Quality of life with biweekly docetaxel and capecitabine in advanced gastro-oesophageal cancer

Supportive Care in Cancer, Apr 2017

Purpose This study aimed to evaluate the feasibility and tolerability of biweekly docetaxel with capecitabine as first-line treatment in advanced gastro-oesophageal cancer. Methods Fifty-three patients at median age of 61 years with advanced gastric cancer were included in this prospective, non-randomized, multicentre phase II trial to receive intravenous docetaxel 50 mg/m2 on days 1 and 15, and oral capecitabine 1250 mg/m2 every 12 h, on days 1–7 and 15–21 of each 28-day cycle. QOL was assessed using EORTC QLQ-C30, together with the gastric module (QLQ-STO 22). Results Forty-six patients were evaluable for QOL analyses. No deterioration in global health status was found. Social functioning scores improved, and eating difficulties and pain were alleviated during treatment. The most common grade 3 or 4 toxicity was neutropenia (47%), whereas neutropenic fever was uncommon (6%). The clinical benefit rate was 60%, including complete and partial responses as well as stabilized disease. Median overall survival was 8.8 months (95% CI 5.8–11.9 months), and median time to progression was 6.2 months (95% CI 4.9–7.5 months). Conclusions Biweekly docetaxel with capecitabine is a feasible treatment in AGC, delivered on an outpatient basis, with no need for central venous access device. No deterioration of global health status was reported. In addition, pain and eating difficulties were alleviated during study treatment. This trial is registered at ClinicalTrials.​gov, number NCT00669370.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

http://link.springer.com/content/pdf/10.1007%2Fs00520-017-3689-5.pdf

Quality of life with biweekly docetaxel and capecitabine in advanced gastro-oesophageal cancer

Quality of life with biweekly docetaxel and capecitabine in advanced gastro-oesophageal cancer E. A. Korkeila 0 1 2 3 4 T. Salminen 0 1 2 3 4 R. Kallio 0 1 2 3 4 M. Mikkola 0 1 2 3 4 P. Auvinen 0 1 2 3 4 S. Pyrhönen 0 1 2 3 4 R. Ristamäki 0 1 2 3 4 0 Department of Oncology and Haematology, Oulu University and Oulu University Hospital , Oulu , Finland 1 Department of Oncology, Tampere University and Tampere University Hospital , Tampere , Finland 2 Department of Oncology, University of Turku and Turku University Hospital , Hämeentie 11, PB 52, FI-20521 Turku , Finland 3 Faculty of Medicine and Cancer Center and Department of Oncology, University of Eastern Finland, Kuopio University Hospital , Kuopio , Finland 4 Department of Oncology, Vaasa Central Hospital , Vaasa , Finland Purpose This study aimed to evaluate the feasibility and tolerability of biweekly docetaxel with capecitabine as first-line treatment in advanced gastro-oesophageal cancer. Methods Fifty-three patients at median age of 61 years with advanced gastric cancer were included in this prospective, non-randomized, multicentre phase II trial to receive intravenous docetaxel 50 mg/m2 on days 1 and 15, and oral capecitabine 1250 mg/m2 every 12 h, on days 1-7 and 15-21 of each 28-day cycle. QOL was assessed using EORTC QLQ-C30, together with the gastric module (QLQ-STO 22). Results Forty-six patients were evaluable for QOL analyses. No deterioration in global health status was found. Social functioning scores improved, and eating difficulties and pain were alleviated during treatment. The most common grade 3 or 4 toxicity was neutropenia (47%), whereas neutropenic fever was uncommon (6%). The clinical benefit rate was 60%, including complete and partial responses as well as stabilized disease. Median overall survival was 8.8 months (95% CI 5.8-11.9 months), and median time to progression was 6.2 months (95% CI 4.9-7.5 months). Conclusions Biweekly docetaxel with capecitabine is a feasible treatment in AGC, delivered on an outpatient basis, with no need for central venous access device. No deterioration of global health status was reported. In addition, pain and eating difficulties were alleviated during study treatment. This trial is registered at ClinicalTrials.gov, number NCT00669370. Quality of life; Advanced gastro-oesophageal cancer; Chemotherapy; Palliative treatment - The incidence of distal gastric cancer is decreasing, whereas cancers of the distal oesophagus and gastro-oesophageal junction tend to increase in the Western world [1]. Worldwide, these cancers cause substantial morbidity and mortality. Nearly one million new cases and more than 700,000 deaths due to gastric cancer were estimated