (5%), cisplatin/5-FU/FA/trastuzumab in 1 case (1%), oxaliplatin/5FU/FA/trastuzumab in 1 case (1%), oxaliplatin/5-FU/FA/docetaxel in 1 case (1%), irinotecan in 1 case (1%), and capecitabine in 5 case (5%). Second-line chemotherapy was irinotecan/5-FU/FA in 16 patients (21%), irinotecan mono in 14 cases (19%), oxaliplatin/5-FU/ FA in 10 patients (13%), ELF in 8 patients (11%), PLF in 4 case (5%), gemcitabine in 1 case (1%), epirubicin/paclitaxel in 1 case (1%), docetaxel in 5 cases (6%), capecitabine in 8 cases (11%), and other combinations in 8 patients (11%). Nineteen patients (25%) received more than two treatment regimens. Docetaxel was administered in 8 patients (42%), irinotecan-containing regimens were given to 5 patients (26%), 3 received capecitabine (16%) and the others received different combination regimens. We also investigated the effect of previous surgery (either curative or palliative) in both groups of patients on overall survival. The characteristics of the patients and the applied chemotherapy regimens are listed in table 1.
Table 1. Patient characteristics
Patients, n Female Male Median age, years (range)
111 50 (44%) 61 (56%) 63 (29–82)
One chemotherapy regimen Patients, n Female Male Median age, years (range)
36 (32%) 10 (28%) 26 (72%) 69 (47–81)
More than 1 chemotherapy regimen Patients, n Female Male Median age, years (range)
75 (68%) 40 (53%) 35 (47%) 61 (29–82)
First-line chemotherapy (n = 111) PLF ELF Oxaliplatin/5-FU/FA Irinotecan/5-FU/FA Other
61 (55%) 11 (10%) 11 (10%) 5 (4.5%) 23 (21%)
Second-line chemotherapy (n = 75) Irinotecan/5-FU/FA Irinotecan Oxaliplatin/5-FU/FA ELF PLF Other
16 (21%) 14 (19%) 10 (13%) 8 (11%) 4 (5%) 23 (31%)
were evaluated by performance status, laboratory results including tumour markers (CEA, CA 72.4) and indirect signs as pleural effusion or ascites. Statistical Analysis Overall survival was assessed from the time of diagnosis of metastatic disease or tumour relapse. Time to progression (TTP) was assessed from the start of chemotherapy. Data are shown as median and range. Values were compared by the Mann-Whitney U test. A p value
Oncology 2013;85:262–268 DOI: 10.1159/000355690
Sequential Chemotherapies for Advanced Gastric Cancer: A Retrospective Analysis of 111 Patients Christoph Elsing a Christina Herrmann c Carla Verena Hannig b Wolfgang Stremmel d Dirk Jäger c Thomas Herrmann e
a
Department of Internal Medicine, Gastroenterology and Metabolic Diseases and b Medical Practice for Oncology and Haematology, St. Elisabeth Hospital, Dorsten, Departments of c Medical Oncology, National Center for Tumor Diseases and d Gastroenterology, University Hospital Heidelberg, Heidelberg, and e Klinikum Idar-Oberstein GmbH, Idar-Oberstein, Germany
Key Words Gastric cancer · Second-line chemotherapy
Abstract Background: The role of second-line chemotherapy in advanced gastric cancer is not yet fully established. Patients and Methods: We analysed 111 patients with advanced gastric cancer treated at the University Hospital Heidelberg (51) and the private oncology practice Bottrop/Dorsten (60) between 2001 and 2011, comparing the outcome of patients with first-line chemotherapy and those who received second-line chemotherapy. Results: Thirty-six patients were treated with one chemotherapy regimen, 75 patients received at least two different chemotherapies. Patients who received one chemotherapy regimen were older (median age 69 years) and had a shorter overall survival (6 months) than patients receiving sequential chemotherapies [median age 61 years, p = 0.009, overall survival 14 months (2–42), p = 0.001]. Under second-line chemotherapy, partial response was observed in 25 patients (33%) and stable disease for ≥3 months in 26 patients (35%). Patients treated before 2005 had a slightly better overall survival than patients treated in or after 2005. Survival was not influenced by the treatment centre (primary or tertiary), but was influenced by former
© 2013 S. Karger AG, Basel 0030–2414/13/0855–0262$38.00/0 E-Mail [email protected] www.karger.com/ocl
surgery. Conclusion: The prognosis of advanced gastric cancer is still poor. Selected patients may benefit from individualized salvage chemotherapy after failure of first-line chemotherapy. © 2013 S. Karger AG, Basel
Introduction
Patients with advanced gastric cancer benefit from palliative chemotherapy. Several randomized trials have demonstrated that systemic chemotherapy prolongs survival and improves quality of life compared to best supportive care alone [1–4]. However, the role of second-line chemotherapy after treatment failure or intolerability of first-line chemotherapy was controversial until recently. Several phase II trials have investigated the role of second-line chemotherapy and indicated that a subset of patients may benefit from salvage chemotherapy [5–8]. Recently, two randomized phase III studies showing a benefit of second-line chemotherapy in advanced gastric cancer have been published [9, 10].
