Quality of life of palliative chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction treated with irinotecan combined with 5-fluorouracil and folinic acid: results of a randomised phase III trial

Desmond Curran, Carmelo Pozzo, Jerzy Zaluski, Magdalena Dank, Carlo Barone, Vahur Valvere, Suayib Yalcin, Christian Peschel, Miklós Wenczl, Erdem Goker, Roland Bugat, Desmond Curran, Carmelo Pozzo, Jerzy Zaluski, Magdalena Dank, Carlo Barone, Vahur Valvere, Suayib Yalcin, Christian Peschel, Miklós Wenczl, Erdem Goker, Roland Bugat

Abstract

Purpose: The quality of life (QL) of advanced gastric cancer patients receiving irinotecan, folinic acid and 5-fluorouracil (5-FU) (IF arm) or cisplatin with 5-FU (CF arm) is presented.

Methods: Patients with measurable or evaluable advanced gastric cancer received IF weekly for 6/7 weeks or CF q4 weeks. QL was assessed using the EORTC QLQ-C30 at baseline, subsequently every 8 weeks until progression and thereafter every 3 months until death. The QL data were analysed using several statistical methods including summary measures and pattern-mixture modelling.

Results: A total of 333 patients were randomised and treated (IF 170, CF 163). The time-to-progression for IF and CF was 5.0 and 4.2 months (P = 0.088), respectively. The overall compliance rates for QL questionnaire completion were 60 and 56% in the IF and CF arms, respectively. Significant treatment differences were observed for the physical functioning scale (P = 0.024), nausea\vomiting (P = 0.001) and EQ-5D thermometer (P = 0.020) in favour of the IF treatment arm.

Conclusion: There was a trend in favour of IF over CF in time-to-progression. The IF group also demonstrated a better safety profile than CF and a better QL on a number of multi-item scales, suggesting that IF offers an alternative first-line platinum-free treatment option for advanced gastric cancer.

Figures

Fig. 1
Fig. 1
Plot of the least squares means estimates of the EORTC QLQ-C30 mean global health status by treatment group and dropout pattern. A higher score represents a better QL. Full green line represents pattern 4 (i.e. dropout after week 32). Other lines represent patterns 1–3, i.e. dropout at baseline, dropout at week 8 or 16, dropout at week 24 or 32, respectively
Fig. 2
Fig. 2
Testing the treatment effect using the delta method. EQ-5D HUI is on a different scale and consequently is not included in this figure