to have occurred in 2012, setting gastric cancer the fifth most common cancer and the third most common cause of cancer death [2]. The prognosis of advanced gastro-oesophageal cancer (AGC) remains poor [1, 2]. A substantial proportion of patients presents with or ends up having metastatic disease after initial treatment [3, 4]. Systemic chemotherapy is shown to improve disease outcome in AGC, as compared to best supportive care, with median survival rates reaching 6–9 months [5–7]. During the past decade, several new-generation cytotoxic agents, including capecitabine, irinotecan, oxaliplatin and docetaxel, have been investigated in the treatment of metastatic gastric cancer [7–10]. Two previous large phase III trials demonstrated an oral fluoropyrimidine capecitabine not to be inferior to 5-FU in the setting of a platinum-containing doublet or triplet for AGC [8, 9]. Adding docetaxel into the combination of cisplatin and fluorouracil (DCF) was studied in a randomized phase III trial in first-line therapy for AGC. The final results showed improved survival, response rate, and health-related QOL, albeit increased toxicity with DCF [10]. Further, in a phase III open-label, randomized controlled trial in HER2-positive AGC, trastuzumab in combination with chemotherapy significantly improved median overall survival as compared to chemotherapy alone [11]. Recently, VEGFR-2 antagonist ramucirumab was found to improve survival as monotherapy or in combination with paclitaxel in AGC after first-line treatment [12, 13]. However, so far, no survival benefit has been reported in the first-line setting with other novel targeted agents in AGC, in addition of trastuzumab. In advanced cancer, the primary treatment goals are to prolong survival, relieve symptoms and sustain or improve the quality of life. Thereby, chemotherapy-related toxicity is an important issue when determining the true value of treatment. Patients with AGC are generally elderly and exhibit poor general performance status, which emphasizes the need for effective treatment options and improved control of side effects. On the basis of these considerations, we conducted a phase II trial to determine the feasibility and tolerability of biweekly docetaxel in combination with capecitabine as first-line treatment of patients with AGC. Patients and methods Study design and patient population This prospective, non-randomized, multicentre phase II trial included patients over 18 years of age with histologically confirmed, locally advanced (inoperable) or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Disease lesions could be either evaluable or measurable. No previous chemotherapy for advanced or metastatic disease was allowed, and a time interval of ≥6 months after adjuvant chemotherapy was imperative. Patients were required to have adequate haematological (neutrophils >1.5 × 109/l, haemoglobin ≥100 g/l after transfusion when needed and platelets ≥100 × 109/l), renal (serum creatinine ≤1.25 × upper normal limit) and liver function (total serum bilirubin ≤1.25 × upper normal limit or alanine aminotransferase ≤3 × upper normal limit, alkaline phosphatase ≤2.5 × upper normal limit, unless bone metastases; in case of liver metastasis total serum bilirubin ≤1.5 × upper normal limit and alanine aminotransferase ≤5 × upper normal limit). Prophylactic use of granulocyte colony-stimulating factor (G-CSF) was not allowed. Exclusion criteria included pregnancy or breast feeding, metastatic disease to the central nervous system, unresolved bowel obstruction or dysmotility, chronic diarrhoea, clinically significant malabsorption syndrome, inability to swallow tablets, known dihydropyrimidine dehydrogenase deficiency, peripheral neuropathy ≥grade 2, concurrent severe and/or uncontrolled co-morbid medical condition such as uncontrolled infection, hypertension, ischemic heart disease, myocardial infarction within previous 6 months or congestive heart disease. Patients with previous serious hypersensitive reactions, history of allergy to drugs containing the excipient TWEEN 80® or 5-fluorouracil, major surgery within 4 weeks prior to study treatment or passage disorder were also excluded from the participation in the study. Patients received intravenous docetaxel 50 mg/m2 on days 1 and 15 and oral capecitabine 1250 mg/m2 every 12 h, starting on days 1 and 15 in the evening and continuing on days 2–7 and 16–21. One cycle consisted of 28 days. Premedication with 7.5 mg of oral dexamethasone or methylprednisolone 40 mg was given the evening