C.E. and C.H. contributed equally to this work.
Christoph Elsing, MD Department of Internal Medicine, Gastroenterology and Metabolic Diseases St. Elisabeth Hospital, Pfarrer Wilhelm Schmitz Strasse 1 DE–46282 Dorsten (Germany) E-Mail dr.c.elsing @ kkrn.de
Downloaded by: University of Edinburgh 149.126.76.1 - 7/23/2015 10:25:00 PM
Patients and Methods Patients We analysed the data of 51 patients treated at the University Hospital Heidelberg because of advanced gastric cancer, and the data of 60 patients treated in a community-based specialized practice. Patients were required to have histologically proven inoperable or metastatic carcinoma of the stomach. Patients who started treatment between January 2001 and July 2011 were included in this study. All patients received the entire treatment at our departments. Older patients or patients with poor performance status or comorbidity were not excluded from this study. Fifty patients (44%) were female and 61 (56%) were male. The median age was 63 years (range 29–82). At the time of analysis, all patients were deceased. The study concept was reviewed by the ethical committee of the University of Heidelberg. Treatment In this retrospective analysis, different chemotherapy regimens were used according to the decision of the attending physician. First-line therapy was cisplatin/5-fluorouracil (5-FU)/folinic acid (FA; PLF) in 61 cases (55%), etoposide/5-FU/FA (ELF) in 11 cases (10%), oxaliplatin/5-FU/FA (FLO) in 11 cases (10%), irinotecan/ infusional 5-FU/FA in 5 cases (5%), cisplatin/gemcitabine in 1 case (1%), cisplatin/docetaxel/5-FU in 2 cases (2%), infusional 5-FU/ FA in 6 cases (5%), epirubicin/oxaliplatin/capecitabine in 5 cases (5%), cisplatin/5-FU/FA/trastuzumab in 1 case (1%), oxaliplatin/5FU/FA/trastuzumab in 1 case (1%), oxaliplatin/5-FU/FA/docetaxel in 1 case (1%), irinotecan in 1 case (1%), and capecitabine in 5 case (5%). Second-line chemotherapy was irinotecan/5-FU/FA in 16 patients (21%), irinotecan mono in 14 cases (19%), oxaliplatin/5-FU/ FA in 10 patients (13%), ELF in 8 patients (11%), PLF in 4 case (5%), gemcitabine in 1 case (1%), epirubicin/paclitaxel in 1 case (1%), docetaxel in 5 cases (6%), capecitabine in 8 cases (11%), and other combinations in 8 patients (11%). Nineteen patients (25%) received more than two treatment regimens. Docetaxel was administered in 8 patients (42%), irinotecan-containing regimens were given to 5 patients (26%), 3 received capecitabine (16%) and the others received different combination regimens. We also investigated the effect of previous surgery (either curative or palliative) in both groups of patients on overall survival. The characteristics of the patients and the applied chemotherapy regimens are listed in table 1.
Table 1. Patient characteristics
Patients, n Female Male Median age, years (range)
111 50 (44%) 61 (56%) 63 (29–82)
One chemotherapy regimen Patients, n Female Male Median age, years (range)
36 (32%) 10 (28%) 26 (72%) 69 (47–81)
More than 1 chemotherapy regimen Patients, n Female Male Median age, years (range)
75 (68%) 40 (53%) 35 (47%) 61 (29–82)
First-line chemotherapy (n = 111) PLF ELF Oxaliplatin/5-FU/FA Irinotecan/5-FU/FA Other
61 (55%) 11 (10%) 11 (10%) 5 (4.5%) 23 (21%)
Second-line chemotherapy (n = 75) Irinotecan/5-FU/FA Irinotecan Oxaliplatin/5-FU/FA ELF PLF Other
16 (21%) 14 (19%) 10 (13%) 8 (11%) 4 (5%) 23 (31%)
were evaluated by performance status, laboratory results including tumour markers (CEA, CA 72.4) and indirect signs as pleural effusion or ascites. Statistical Analysis Overall survival was assessed from the time of diagnosis of metastatic disease or tumour relapse. Time to progression (TTP) was assessed from the start of chemotherapy. Data are shown as median and range. Values were compared by the Mann-Whitney U test. A p value