References

    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1002/(SICI)1097-0215(19990924)83:1<18::AID-IJC5>3.0.CO;2-M', 'is_inner': False, 'url': 'https://doi.org/10.1002/(sici)1097-0215(19990924)83:1<18::aid-ijc5>3.0.co;2-m'}, {'type': 'PubMed', 'value': '10449602', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/10449602/'}]}
    2. Pisani, P., Parkin, D. M., Bray, F., & Ferlay, J. (1999). Estimates of the worldwide mortality from 25 cancers in 1990. International Journal of Cancer,83(1), 18–29. doi:10.1002/(SICI)1097-0215(19990924)83:1<18::AID-IJC5>;2-M.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.3322/canjclin.55.1.10', 'is_inner': False, 'url': 'https://doi.org/10.3322/canjclin.55.1.10'}, {'type': 'PubMed', 'value': '15661684', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/15661684/'}]}
    2. Jemal, A., Murray, T., Ward, E., Samuels, A., Tiwari, R. C., Ghafoor, A., et al. (2005). Cancer statistics, 2005. CA: A Cancer Journal for Clinicians,55(1), 10–30. doi:10.3322/canjclin.55.1.10.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1097/00042737-200403000-00003', 'is_inner': False, 'url': 'https://doi.org/10.1097/00042737-200403000-00003'}, {'type': 'PubMed', 'value': '15195888', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/15195888/'}]}
    2. Dickson, J. L., & Cunningham, D. (2004). Systemic treatment of gastric cancer. European Journal of Gastroenterology and Hepatology,16(3), 255–263. doi:10.1097/00042737-200403000-00003.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '12810456', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/12810456/'}]}
    2. Bugat, R. (2003). Irinotecan in the treatment of gastric cancer. Annals of Oncology,14(Suppl 2), S37–S40.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1634/theoncologist.9-suppl_2-9', 'is_inner': False, 'url': 'https://doi.org/10.1634/theoncologist.9-suppl_2-9'}, {'type': 'PubMed', 'value': '15161986', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/15161986/'}]}
    2. Van Cutsem, E. (2004). The treatment of advanced gastric cancer: New findings on the activity of the taxanes. The Oncologist,9(Suppl 2), S9–S15.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1634/theoncologist.2008-0082', 'is_inner': False, 'url': 'https://doi.org/10.1634/theoncologist.2008-0082'}, {'type': 'PubMed', 'value': '18614586', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/18614586/'}]}
    2. Pozzo, C., & Barone, C. (2008). Is there an optimal chemotherapy regimen for the treatment of advanced gastric cancer that will provide a platform for the introduction of new biological agents? The Oncologist,13(7), 794–806. doi:10.1634/theoncologist.2008-0082.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1200/JCO.2005.05.0245', 'is_inner': False, 'url': 'https://doi.org/10.1200/jco.2005.05.0245'}, {'type': 'PubMed', 'value': '16782930', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/16782930/'}]}
    2. Wagner, A., Grothe, W., Haerting, J., Kleber, G., Grothey, A., & Fleig, W. E. (2006). Chemotherapy in advanced gastric cancer: A systematic review and meta-analysis based on aggregate data. Journal of Clinical Oncology,24(18), 2903–2909. doi:10.1200/JCO.2005.05.0245.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1200/JCO.2004.01.140', 'is_inner': False, 'url': 'https://doi.org/10.1200/jco.2004.01.140'}, {'type': 'PubMed', 'value': '15514373', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/15514373/'}]}
    2. Bouche, O., Raoul, J. L., Bonnetain, F., Giovannini, M., Etienne, P. L., Lledo, G., et al. (2004). Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: A Federation Francophone de Cancerologie Digestive Group Study—FFCD 9803. Journal of Clinical Oncology,22(21), 4319–4328. doi:10.1200/JCO.2004.01.140.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1200/JCO.2004.08.154', 'is_inner': False, 'url': 'https://doi.org/10.1200/jco.2004.08.154'}, {'type': 'PubMed', 'value': '15197201', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/15197201/'}]}
    2. Chau, I., Norman, A. R., Cunningham, D., Waters, J. S., Oates, J., & Ross, P. J. (2004). Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer-pooled analysis from three multicenter, randomized, controlled trials using individual patient data. Journal of Clinical Oncology,22(12), 2395–2403. doi:10.1200/JCO.2004.08.154.
    1. (1996). Outcomes of cancer treatment for technology assessment and cancer treatment guidelines: American Society of Clinical Oncology. Journal of Clinical Oncology, 14(2), 671–679.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '8996151', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/8996151/'}]}
    2. Webb, A., Cunningham, D., Scarffe, J. H., Harper, P., Norman, A., Joffe, J. K., et al. (1997). Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. Journal of Clinical Oncology,15(1), 261–267.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1200/JCO.2002.08.105', 'is_inner': False, 'url': 'https://doi.org/10.1200/jco.2002.08.105'}, {'type': 'PubMed', 'value': '11956258', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/11956258/'}]}