prior to docetaxel infusion and continuing thereafter every 12 h three times. Dose reduction was based on the most severe grade of toxicity in the previous cycle. A planned cycle could be delayed up to 21 days due to toxicity. If a patient had not recovered from toxicities within 21 days, he/she was withdrawn from the study. In case either Patient characteristics (n = 53) of the test docetaxel or capecitabine was discontinued due to an adverse event, the patient could continue in the study taking only one test drug. Efficacy and safety assessments Before study inclusion, patients underwent complete physical examination, blood analysis (haematology and biochemistry), electrocardiogram and computerized tomography (CT) scan of the abdomen and pelvis as well as CT of the thorax or chest x-ray. Blood samples were taken for haematology tests prior to each treatment on days 1 and 15 of each cycle. Biochemistry tests were performed before the start of each cycle. During treatment, imaging of target and non-target lesions was repeated every three cycles (every 12 weeks) or as clinically indicated. Tumour response was classified according to RECIST [14].Toxicity was evaluated before every cycle using National Cancer Institute-Common Terminology Criteria for Adverse Events [15]. Quality of life assessments Quality of life (QOL) was assessed using European Organization for Research and Treatment of Cancer Qualityof-Life Questionnaire (EORTC QLQ-C30) [16], together with the gastric module (QLQ-STO 22) [17]. QLQ assessment was performed at baseline, on day 1 of the second and subsequent The main results of QoL-C30 and STO-22 questionnaires cycles (prior to the infusion), at the end-of-study visit, during follow-up until progression or the start of second-line treatment or death. Prerequisites for inclusion in the analyses of (a change in) physical functioning score consisted of at least one given treatment cycle as well as QLQ-questionnaire filled at baseline and after the first treatment cycle. The physical functioning score was measured using the EORTC QLQ-C30 and QLQ-STO 22 [16, 17]. Statistical analysis The primary end point of the study was physical functioning score, measured by the EORTC QLQ-C30 and QLQ-STO 22 instruments, comparing the scores received at baseline with those obtained after one treatment cycle, using a paired t test. Secondary end points were time to progression (TTP), overall response rate (ORR) and overall survival (OS). Summary measurements are presented as mean and standard deviation (SD) or as median with 25th–75th percentile, unless otherwise stated. The change from baseline for continuous variables was analysed by paired samples t test. The Kaplan-Meier curve was created to show overall survival from recruitment to the end of follow-up (i.e. death or end of the study). All analyses were performed using SPSS for Windows (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, version 20.0. Armonk, NY: IBM Corp.) Global health status Baseline n = 46 Cycle 1 n = 45 Cycle 2 n = 37 Cycle 3 n = 30 Cycle 4 n = 27 Cycle 5 n = 20 The values are presented as mean with standard deviation (SD). The scores of each cycle as compared to the baseline score Results Patients and treatment This prospective phase II trial was conducted at four university hospitals and one central hospital in Finland. A total of 53 patients were registered between June 2006 and December 2009. One patient was withdrawn from the study after the first cycle due to detected HER2-positivity, necessitating the start of trastuzumab treatment. Altogether, 46 patients were eligible for the QOL analyses. The patient characteristics are summarized in Table 1. The total number of chemotherapy cycles administered was 220. The median number of treatment cycles per patient was 4 (range, 0.5–16), and the median time on study treatment was 4.8 months (range, 0.1–17.6 months). The main reasons for treatment discontinuation were progressive disease or deteriorating general condition (n = 31, 58%). Altogether, 26 patients (49%) received second-line chemotherapy. Effect of treatment on quality of life The number of patients with assessable QOL questionnaires at baseline was 46 (45 for global health status and STO 22 questionnaires), after the first and subsequent four cycles, the number of patients was 45, 37, 30, 27 and 20, respectively. Detailed results QOL analyses are shown in Table 2. Pain and eating restrictions were common at baseline (Fig. 1a). During treatment, clinically relevant alleviation was detected both in pain and in eating restrictions. No deterioration in global health status or in social or physical functioning occurred (Fig. 1a–c). One of the 53 patients (2%) achieved complete response (CR), and 8 patients (15%) had partial response (PR). Of the patients, 23 (43%) showed stable disease (SD) and 5 (9%) had progressive disease (PD). The clinical benefit rate was 60%. The response was not evaluable among 18 patients (30%), due to early discontinuation of the study treatment. Median time to progression was 6.2 months (95% CI 4.9–7.5 months) and median overall survival 8.8 months (95% CI 5.8–11.9 months) (Fig. 2a, b). During study treatment, 25 (47%) patients were hospitalized. Fifty percent of the hospitalizations were caused by a treatment-related adverse event. The most common grade 3 or 4 toxicity was neutropenia, detected in 25 patients (47%). However, only three patients (6%) experienced neutropenic fever. One patient had a Global health status n = 45 n = 46 Social function Physical function STO22 Pain STO22 Eating restriction n = 45 45 37 30 27 20 Fig. 1 Effect of treatment on quality of life: a global health status, b social and physical function, and c pain and eating restrictions presented as mean values per cycle grade 3 allergic reaction during docetaxel infusion, precluding further treatment. There were no direct treatment-related deaths. One sudden death occurred during the first treatment cycle. According to the autopsy report, the cause of death was metastatic gastric cancer and no evidence of cardiac-related death could be detected. The common adverse events are listed in Table 3. This prospective phase II trial with a combination of biweekly docetaxel and capecitabine in AGC showed no deterioration of global health status or either physical or social functioning. Importantly, the patients’ quality of life was not compromised during treatment. Moreover, disease-associated symptoms, including eating restrictions and dysphagia, as well as pain and anxiety, were alleviated during study treatment. The regimen was also conveniently delivered on an outpatient setting without a need for central venous access device. Docetaxel in various combinations has previously been studied in the treatment in AGC, also including QOL assessments [18–21]. A recent prostate cancer trial reported better time to treatment failure and fewer serious adverse events with two weekly than with three weekly dosing of docetaxel [22]. Adverse events, according to grade In AGC, docetaxel combined to cisplatin and fluorouracil resulted in better symptom palliation and improved QOL, as compared to treatment with epirubicin, cisplatin and fluorouracil. Unfortunately, treatment toxicity data for this combination were not readily provided [19]. Previous trials have generally demonstrated improved QOL accompanied with improved efficacy in AGC, despite increased toxicity with docetaxel triplet combinations [10, 18, 19, 21], i.e. treatment efficacy rather than toxicity tends to affect QOL [23]. Importantly, in the current study, the patients’ QOL was not compromised during treatment. Eating difficulties were alleviated during chemotherapy but started deteriorating along with disease progression. Similarly, after commencing therapy, pain was experienced to relieve but intensify again as cancer progressed. Physical functioning remained stable during chemotherapy, while social functioning improved, even despite disease progression. The global health status was maintained or slightly improved during therapy. Gubanski and colleagues investigated the effect of sequential treatment on QOL. Patients were randomized to start treatment with either docetaxel or irinotecan combined to fluorouracil and leucovorin. After four cycles, the treatment was switched. Chemotherapy was not found to affect the average QOL scores. Instead, patients with a radiological response were able to sustain better QOL as compared to patients with no radiological response [24]. A patient’s perception of expected treatment efficacy might also influence on QOL scores: a substantial proportion of patients may not comprehend their disease unlikely to be curable [25]. Thus, they may be ready to tolerate even serious side effects and yet experience QOL to be maintained. The results of this study showed the clinical benefit rate to be 60%, including complete (CR) and partial (PR) responses and stabilized disease (SD), and median overall survival of 8.8 months. These findings are parallel to a previous trial of weekly docetaxel together with capecitabine on days 1–14 of a 21-day cycle, showing a comparable response rate of 29%, stable disease of 44% and overall survival reaching 10.7 months [26]. Another study investigating dose-dependent efficacy of docetaxel and capecitabine resulted in improved overall response rates with full dosing of these agents. However, two patients in each cohort experienced grade 3–4 cardiac arrhythmia, one patient pulmonary oedema, and three patients grade 3– 4 thrombosis/pulmonary embolism, one of them leading to death [27]. In the current study, no death was directly associated to study treatment. One patient died after the very first infusion of chemotherapy due to rapidly progressing cancer, without any signs of cardiac complications in the autopsy. However, ventricular fibrillation cannot entirely be ruled out, despite of a negative autopsy report. In the current study, only one patient experienced grade 3–4 cardiac arrhythmia. Our study shows a moderate incidence of grade 3–4 neutropenia, resulting only rarely in neutropenic fever. Nevertheless, infection was the main reason for treatment-related hospitalization. These results are comparable with earlier studies, reporting even higher rates of grade 3–4 neutropenia, in up to 23–80% of patients, febrile neutropenia among 2–12% and grade 3–4 nonneutropenic fever among 2–41% of patients, while hospitalization data are not readily available [19, 26, 27]. The incidence of mild palmo-plantar dysesthesia or hand-foot syndrome (HFS) was previously reported to be 9–42% and that of severe HFS 3– 20% [19, 26, 27]. Even though the incidence of HFS in the current study was 45%, no grade 3–4 symptoms were detected. Likewise, mild diarrhoea was frequent but severe diarrhoea a rare event. On the whole, haematologic and non-haematologic toxicities were considered tolerable. In conclusion, no treatment combination has been proven superior as compared to others in AGC in the palliative setting. Biweekly docetaxel, together with capecitabine is a feasible, outpatient-based, well-tolerated treatment that enables sustaining QOL and alleviating disease-associated symptoms. Acknowledgements This study was partly supported by a grant from Sanofi Genzyme. We are thankful to Aura Arola, M.D, for collecting data, Pasi Ohtonen M.A, Biostatistician, for his help with the statistical analyses and Kaisa-Mari Paananen, Key Account Manager, Sanofi Genzyme, for her continuous support and encouragement during this study. Compliance with ethical standards Ethical approval This study was conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The protocol was approved by the Ethics Committee of the Hospital District of Southwest Finland and by Finnish Medicines Agency (Fimea). The study was registered in www. clinicaltrials.gov (NCT00669370). Informed consent All patients provided written informed consent before the study entry. Open Access This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http:// creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 1. Jézéquel J , Bessaguet C , Verveur C , Faycal J , Richert Z , Metges JP et al ( 2010 ) Trends in incidence, management, and survival of gastric and cardia carcinomas in the area of Finistere (France) between 1984 and 2003 . Eur J Gastroenterol Hepatol 22 : 1412 - 1419 2. Ferlay J , Soerjomataram I , Rajesh D , Forman D , Mathers C , Rebelo M et al ( 2015 ) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012 . Int J Cancer 136 : E359 - E386 3. National Cancer Institute . SEER database . http://seer.cancer.gov/ statfacts/html/stomach.html. Accessed 18 .11. 2013 . 4. Cunningham D , Allum WH , Stenning SP , Thompson JN , Van der Velde CJ , Nicolson M et al ( 2006 ) For the MAGIC trial participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer . N Engl J Med 355 : 11 - 20 5. Pyrhönen S , Kuitunen T , Nyandoto P , Kouri M ( 1995 ) Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer . Br J Cancer 71 : 587 - 591 6. Glimelius B , Ekström K , Hoffman K , Graf W , Sjöden PO , Haglund U et al ( 1997 ) Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer . Ann Oncol 8 : 163 - 168 7. Wagner AD , Grothe W , Haerting J , Kleber G , Grothey A , Fleigh WE et al ( 2006 ) Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data . J Clin Oncol 24 : 2903 - 2909 8. Cunningham D , Starling N , Rao S , Iveson T , Nicolson M , Coxon F et al ( 2008 ) Capecitabine and oxaliplatin for advanced esophagogastric cancer . N Engl J Med 358 : 36 - 46 9. Kang YK , Kang WK , Shin DB , Chen J , Xiong J , Wang J et al ( 2009 ) Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomized phase III noninferiority trial . Ann Oncol 20 : 666 - 673 10. Van Cutsem E , Moiseyenko VM , Tjulandin S , Majlis A , Constenla M , Boni C et al ( 2006 ) Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as firstline therapy for advanced gastric cancer: a report of the V325 study group . J Clin Oncol 24 : 4991 - 4997 11. Bang YJ , Van Cutsem E , Feyereislova A , Chung HC , Shen L , Sawaki A et al ( 2010 ) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial . Lancet 376 : 687 - 697 12. Fuchs CS , Tomasek J , Yong CJ , Dumitru F , Passalacqua R , Goswami C et al ( 2014 ) Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial . Lancet 383 : 31 - 39 13. Wilke H , Muro K , Van Cutsem E , Sang-Cheul O , Bodoky G , Shimada Y et al ( 2014 ) Ramucirumab plus paclitaxel in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial . Lancet Oncol 15 : 1224 - 1230 14. Therasse P , Arbuck SG , Eisenhauer EA , Wanders RSK , Rubinstein L , Verweij J et al ( 2000 ) New guidelines to evaluate the response to treatment in solid tumors . J Natl Cancer Inst 92 : 205 - 216 15. National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE Version 2 .0. http://www.eortc.be/ services/doc/ctc/ctcv20_4- 30 -992.pdf. Accessed 18 .11. 2013 . 16. Aaronson NK , Ahmedzai S , Bergman B , Bullinger M , Cull A , Duez NJ et al ( 1993 ) For the European Organization for Research and Treatment of Cancer Study Group of Quality of Life. The European Organization of Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology . J Natl Cancer Inst 85 : 365 - 376 17. Blazeby JM , Conroy T , Bottomley A , Vickery C , Arraras J , Sezer Q et al ( 2004 ) European Organisation for Research and Treatment of Cancer Gastrointestinal and Quality of Life Groups. Clinical and psychometric validation of a questionnaire module, the EORTC QOQ-STO 22, to assess quality of life in patients with gastric cancer . Eur J Cancer 40 : 2260 - 2268 18. Sadighi S , Mohagheghi MA , Montazeri A , Sadighi Z ( 2006 ) Quality of life in patients with advanced gastric cancer: a randomized trial comparing docetaxel , cisplatin, 5 - FU (TCF) with epirubicin, cisplatin, 5 - FU (ECF). BMC Cancer 6:274 19. Roth AD , Fazio N , Stupp R , Falk S , Bernhard J , Saletti P ( 2007 ) Docetaxel, cisplatin, and fluorouracil; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II Trail of the Swiss Group for Clinical Cancer Research . J Clin Oncol 25 : 3217 - 3223 20. Kripp M , Al-Batran SE , Rosowski J , Pauligh C , Homann N , Hartmann JT et al ( 2014 ) Quality of life of older patients receiving docetaxel-based chemotherapy triplets for esophagogastric adenocarcinoma: a randomized study of the Arbeitsgemeinschaft Internistische Onkologie (AIO) . Gastric Cancer 17 : 181 - 187 21. Ajani JA ( 2008 ) Optimizing docetaxel chemotherapy in patients with cancer of the gastric and gastroesophageal junction . Cancer 113 : 945 - 955 22. Kellokumpu-Lehtinen P , Harmenberg U , Joensuu T , McDermott R , Hervonen P , Ginmann C et al ( 2013 ) 2-Weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial . Lancet Oncol 14 : 117 - 124 23. Al-Batran SE , Ajani JA ( 2010 ) Impact of chemotherapy on quality of life in patients with metastatic esophagogastric cancer . Cancer 116 : 2511 - 2518 24. Gubanski M , Glimelius B , Lind PA ( 2014 ) Quality of life in patients with advanced gastric cancer sequentially treated with docetaxel and irinotecan with 5-fluorouracil and folinic acid (leucovorin) . Med Oncol 31 : 906 25. Weeks JC , Catalano PJ , Cronin A , Finkelman MD , Mack JW , Keating NL et al ( 2012 ) Patients' expectations about effects of chemotherapy for advanced cancer . N Engl Med 367 : 2012 26. Lo SS , Khorana AA , Javle M , Simon S , Kiefer G , Rajasenan K et al ( 2010 ) A phase II study of weekly docetaxel in combination with capecitabine in advanced gastric and gastroesophageal adenocarcinomas . Oncology 78 : 125 - 129 27. Thuss-Patience PC , Kretzschmar A , Dogan Y , Rothmann F , Blau I , Schwaner I et al ( 2011 ) Docetaxel and capecitabine for advanced gastric cancer: investigating dose-dependent efficacy in two patient cohorts . Br J Cancer 105 : 505 - 512


This is a preview of a remote PDF: http://link.springer.com/content/pdf/10.1007%2Fs00520-017-3689-5.pdf

E. A. Korkeila, T. Salminen, R. Kallio, M. Mikkola, P. Auvinen, S. Pyrhönen, R. Ristamäki. Quality of life with biweekly docetaxel and capecitabine in advanced gastro-oesophageal cancer, Supportive Care in Cancer, 2017, DOI: 10.1007/s00520-017-3689-5