    2. Ross, P., Nicolson, M., Cunningham, D., Valle, J., Seymour, M., Harper, P., et al. (2002). Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) with epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. Journal of Clinical Oncology,20(8), 1996–2004. doi:10.1200/JCO.2002.08.105.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '11956251', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/11956251/'}]}
    2. Ilson, D. H. (2002). Epirubicin, cisplatin, and fluorouracil in gastric and esophageal cancer: A step ahead? Journal of Clinical Oncology,20(8), 1962–1964.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1200/JCO.2006.06.8429', 'is_inner': False, 'url': 'https://doi.org/10.1200/jco.2006.06.8429'}, {'type': 'PubMed', 'value': '17075117', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/17075117/'}]}
    2. Van Cutsem, E., Moiseyenko, V. M., 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 first-line therapy for advanced gastric cancer: A report of the V325 study group. Journal of Clinical Oncology,24(31), 4991–4997. doi:10.1200/JCO.2006.06.8429.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1200/JCO.2006.08.3956', 'is_inner': False, 'url': 'https://doi.org/10.1200/jco.2006.08.3956'}, {'type': 'PubMed', 'value': '17664468', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/17664468/'}]}
    2. Ajani, J. A., Moiseyenko, V. M., Tjulandin, S., Majlis, A., Constenla, M., Boni, X., et al. (2007). Quality of life with docetaxel plus cisplatin and fluorouracil compared with cisplatin and fluorouracil from a phase III trial for advanced gastric or gastroesophageal adenocarcinoma: The V-325 Study Group. Journal of Clinical Oncology,25(22), 3210–3216. doi:10.1200/JCO.2006.08.3956.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1023/A:1013129315036', 'is_inner': False, 'url': 'https://doi.org/10.1023/a:1013129315036'}, {'type': 'PubMed', 'value': '11822757', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/11822757/'}]}
    2. Blanke, C., Haller, D., Benson, A. B., Rothenberg, M. L., Berlin, J., Mori, M., et al. (2001). A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with previously untreated gastric adenocarcinoma. Annals of Oncology,12, 1575–1580. doi:10.1023/A:1013129315036.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '10458249', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/10458249/'}]}
    2. Boku, N., Ohtsu, A., Shimada, Y., Shirao, K., Seki, S., Saito, H., et al. (1999). Phase II study of a combination of irinotecan and cisplatin against metastatic gastric cancer. Journal of Clinical Oncology,17(1), 319–323.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '11099333', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/11099333/'}]}
    2. Ajani, J. A. (2000). Standard chemotherapy for gastric carcinoma: Is it a myth? Journal of Clinical Oncology,18(23), 4001–4003.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1038/sj.bjc.6602649', 'is_inner': False, 'url': 'https://doi.org/10.1038/sj.bjc.6602649'}, {'type': 'PMC', 'value': 'PMC2361806', 'is_inner': False, 'url': 'http://www.ncbi.nlm.nih.gov/pmc/articles/pmc2361806/'}, {'type': 'PubMed', 'value': '15942629', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/15942629/'}]}
    2. Moehler, M., Eimermacher, A., Siebler, J., Höhler, T., Wein, A., Menges, M., et al. (2005). Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer. British Journal of Cancer,92(12), 2122–2128. doi:10.1038/sj.bjc.6602649.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1093/annonc/mdh473', 'is_inner': False, 'url': 'https://doi.org/10.1093/annonc/mdh473'}, {'type': 'PubMed', 'value': '15550582', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/15550582/'}]}
    2. Pozzo, C., Barone, C., Szanto, J., Padi, E., Peschel, C., Bükki, J., et al. (2004). Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: Results of a randomized phase II study. Annals of Oncology,15(12), 1773–1781. doi:10.1093/annonc/mdh473.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1093/annonc/mdn166', 'is_inner': False, 'url': 'https://doi.org/10.1093/annonc/mdn166'}, {'type': 'PubMed', 'value': '18558665', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/18558665/'}]}
    2. Dank, M., Zaluski, J., Barone, C., Valvere, V., Yalcin, S., Peschel, C., et al. (2008). Randomized phase III study of irinotecan combined with 5-fluoruracil and folinic acid and cisplatin combined with 5-fluoruracil in palliative chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Annals of Oncology,19(8), 1450–1457. doi:10.1093/annonc/mdn166.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1080/10543409508835115', 'is_inner': False, 'url': 'https://doi.org/10.1080/10543409508835115'}, {'type': 'PubMed', 'value': '8580930', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/8580930/'}]}
    2. Morikawa, T., & Yoshida, M. (1995). A useful testing strategy in phase III trials: Combined test of superiority and test of equivalence. Journal of Biopharmaceutical Statistics,5(3), 297–306. doi:10.1080/10543409508835115.
    1. None
    2. Holm, S. (1979). A simple sequentially rejective multiple test procedure. Scandinavian Journal of Statistics,6, 65–70.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.2307/2529759', 'is_inner': False, 'url': 'https://doi.org/10.2307/2529759'}, {'type': 'PubMed', 'value': '963178', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/963178/'}]}
    2. Freedman, J., & White, S. J. (1976). On the use of Pocock and Simon’s method for balancing treatment numbers over prognostic factors in the controlled clinical trial. Biometrics,32, 691–694. doi:10.2307/2529759.
    1. None
    2. Fayers, P. M., Aaronson, N. K., Bjordal, K., Curran, D., & Groenvold, M. (1999). EORTC QLQ-C30 scoring manual (2nd ed.). Brussels: EORTC.
    1. None
    2. Kind, P. (1996). The EuroQL instrument: An index of health-related quality of life. In B. Spilker (Ed.), Quality of life and pharmacoeconomics in clinical trials (2nd ed., pp. 191–201). Philadelphia: Lippincott-Raven Publishers.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1002/(SICI)1097-0258(19980315/15)17:5/7<711::AID-SIM816>3.0.CO;2-H', 'is_inner': False, 'url': 'https://doi.org/10.1002/(sici)1097-0258(19980315/15)17:5/7<711::aid-sim816>3.0.co;2-h'}, {'type': 'PubMed', 'value': '9549818', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/9549818/'}]}
    2. Machin, D., & Weeden, S. (1998). Suggestions for the presentation of quality of life data from clinical trials. Statistics in Medicine,17(5–7), 711–724. doi:10.1002/(SICI)1097-0258(19980315/15)17:5/7<711::AID-SIM816>;2-H.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1002/(SICI)1097-0258(19980315/15)17:5/7<697::AID-SIM815>3.0.CO;2-Y', 'is_inner': False, 'url': 'https://doi.org/10.1002/(sici)1097-0258(19980315/15)17:5/7<697::aid-sim815>3.0.co;2-y'}, {'type': 'PubMed', 'value': '9549817', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/9549817/'}]}
    2. Curran, D., Molenberghs, G., Fayers, P. M., & Machin, D. (1998). Incomplete quality of life data in randomized trials: Missing forms. Statistics in Medicine,17(5–7), 697–709. doi:10.1002/(SICI)1097-0258(19980315/15)17:5/7<697::AID-SIM815>;2-Y.
    1. None
    2. Diggle, P. J., Liang, K. Y., & Zeger, S. L. (1994). Analysis of longitudinal data. Oxford: Clarendon Press.
    1. None
    2. Verbeke, G., & Molenberghs, G. (1997). Linear mixed models in practice. New York: Springer–Verlag.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1191/0962280202sm270ra', 'is_inner': False, 'url': 'https://doi.org/10.1191/0962280202sm270ra'}, {'type': 'PubMed', 'value': '11923994', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/11923994/'}]}
    2. Curran, D., Molenberghs, G., Aaronson, N. K., Fossa, S. D., & Sylvester, R. J. (2002). Analysing longitudinal continuous quality of life data with dropout. Statistical Methods in Medical Research,11(1), 5–23. doi:10.1191/0962280202sm270ra.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1200/JCO.2002.99.117', 'is_inner': False, 'url': 'https://doi.org/10.1200/jco.2002.99.117'}, {'type': 'PubMed', 'value': '12351614', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/12351614/'}]}
    2. Efficace, F., & Bottomley, A. (2002). Do quality-of-life randomized clinical trials support clinicians in their decision-making? Journal of Clinical Oncology,20(19), 4126. doi:10.1200/JCO.2002.99.117.
    1. Moehler, M., Trarbach, T., Seufferlein, T., Kubicka, S., Lordick, F., Geissler, M., et al. (2007). Cetuximab with irinotecan/Na-FA/5-FU as first-line treatment in advanced gastric cancer. European Journal of Cancer, 5(4), Abstract 3518.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1093/annonc/mdl459', 'is_inner': False, 'url': 'https://doi.org/10.1093/annonc/mdl459'}, {'type': 'PubMed', 'value': '17164226', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/17164226/'}]}
    2. Pinto, C., Di Fabio, F., Siena, S., Cascinu, S., Rojas Llimpe, F. L., et al. (2007). Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocancinoma (FOLCETUX study). Annals of Oncology,18(3), 510–517. doi:10.1093/annonc/mdl459.
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1200/JCO.2006.08.0887', 'is_inner': False, 'url': 'https://doi.org/10.1200/jco.2006.08.0887'}, {'type': 'PubMed', 'value': '17114652', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/17114652/'}]}
    2. Shah, M. A., Ramanathan, R. K., Ilson, D. H., Levnor, A., D'Adamo, D., O'Reilly, E., et al. (2006). Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. Journal of Clinical Oncology,24(33), 5201–5206.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel